Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Atezolizumab-Placebo in Participants With Human Epidermal Growth Factor-2 (HER2) Positive Locally Advanced or Metastatic Breast Cancer (BC) Who Received Prior Trastuzumab and Taxane Based Therapy (NCT NCT02924883)
NCT ID: NCT02924883
Last Updated: 2021-02-17
Results Overview
PFS was defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments. Progression was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeter (mm) or the appearance of one or more new lesions.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
202 participants
Primary outcome timeframe
Baseline up to approximately 15 months
Results posted on
2021-02-17
Participant Flow
Participant milestones
| Measure |
Trastuzumab Emtansine + Atezolizumab
Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
|
Trastuzumab Emtansine + Placebo
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
|
|---|---|---|
|
Overall Study
STARTED
|
133
|
69
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
133
|
69
|
Reasons for withdrawal
| Measure |
Trastuzumab Emtansine + Atezolizumab
Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
|
Trastuzumab Emtansine + Placebo
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
|
|---|---|---|
|
Overall Study
Death
|
39
|
20
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Symptomatic Deterioration/ Clinical Progression
|
0
|
1
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
22
|
16
|
|
Overall Study
Progressive Disease
|
1
|
0
|
|
Overall Study
Study Terminated by Sponsor
|
69
|
32
|
Baseline Characteristics
A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Atezolizumab-Placebo in Participants With Human Epidermal Growth Factor-2 (HER2) Positive Locally Advanced or Metastatic Breast Cancer (BC) Who Received Prior Trastuzumab and Taxane Based Therapy
Baseline characteristics by cohort
| Measure |
Trastuzumab Emtansine + Atezolizumab
n=133 Participants
Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
|
Trastuzumab Emtansine + Placebo
n=69 Participants
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
|
Total
n=202 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53.7 Years
STANDARD_DEVIATION 9.9 • n=99 Participants
|
54.4 Years
STANDARD_DEVIATION 10.9 • n=107 Participants
|
53.9 Years
STANDARD_DEVIATION 10.3 • n=206 Participants
|
|
Sex: Female, Male
Female
|
131 Participants
n=99 Participants
|
69 Participants
n=107 Participants
|
200 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
10 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
114 Participants
n=99 Participants
|
66 Participants
n=107 Participants
|
180 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
9 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
49 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
72 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
72 Participants
n=99 Participants
|
44 Participants
n=107 Participants
|
116 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
5 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Region
USA
|
21 Number of Participants
n=99 Participants
|
11 Number of Participants
n=107 Participants
|
32 Number of Participants
n=206 Participants
|
|
Region
Western Europe
|
50 Number of Participants
n=99 Participants
|
26 Number of Participants
n=107 Participants
|
76 Number of Participants
n=206 Participants
|
|
Region
Rest of the World
|
62 Number of Participants
n=99 Participants
|
32 Number of Participants
n=107 Participants
|
94 Number of Participants
n=206 Participants
|
|
Programmed Cell-Death Ligand 1 Immunohistochemistry status
PD-L1 positive
|
57 Number of Participants
n=99 Participants
|
27 Number of Participants
n=107 Participants
|
84 Number of Participants
n=206 Participants
|
|
Programmed Cell-Death Ligand 1 Immunohistochemistry status
PD-L1 negative
|
76 Number of Participants
n=99 Participants
|
42 Number of Participants
n=107 Participants
|
118 Number of Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline up to approximately 15 monthsPopulation: The intent-to-treat (ITT) population included all randomized participants grouped according to the treatment assigned at randomization.
PFS was defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments. Progression was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeter (mm) or the appearance of one or more new lesions.
Outcome measures
| Measure |
Trastuzumab Emtansine + Placebo
n=69 Participants
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
|
Trastuzumab Emtansine + Atezolizumab
n=133 Participants
Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
|
|---|---|---|
|
Progression-Free Survival (PFS) as Determined by Investigator's Tumor Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)
|
6.8 months
Interval 4.0 to 11.1
|
8.2 months
Interval 5.8 to 10.7
|
PRIMARY outcome
Timeframe: Baseline up to study completion, approximately 40 monthsPopulation: The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Outcome measures
| Measure |
Trastuzumab Emtansine + Placebo
n=68 Participants
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
|
Trastuzumab Emtansine + Atezolizumab
n=132 Participants
Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
|
|---|---|---|
|
Percentage of Participants With Adverse Events
|
97.0 percentage of participants
|
99.2 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to study completion or death, whichever occurs first, approximately 40 monthsPopulation: The ITT population included all randomized participants grouped according to the treatment assigned at randomization.
OS was defined as the time from randomization to death from any cause.
Outcome measures
| Measure |
Trastuzumab Emtansine + Placebo
n=69 Participants
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
|
Trastuzumab Emtansine + Atezolizumab
n=133 Participants
Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
|
|---|---|---|
|
Overall Survival (OS)
|
NA Months
Median and corresponding 95% CI could not be estimated as too few patients had an event.
|
NA Months
Median and corresponding 95% CI could not be estimated as too few patients had an event.
|
SECONDARY outcome
Timeframe: Baseline up to approximately 15 monthsPopulation: The ITT population included all randomized participants grouped according to the treatment assigned at randomization. In Participants with baseline measurable disease were considered for OR. In the atezolizumab arm, one patient was not ORR evaluable.
An OR was defined as a complete or partial response determined on 2 consecutive occasions ≥ 4 weeks apart using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must be \< 10 mm on the short axis. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum. Participants who had no post-baseline tumor assessment were counted as non-responders.
Outcome measures
| Measure |
Trastuzumab Emtansine + Placebo
n=69 Participants
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
|
Trastuzumab Emtansine + Atezolizumab
n=132 Participants
Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
|
|---|---|---|
|
Percentage of Participants With Objective Response (OR) as Determined by Investigator's Tumor Assessment Using RECIST v1.1
|
43.5 Percentage of participants
|
45.5 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to approximately 15 monthsPopulation: The ITT population included all randomized participants grouped according to the treatment assigned at randomization. Participants with OR were considered for duration of OR.
Duration of OR was defined as the time from the first tumor assessment that was judged to indicate that the patient had an objective response to the time of first documented disease progression using RECIST v1.1 per investigator assessment or death from any cause, whichever occurred first.
Outcome measures
| Measure |
Trastuzumab