Trial Outcomes & Findings for Study of the Molecular Features of Postmenopausal Women With HR+ HER2-negative aBC on First-line Treatment With Ribociclib and Letrozole and, in Patients With a PIK3CA Mutation, on Second-line Treatment With Alpelisib Plus Fulvestrant (NCT NCT03439046)
NCT ID: NCT03439046
Last Updated: 2026-07-10
Results Overview
PFS: Time (months) from start of the study treatment to first documented progression or death due to any cause, whichever came first. Kaplan-Meier estimates. Persistent Wild Type: Wild Type (or single nucleotide polymorphisms \[SNPs\] only) at screening without hotspot mutations at any later assessment. Confirmed cleared: Mutated, with 100% decrease in target mutation variant allele frequency (VAF) at C1D15 or at C2D1 also observed at FI. Unconfirmed cleared: Mutated that cleared or at C1D15 or at C2D1 that were not cleared at FI. Late cleared: Mutated without 100% decrease in target mutation VAF at C1D15 and at C2D1 with 100% decrease in target mutation VAF at FI. New mutated: Wild Type ( \[SNPs\] only) at screening with hotspot mutations at C1D15 or C2D1. Late mutated: Wild Type patients (or SNPs only) at screening without hotspot mutations at C1D15 and C2D1 with hotspot mutations at FI. Confirmed mutated: Mutated without 100% decrease in target mutation VAF at any later assessment.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
287 participants
Primary outcome timeframe
Up to approximately 5.7 years
Results posted on
2026-07-10
Participant Flow
All inclusion and exclusion criteria were checked at screening.
Participant milestones
| Measure |
Ribociclib+Letrozole (Core Phase)
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Core Phase
STARTED
|
287
|
0
|
|
Core Phase
COMPLETED
|
184
|
0
|
|
Core Phase
NOT COMPLETED
|
103
|
0
|
|
Extension Phase
STARTED
|
0
|
21
|
|
Extension Phase
COMPLETED
|
0
|
16
|
|
Extension Phase
NOT COMPLETED
|
0
|
5
|
Reasons for withdrawal
| Measure |
Ribociclib+Letrozole (Core Phase)
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Core Phase
Death
|
27
|
0
|
|
Core Phase
Lost to Follow-up
|
14
|
0
|
|
Core Phase
Other
|
2
|
0
|
|
Core Phase
Study terminated by sponsor
|
45
|
0
|
|
Core Phase
Subject/guardian decision
|
15
|
0
|
|
Extension Phase
Death
|
0
|
3
|
|
Extension Phase
Lost to Follow-up
|
0
|
1
|
|
Extension Phase
Subject/guardian decision
|
0
|
1
|
Baseline Characteristics
Study of the Molecular Features of Postmenopausal Women With HR+ HER2-negative aBC on First-line Treatment With Ribociclib and Letrozole and, in Patients With a PIK3CA Mutation, on Second-line Treatment With Alpelisib Plus Fulvestrant
Baseline characteristics by cohort
| Measure |
Ribociclib+Letrozole (Core Phase)
n=287 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
|---|---|
|
Age, Customized
12 years - <18 years
|
0 participants
n=9 Participants
|
|
Age, Customized
18 years - <65 years
|
125 participants
n=9 Participants
|
|
Age, Continuous
|
65.5 years
STANDARD_DEVIATION 8.39 • n=9 Participants
|
|
Age, Customized
in utero
|
0 participants
n=9 Participants
|
|
Age, Customized
Preterm newborns infants
|
0 participants
n=9 Participants
|
|
Age, Customized
0 - <28 days
|
0 participants
n=9 Participants
|
|
Age, Customized
28 days - <2 years
|
0 participants
n=9 Participants
|
|
Age, Customized
2 years - <12 years
|
0 participants
n=9 Participants
|
|
Age, Customized
65 years - <85 years
|
161 participants
n=9 Participants
|
|
Age, Customized
>=85 years
|
1 participants
n=9 Participants
|
|
Sex: Female, Male
Female
|
287 Participants
n=9 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=9 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
280 participants
n=9 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=9 Participants
|
|
Race/Ethnicity, Customized
Unknown Race
|
5 participants
n=9 Participants
|
|
Race/Ethnicity, Customized
Other Race
|
1 participants
n=9 Participants
|
PRIMARY outcome
Timeframe: Up to approximately 5.7 yearsPopulation: The biomarker analysis set (BAS) included participants who received at least one dose of either ribociclib or letrozole and who had an evaluable biomarker profile (i.e., both valid liquid biopsy and TK1 serum samples collected at screening) and who did not have violations of the main inclusion-exclusion criteria. Data are reported only for participants who had a valid sample at screening, Cycle 1 Day 15, Cycle 2 Day 1, and at the first imaging evaluation. Each cycle was 28 days.
PFS: Time (months) from start of the study treatment to first documented progression or death due to any cause, whichever came first. Kaplan-Meier estimates. Persistent Wild Type: Wild Type (or single nucleotide polymorphisms \[SNPs\] only) at screening without hotspot mutations at any later assessment. Confirmed cleared: Mutated, with 100% decrease in target mutation variant allele frequency (VAF) at C1D15 or at C2D1 also observed at FI. Unconfirmed cleared: Mutated that cleared or at C1D15 or at C2D1 that were not cleared at FI. Late cleared: Mutated without 100% decrease in target mutation VAF at C1D15 and at C2D1 with 100% decrease in target mutation VAF at FI. New mutated: Wild Type ( \[SNPs\] only) at screening with hotspot mutations at C1D15 or C2D1. Late mutated: Wild Type patients (or SNPs only) at screening without hotspot mutations at C1D15 and C2D1 with hotspot mutations at FI. Confirmed mutated: Mutated without 100% decrease in target mutation VAF at any later assessment.
Outcome measures
| Measure |
Ribociclib+Letrozole (Core Phase)
n=187 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Progression-Free Survival (PFS) by Cycle 1 Day 15 Complete Mutational Dynamic Change
Confirmed Cleared n=46
|
22.44 months
Interval 15.93 to 32.23
|
—
|
|
Progression-Free Survival (PFS) by Cycle 1 Day 15 Complete Mutational Dynamic Change
Unconfirmed Cleared n=8
|
10.22 months
Interval 2.69 to
The upper limit of 95% CI was not estimable due to an insufficient number of participants with events.
|
—
|
|
Progression-Free Survival (PFS) by Cycle 1 Day 15 Complete Mutational Dynamic Change
Persistent Wild Type n=76
|
55.82 months
Interval 39.06 to
The upper limit of 95% CI was not estimable due to an insufficient number of participants with events.
|
—
|
|
Progression-Free Survival (PFS) by Cycle 1 Day 15 Complete Mutational Dynamic Change
New Mutated n=19
|
16.53 months
Interval 9.03 to 45.9
|
—
|
|
Progression-Free Survival (PFS) by Cycle 1 Day 15 Complete Mutational Dynamic Change
Late Mutated n=8
|
15.67 months
Interval 2.0 to 21.42
|
—
|
|
Progression-Free Survival (PFS) by Cycle 1 Day 15 Complete Mutational Dynamic Change
Late Cleared n=12
|
11.07 months
Interval 3.29 to 19.09
|
—
|
|
Progression-Free Survival (PFS) by Cycle 1 Day 15 Complete Mutational Dynamic Change
Confirmed Mutated n=18
|
14.32 months
Interval 2.89 to 44.22
|
—
|
PRIMARY outcome
Timeframe: Up to approximately 5.7 yearsPopulation: The biomarker analysis set (BAS) included participants who received at least one dose of either ribociclib or letrozole and who had an evaluable biomarker profile (i.e., both valid liquid biopsy and TK1 serum samples collected at screening) and who did not have violations of the main inclusion-exclusion criteria. Data are reported only for participants who had a valid sample at screening, Cycle 1 Day 15, Cycle 2 Day 1, and at the first imaging evaluation. Each cycle was 28 days.
Kaplan-Meier estimates. Persistent Wild Type: Wild Type (or single nucleotide polymorphisms \[SNPs\] only) at screening without hotspot mutations at any later assessment. Confirmed cleared: Mutated, with 100% decrease in target mutation variant allele frequency (VAF) at C1D15 or at C2D1 also observed at FI. Unconfirmed cleared: Mutated that cleared or at C1D15 or at C2D1 that were not cleared at FI. Late cleared: Mutated without 100% decrease in target mutation VAF at C1D15 and at C2D1 with 100% decrease in target mutation VAF at FI. New mutated: Wild Type ( \[SNPs\] only) at screening with hotspot mutations at C1D15 or C2D1. Late mutated: Wild Type patients (or SNPs only) at screening without hotspot mutations at C1D15 and C2D1 with hotspot mutations at FI. Confirmed mutated: Mutated without 100% decrease in target mutation VAF at any later assessment.
Outcome measures
| Measure |
Ribociclib+Letrozole (Core Phase)
n=187 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Number of Participants With Progression-Free Survival (PFS) Events by Cycle 1 Day 15 Complete Mutational Dynamic Change
New Mutated n=19
|
13 participants
|
—
|
|
Number of Participants With Progression-Free Survival (PFS) Events by Cycle 1 Day 15 Complete Mutational Dynamic Change
Persistent Wild Type n=76
|
31 participants
|
—
|
|
Number of Participants With Progression-Free Survival (PFS) Events by Cycle 1 Day 15 Complete Mutational Dynamic Change
Late Mutated n=8
|
6 participants
|
—
|
|
Number of Participants With Progression-Free Survival (PFS) Events by Cycle 1 Day 15 Complete Mutational Dynamic Change
Confirmed Cleared n=46
|
28 participants
|
—
|
|
Number of Participants With Progression-Free Survival (PFS) Events by Cycle 1 Day 15 Complete Mutational Dynamic Change
Unconfirmed Cleared n=8
|
6 participants
|
—
|
|
Number of Participants With Progression-Free Survival (PFS) Events by Cycle 1 Day 15 Complete Mutational Dynamic Change
Late Cleared n=12
|
10 participants
|
—
|
|
Number of Participants With Progression-Free Survival (PFS) Events by Cycle 1 Day 15 Complete Mutational Dynamic Change
Confirmed Mutated n=18
|
12 participants
|
—
|
PRIMARY outcome
Timeframe: Up to approximately 5.7 yearsPopulation: The biomarker analysis set (BAS) included participants who received at least one dose of either ribociclib or letrozole and who had an evaluable biomarker profile (i.e., both valid liquid biopsy and TK1 serum samples collected at screening) and who did not have violations of the main inclusion-exclusion criteria.
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. The data row labels below refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Outcome measures
| Measure |
Ribociclib+Letrozole (Core Phase)
n=263 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
Two at First Imaging Evaluation n=206
|
11 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
Two at End of Study Treatment due to PD n=118
|
21 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
Two at End of Study Treatment due to Other n=39
|
2 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
Three or More at Screening n=263
|
16 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
None at Screening n=263
|
145 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
None at Cycle 1 Day 15 n=238
|
152 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
None at Cycle 2 Day 1 n=242
|
160 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
None at First Imaging Evaluation n=206
|
147 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
None at End of Study Treatment due to PD n=118
|
50 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
None at End of Study Treatment due to Other n=39
|
27 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
One at Screening n=263
|
70 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
One at Cycle 1 Day 15 n=238
|
51 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
One at Cycle 2 Day 1 n=242
|
53 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
One at First Imaging Evaluation n=206
|
40 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
One at End of Study Treatment due to PD n=118
|
26 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
One at End of Study Treatment due to Other n=39
|
10 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
Two at Screening n=263
|
32 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
Two at Cycle 1 Day 15 n=238
|
28 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
Two at Cycle 2 Day 1 n=242
|
21 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
Three or More at Cycle 1 Day 15 n=238
|
7 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
Three or More at Cycle 2 Day 1 n=242
|
8 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
Three or More at First Imaging Evaluation n=206
|
8 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
Three or More at End of Study Treatment due to PD n=118
|
21 participants
|
—
|
|
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
Three or More at End of Study Treatment due to Other n=39
|
0 participants
|
—
|
PRIMARY outcome
Timeframe: Up to approximately 5.7 yearsPopulation: The biomarker analysis set (BAS) included participants who received at least one dose of either ribociclib or letrozole and who had an evaluable biomarker profile (i.e., both valid liquid biopsy and TK1 serum samples collected at screening) and who did not have violations of the main inclusion-exclusion criteria. Data are reported only for participants with target mutation.
The target mutation was defined as the hotspot mutation with the highest molecular frequency observed at screening excluding single nucleotide polymorphisms (SNPs, i.e., hotspot mutations observed at all timepoints with a minimum molecular frequency value of 30% and a variation coefficient greater than 0.15). The molecular frequency of target mutation at performed assessments during which the target mutation was not detected was assumed to be equal to 0%.
Outcome measures
| Measure |
Ribociclib+Letrozole (Core Phase)
n=263 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Percent Change From Screening in Target Mutation Variant Allele Frequency (VAF)
Cycle 1, Day 15 n=104
|
-94.33 percent change
Interval -100.0 to 134.5
|
—
|
|
Percent Change From Screening in Target Mutation Variant Allele Frequency (VAF)
Cycle 2, Day 1 n=106
|
-100.00 percent change
Interval -100.0 to 167.8
|
—
|
|
Percent Change From Screening in Target Mutation Variant Allele Frequency (VAF)
First Imaging Evaluation n=90
|
-100.00 percent change
Interval -100.0 to 1110.9
|
—
|
|
Percent Change From Screening in Target Mutation Variant Allele Frequency (VAF)
End of Treatment due to PD n=66
|
-47.48 percent change
Interval -100.0 to 1133.9
|
—
|
|
Percent Change From Screening in Target Mutation Variant Allele Frequency (VAF)
End of treatment due to other n=16
|
-100.00 percent change
Interval -100.0 to 29.8
|
—
|
PRIMARY outcome
Timeframe: Up to approximately 1.6 yearsPopulation: The biomarker analysis set - extension phase (BAS-EXT) included participants entering the extension phase who received at least one dose of study medication defined as either alpelisib or fulvestrant who had an evaluable biomarker profile (at least baseline samples) and who did not have violations of the main inclusion-exclusion criteria.
PR was assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1, criteria and was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the screening sum of diameters.
Outcome measures
| Measure |
Ribociclib+Letrozole (Core Phase)
n=21 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Number of Participants With Partial Response (PR) in the Extension Phase
|
3 participants
|
—
|
SECONDARY outcome
Timeframe: Up to approximately 5.7 yearsPopulation: The biomarker analysis set (BAS) included participants who received at least one dose of either ribociclib or letrozole and who had an evaluable biomarker profile (i.e., both valid liquid biopsy and TK1 serum samples collected at screening) and who did not have violations of the main inclusion-exclusion criteria.
Outcome measures
| Measure |
Ribociclib+Letrozole (Core Phase)
n=263 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Percent Change From Screening in Thymidine Kinase 1 (TK1) Serum Level
Cycle 1, Day 15 n=245
|
-73.2 percent change
Interval -99.0 to 2370.0
|
—
|
|
Percent Change From Screening in Thymidine Kinase 1 (TK1) Serum Level
Cycle 2, Day 1 n=241
|
-39.3 percent change
Interval -96.0 to 1378.0
|
—
|
|
Percent Change From Screening in Thymidine Kinase 1 (TK1) Serum Level
First Imaging Evaluation n=208
|
-46.9 percent change
Interval -99.0 to 1604.0
|
—
|
|
Percent Change From Screening in Thymidine Kinase 1 (TK1) Serum Level
End of Treatment due to PD n=89
|
56.5 percent change
Interval -98.0 to 10033.0
|
—
|
|
Percent Change From Screening in Thymidine Kinase 1 (TK1) Serum Level
End of treatment due to other n=35
|
28.5 percent change
Interval -92.0 to 109213.0
|
—
|
SECONDARY outcome
Timeframe: Up to approximately 5.7 yearsPopulation: The biomarker analysis set (BAS) included participants who received at least one dose of either ribociclib or letrozole and who had an evaluable biomarker profile (i.e., both valid liquid biopsy and TK1 serum samples collected at screening) and who did not have violations of the main inclusion-exclusion criteria.
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Outcome measures
| Measure |
Ribociclib+Letrozole (Core Phase)
n=95 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
One at End of Study Treatment due to Other n=4
|
3 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
Three or More at End of Study Treatment due to Other n=4
|
0 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
None at Screening n=95
|
64 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
None at Cycle 1 Day 15 n=84
|
60 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
None at Cycle 2, Day 1 n=91
|
67 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
None at First Imaging Evaluation n=82
|
66 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
None at End of Study Treatment due to PD n=27
|
14 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
None at End of Study Treatment due to Other n=4
|
1 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
One at Screening n=95
|
23 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
One at Cycle 1 Day 15 n=84
|
18 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
One at Cycle 2, Day 1 n=91
|
22 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
One at First Imaging Evaluation n=82
|
14 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
One at End of Study Treatment due to PD n=27
|
7 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
Two at Screening n=95
|
4 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
Two at Cycle 1 Day 15 n=84
|
4 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
Two at Cycle 2, Day 1 n=91
|
2 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
Two at First Imaging Evaluation n=82
|
2 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
Two at End of Study Treatment due to PD n=27
|
2 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
Two at End of Study Treatment due to Other n=4
|
0 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
Three or More at Screening n=95
|
4 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
Three or More at Cycle 1 Day 15 n=84
|
2 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
Three or More at Cycle 2, Day 1 n=91
|
0 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
Three or More at First Imaging Evaluation n=82
|
0 participants
|
—
|
|
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
Three or More at End of Study Treatment due to PD n=27
|
4 participants
|
—
|
SECONDARY outcome
Timeframe: Up to approximately 5.7 yearsPopulation: The biomarker analysis set (BAS) included participants who received at least one dose of either ribociclib or letrozole and who had an evaluable biomarker profile (i.e., both valid liquid biopsy and TK1 serum samples collected at screening) and who did not have violations of the main inclusion-exclusion criteria.
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Outcome measures
| Measure |
Ribociclib+Letrozole (Core Phase)
n=21 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
None at Cycle 2, Day 1 n=21
|
9 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
None at First Imaging Evaluation n=19
|
9 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
None at End of Study Treatment due to PD n=20
|
7 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
One at Cycle 2, Day 1 n=21
|
3 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
One at First Imaging Evaluation n=19
|
3 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
Three or More at Screening n=21
|
3 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
Three or More at Cycle 1 Day 15 n=19
|
1 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
None at Screening n=21
|
8 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
None at Cycle 1 Day 15 n=19
|
7 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
One at Screening n=21
|
5 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
One at Cycle 1 Day 15 n=19
|
3 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
One at End of Study Treatment due to PD n=20
|
4 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
Two at Screening n=21
|
5 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
Two at Cycle 1 Day 15 n=19
|
8 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
Two at Cycle 2, Day 1 n=21
|
5 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
Two at First Imaging Evaluation n=19
|
5 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
Two at End of Study Treatment due to PD n=20
|
5 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
Three or More at Cycle 2, Day 1 n=21
|
4 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
Three or More at First Imaging Evaluation n=19
|
2 participants
|
—
|
|
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
Three or More at End of Study Treatment due to PD n=20
|
4 participants
|
—
|
SECONDARY outcome
Timeframe: Up to approximately 5.7 yearsPopulation: The biomarker analysis set (BAS) included participants who received at least one dose of either ribociclib or letrozole and who had an evaluable biomarker profile (i.e., both valid liquid biopsy and TK1 serum samples collected at screening) and who did not have violations of the main inclusion-exclusion criteria. Data are reported only for participants with target mutation.
The target mutation was defined as the hotspot mutation with the highest molecular frequency observed at screening excluding single nucleotide polymorphisms (SNPs, i.e., hotspot mutations observed at all timepoints with a minimum molecular frequency value of 30% and a variation coefficient greater than 0.15). The molecular frequency of target mutation at performed assessments during which the target mutation was not detected was assumed to be equal to 0%.
Outcome measures
| Measure |
Ribociclib+Letrozole (Core Phase)
n=28 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Percent Change From Screening in Target Mutation Molecular Frequency (VAF) for Long Responders
First Imaging Evaluation n=23
|
-100.00 percent change
Interval -100.0 to 40.5
|
—
|
|
Percent Change From Screening in Target Mutation Molecular Frequency (VAF) for Long Responders
Cycle 1, Day 15 n=26
|
-98.82 percent change
Interval -100.0 to 101.6
|
—
|
|
Percent Change From Screening in Target Mutation Molecular Frequency (VAF) for Long Responders
Cycle 2, Day 1 n=27
|
-100.00 percent change
Interval -100.0 to 88.8
|
—
|
|
Percent Change From Screening in Target Mutation Molecular Frequency (VAF) for Long Responders
End of Treatment due to PD n=12
|
-52.93 percent change
Interval -100.0 to 319.7
|
—
|
|
Percent Change From Screening in Target Mutation Molecular Frequency (VAF) for Long Responders
End of treatment due to other n=2
|
-35.12 percent change
Interval -100.0 to 29.8
|
—
|
SECONDARY outcome
Timeframe: Up to approximately 5.7 yearsPopulation: The biomarker analysis set (BAS) included participants who received at least one dose of either ribociclib or letrozole and who had an evaluable biomarker profile (i.e., both valid liquid biopsy and TK1 serum samples collected at screening) and who did not have violations of the main inclusion-exclusion criteria. Data are reported only for participants with the target mutation.
The target mutation was defined as the hotspot mutation with the highest molecular frequency observed at screening excluding single nucleotide polymorphisms (SNPs, i.e., hotspot mutations observed at all timepoints with a minimum molecular frequency value of 30% and a variation coefficient greater than 0.15). The molecular frequency of target mutation at performed assessments during which the target mutation was not detected was assumed to be equal to 0%.
Outcome measures
| Measure |
Ribociclib+Letrozole (Core Phase)
n=13 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Percent Change From Screening in Target Mutation Molecular Frequency (VAF) for Early Progressors
First Imaging Evaluation n=11
|
-56.76 percent change
Interval -100.0 to 1110.9
|
—
|
|
Percent Change From Screening in Target Mutation Molecular Frequency (VAF) for Early Progressors
Cycle 1, Day 15 n=12
|
-42.45 percent change
Interval -100.0 to 77.5
|
—
|
|
Percent Change From Screening in Target Mutation Molecular Frequency (VAF) for Early Progressors
Cycle 2, Day 1 n=13
|
-70.05 percent change
Interval -100.0 to 37.9
|
—
|
|
Percent Change From Screening in Target Mutation Molecular Frequency (VAF) for Early Progressors
End of Treatment due to PD n=12
|
-24.31 percent change
Interval -100.0 to 707.2
|
—
|
SECONDARY outcome
Timeframe: Up to approximately 5.7 yearsPopulation: The biomarker analysis set (BAS) included participants who received at least one dose of either ribociclib or letrozole and who had an evaluable biomarker profile (i.e., both valid liquid biopsy and TK1 serum samples collected at screening) and who did not have violations of the main inclusion-exclusion criteria.
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Outcome measures
| Measure |
Ribociclib+Letrozole (Core Phase)
n=105 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Number of Screening Hotspot Mutations Per De Novo Patient in Liquid Biopsy Samples and Tissue Samples
One (Valid Tissue Sample) n=72
|
26 participants
|
—
|
|
Number of Screening Hotspot Mutations Per De Novo Patient in Liquid Biopsy Samples and Tissue Samples
Two (Valid Tissue Sample) n=72
|
17 participants
|
—
|
|
Number of Screening Hotspot Mutations Per De Novo Patient in Liquid Biopsy Samples and Tissue Samples
None (Valid Liquid Biopsy Sample) n=105
|
59 participants
|
—
|
|
Number of Screening Hotspot Mutations Per De Novo Patient in Liquid Biopsy Samples and Tissue Samples
One (Valid Liquid Biopsy Sample) n=105
|
31 participants
|
—
|
|
Number of Screening Hotspot Mutations Per De Novo Patient in Liquid Biopsy Samples and Tissue Samples
Two (Valid Liquid Biopsy Sample) n=105
|
11 participants
|
—
|
|
Number of Screening Hotspot Mutations Per De Novo Patient in Liquid Biopsy Samples and Tissue Samples
Three or More (Valid Liquid Biopsy Sample) n=105
|
4 participants
|
—
|
|
Number of Screening Hotspot Mutations Per De Novo Patient in Liquid Biopsy Samples and Tissue Samples
None (Valid Tissue Sample) n=72
|
23 participants
|
—
|
|
Number of Screening Hotspot Mutations Per De Novo Patient in Liquid Biopsy Samples and Tissue Samples
Three or More (Valid Tissue Sample) n=72
|
6 participants
|
—
|
SECONDARY outcome
Timeframe: Up to approximately 5.7 yearsPopulation: The biomarker analysis set (BAS) included participants who received at least one dose of either ribociclib or letrozole and who had an evaluable biomarker profile (i.e., both valid liquid biopsy and TK1 serum samples collected at screening) and who did not have violations of the main inclusion-exclusion criteria.
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Outcome measures
| Measure |
Ribociclib+Letrozole (Core Phase)
n=158 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Number of Screening Hotspot Mutations Per Recurrent Patient in Liquid Biopsy Samples and Tissue Samples
Two (Valid Liquid Biopsy Sample) n=158
|
21 participants
|
—
|
|
Number of Screening Hotspot Mutations Per Recurrent Patient in Liquid Biopsy Samples and Tissue Samples
Three or More (Valid Liquid Biopsy Sample) n=158
|
12 participants
|
—
|
|
Number of Screening Hotspot Mutations Per Recurrent Patient in Liquid Biopsy Samples and Tissue Samples
None (Valid Tissue Sample) n=67
|
15 participants
|
—
|
|
Number of Screening Hotspot Mutations Per Recurrent Patient in Liquid Biopsy Samples and Tissue Samples
One (Valid Tissue Sample) n=67
|
25 participants
|
—
|
|
Number of Screening Hotspot Mutations Per Recurrent Patient in Liquid Biopsy Samples and Tissue Samples
None (Valid Liquid Biopsy Sample) n=158
|
86 participants
|
—
|
|
Number of Screening Hotspot Mutations Per Recurrent Patient in Liquid Biopsy Samples and Tissue Samples
One (Valid Liquid Biopsy Sample) n=158
|
39 participants
|
—
|
|
Number of Screening Hotspot Mutations Per Recurrent Patient in Liquid Biopsy Samples and Tissue Samples
Two (Valid Tissue Sample) n=67
|
13 participants
|
—
|
|
Number of Screening Hotspot Mutations Per Recurrent Patient in Liquid Biopsy Samples and Tissue Samples
Three or More (Valid Tissue Sample) n=67
|
14 participants
|
—
|
SECONDARY outcome
Timeframe: Up to approximately 5.7 yearsPopulation: The biomarker analysis set (BAS) included participants who received at least one dose of either ribociclib or letrozole and who had an evaluable biomarker profile (i.e., both valid liquid biopsy and TK1 serum samples collected at screening) and who did not have violations of the main inclusion-exclusion criteria. Data are reported for participants with both valid baseline liquid biopsy and tissue samples.
Results data refer to the total number of evaluations (i.e. the number of participants in the biomarker analysis set with both valid baseline liquid biopsy and tissue sample multiplied by 39 considered genes).
Outcome measures
| Measure |
Ribociclib+Letrozole (Core Phase)
n=263 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Overall Number of Evaluations of Hotspot Mutations and Non-hotspot Mutations Present in Both Liquid Biopsies and Tissue Samples at Screening
Liquid Biopsy Hotspot-mutated, Tissue Sample Hotspot-mutated
|
68 evaluations
|
—
|
|
Overall Number of Evaluations of Hotspot Mutations and Non-hotspot Mutations Present in Both Liquid Biopsies and Tissue Samples at Screening
Liquid Biopsy Hotspot-mutated, Tissue Sample Not Hotspot-mutated
|
27 evaluations
|
—
|
|
Overall Number of Evaluations of Hotspot Mutations and Non-hotspot Mutations Present in Both Liquid Biopsies and Tissue Samples at Screening
Liquid Biopsy Not Hotspot-mutated, Tissue Sample Hotspot-mutated
|
99 evaluations
|
—
|
|
Overall Number of Evaluations of Hotspot Mutations and Non-hotspot Mutations Present in Both Liquid Biopsies and Tissue Samples at Screening
Liquid Biopsy Not Hotspot-mutated, Tissue Sample Not Hotspot-mutated
|
5227 evaluations
|
—
|
SECONDARY outcome
Timeframe: Up to approximately 5.7 yearsPopulation: The biomarker analysis set (BAS) included participants who received at least one dose of either ribociclib or letrozole and who had an evaluable biomarker profile (i.e., both valid liquid biopsy and TK1 serum samples collected at screening) and who did not have violations of the main inclusion-exclusion criteria. Data are reported for participants with both valid baseline liquid biopsy and tissue samples.
Results data refer to the total number of evaluations (i.e. the number of participants in the biomarker analysis set with both valid baseline liquid biopsy and tissue sample multiplied by 39 considered genes).
Outcome measures
| Measure |
Ribociclib+Letrozole (Core Phase)
n=263 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Overall Number of Evaluations of Hotspot Mutations and Non-hotspot Mutations Present in Both Liquid Biopsies and Tissue Samples at End of Treatment
Liquid Biopsy Hotspot-mutated, Tissue Sample Hotspot-mutated
|
5 evaluations
|
—
|
|
Overall Number of Evaluations of Hotspot Mutations and Non-hotspot Mutations Present in Both Liquid Biopsies and Tissue Samples at End of Treatment
Liquid Biopsy Hotspot-mutated, Tissue Sample Not Hotspot-mutated
|
1 evaluations
|
—
|
|
Overall Number of Evaluations of Hotspot Mutations and Non-hotspot Mutations Present in Both Liquid Biopsies and Tissue Samples at End of Treatment
Liquid Biopsy Not Hotspot-mutated, Tissue Sample Hotspot-mutated
|
0 evaluations
|
—
|
|
Overall Number of Evaluations of Hotspot Mutations and Non-hotspot Mutations Present in Both Liquid Biopsies and Tissue Samples at End of Treatment
Liquid Biopsy Not Hotspot-mutated, Tissue Sample Not Hotspot-mutated
|
150 evaluations
|
—
|
SECONDARY outcome
Timeframe: Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 yearsPopulation: BAS (core phase) and BAS-EXT (extension phase)
Time to progression (TTP) was defined as time from date of start of treatment to the date of event defined as the first documented progression or death due to underlying cancer.
Outcome measures
| Measure |
Ribociclib+Letrozole (Core Phase)
n=263 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
n=21 Participants
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Time to Progression (TTP)
|
30.42 months
Interval 21.42 to 40.41
|
10.25 months
Interval 5.59 to 11.43
|
SECONDARY outcome
Timeframe: Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 yearsPopulation: BAS (core phase) and BAS-EXT (extension phase)
ORR was defined as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR): (CR+PR) per Response Evaluation Criteria in Solid Tumors (RECIST), v. 1.1. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Outcome measures
| Measure |
Ribociclib+Letrozole (Core Phase)
n=236 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
n=17 Participants
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Percentage of Participants With Best Overall Response Rate of Complete Response (CR) or Partial Response (PR)
|
38.56 percentage of participants
Interval 32.32 to 45.09
|
17.65 percentage of participants
Interval 3.8 to 43.43
|
SECONDARY outcome
Timeframe: Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 yearsPopulation: BAS (core phase) and BAS-EXT (extension phase)
Clinical benefit rate (CBR) was defined as the percentage of participants with a best overall response of complete response (CR), or partial response (PR) or an overall lesion response of stable disease (SD), lasting as per local review, for a duration of at least 24 weeks. Per RECIST v. 1.1, CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started.
Outcome measures
| Measure |
Ribociclib+Letrozole (Core Phase)
n=236 Participants
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
n=17 Participants
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Percentage of Participants With Clinical Benefit Rate
|
73.31 percentage of participants
Interval 67.18 to 78.84
|
47.06 percentage of participants
Interval 22.98 to 72.19
|
SECONDARY outcome
Timeframe: Up to approximately 5.7 yearsPopulation: An insufficient number of tissue samples were collected at the end-of-treatment timepoint to enable scientifically meaningful analyses. Tissue collection at this timepoint was subject to feasibility and patient consent. Given the limited number of samples obtained, the study team concluded that the scientific objective could not be achieved. Consequently, it was concluded and documented in the statistical analysis plan that this analysis would not be performed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to approximately 5.7 yearsPopulation: An insufficient number of tissue samples were collected at the end-of-treatment timepoint to enable scientifically meaningful analyses. Tissue collection at this timepoint was subject to feasibility and patient consent. Given the limited number of samples obtained, the study team concluded that the scientific objective could not be achieved. Consequently, it was concluded and documented in the statistical analysis plan that this analysis would not be performed.
Outcome measures
Outcome data not reported
Adverse Events
Ribociclib+Letrozole (Core Phase)
Serious events: 79 serious events
Other events: 275 other events
Deaths: 27 deaths
Alpelisib+Fulvestrant (Extension Phase)
Serious events: 6 serious events
Other events: 20 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Ribociclib+Letrozole (Core Phase)
n=287 participants at risk
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
n=21 participants at risk
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
General disorders
Pain
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Blood and lymphatic system disorders
Anaemia
|
0.70%
2/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Cardiac disorders
Acute myocardial infarction
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Cardiac disorders
Aortic valve stenosis
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Cardiac disorders
Atrial fibrillation
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Cardiac disorders
Atrial flutter
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Cardiac disorders
Atrioventricular block second degree
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Cardiac disorders
Cardiac failure
|
0.70%
2/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Cardiac disorders
Myocarditis
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Endocrine disorders
Hypothyroidism
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Eye disorders
Lens dislocation
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Gastrointestinal disorders
Constipation
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.70%
2/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Gastrointestinal disorders
Gastric perforation
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Gastrointestinal disorders
Vomiting
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
General disorders
Death
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
General disorders
General physical health deterioration
|
1.0%
3/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
General disorders
Hyperpyrexia
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
General disorders
Pyrexia
|
1.0%
3/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
General disorders
Sudden death
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Hepatobiliary disorders
Hepatotoxicity
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Hepatobiliary disorders
Hypertransaminasaemia
|
0.00%
0/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Immune system disorders
Anaphylactic shock
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Infections and infestations
COVID-19
|
0.70%
2/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Infections and infestations
Campylobacter infection
|
0.00%
0/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Infections and infestations
Diverticulitis
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Infections and infestations
Hepatitis A
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Infections and infestations
Pneumonia
|
1.0%
3/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Infections and infestations
Pneumonia bacterial
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Infections and infestations
Sepsis
|
0.70%
2/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Infections and infestations
Urinary tract infection
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
1.0%
3/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Injury, poisoning and procedural complications
Injury
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Injury, poisoning and procedural complications
Overdose
|
1.0%
3/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Injury, poisoning and procedural complications
Product dispensing error
|
1.4%
4/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Investigations
Alanine aminotransferase increased
|
1.0%
3/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Investigations
Aspartate aminotransferase increased
|
1.0%
3/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Investigations
Blood creatinine increased
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Investigations
Electrocardiogram QT prolonged
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Investigations
Haemoglobin decreased
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Investigations
Platelet count decreased
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.70%
2/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
9.5%
2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
1.0%
3/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
0.70%
2/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.00%
0/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Nervous system disorders
Aphasia
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.70%
2/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Nervous system disorders
Cerebrovascular accident
|
1.4%
4/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Nervous system disorders
Cognitive disorder
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Nervous system disorders
Coma
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Nervous system disorders
Encephalopathy
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Nervous system disorders
Hemiparesis
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Nervous system disorders
Somnolence
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Nervous system disorders
Syncope
|
0.70%
2/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Nervous system disorders
Transient ischaemic attack
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Nervous system disorders
Tremor
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Product Issues
Device dislocation
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Psychiatric disorders
Anxiety disorder
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Renal and urinary disorders
Renal failure
|
0.70%
2/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.4%
7/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.70%
2/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary artery thrombosis
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.4%
4/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.0%
3/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Vascular disorders
Endocrine hypertension
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
Other adverse events
| Measure |
Ribociclib+Letrozole (Core Phase)
n=287 participants at risk
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
|
Alpelisib+Fulvestrant (Extension Phase)
n=21 participants at risk
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28-day cycle
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
33.1%
95/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
33.3%
7/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Gastrointestinal disorders
Diarrhoea
|
19.5%
56/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
57.1%
12/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Gastrointestinal disorders
Abdominal pain
|
7.0%
20/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.6%
16/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Gastrointestinal disorders
Constipation
|
9.4%
27/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Blood and lymphatic system disorders
Anaemia
|
36.6%
105/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
9.5%
2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Blood and lymphatic system disorders
Leukopenia
|
32.4%
93/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Blood and lymphatic system disorders
Neutropenia
|
69.0%
198/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
11.1%
32/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Gastrointestinal disorders
Stomatitis
|
3.1%
9/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
14.3%
3/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Gastrointestinal disorders
Vomiting
|
16.4%
47/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
14.3%
3/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
General disorders
Asthenia
|
31.0%
89/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
38.1%
8/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
General disorders
Chest pain
|
2.8%
8/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
9.5%
2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
General disorders
Fatigue
|
9.8%
28/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
General disorders
Mucosal inflammation
|
5.6%
16/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
23.8%
5/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
General disorders
Oedema peripheral
|
4.9%
14/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
9.5%
2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
General disorders
Pain
|
1.4%
4/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
9.5%
2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
General disorders
Pyrexia
|
19.5%
56/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
19.0%
4/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Infections and infestations
COVID-19
|
5.6%
16/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Investigations
Alanine aminotransferase increased
|
20.2%
58/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
14.3%
3/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Investigations
Aspartate aminotransferase increased
|
18.5%
53/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
14.3%
3/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Investigations
Blood alkaline phosphatase increased
|
4.5%
13/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
9.5%
2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Investigations
Blood creatinine increased
|
9.8%
28/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
14.3%
3/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Investigations
Electrocardiogram QT prolonged
|
6.3%
18/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Investigations
Lymphocyte count decreased
|
5.6%
16/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Investigations
Neutrophil count decreased
|
19.5%
56/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Investigations
Platelet count decreased
|
10.5%
30/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Investigations
Weight decreased
|
2.1%
6/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
23.8%
5/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Investigations
White blood cell count decreased
|
21.3%
61/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
8.0%
23/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
14.3%
3/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
3.8%
11/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
66.7%
14/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
19.5%
56/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.4%
27/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
9.5%
2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
9.8%
28/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
9.5%
2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
3.8%
11/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
9.5%
2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.2%
15/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
0.00%
0/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Nervous system disorders
Dysgeusia
|
3.8%
11/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
9.5%
2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Nervous system disorders
Headache
|
7.3%
21/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.6%
42/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
8.0%
23/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
9.5%
2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.35%
1/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
9.5%
2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.70%
2/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
9.5%
2/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
9.4%
27/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
16.4%
47/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
14.3%
3/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Skin and subcutaneous tissue disorders
Rash
|
11.1%
32/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
38.1%
8/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
|
Vascular disorders
Hypertension
|
5.6%
16/287 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
4.8%
1/21 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER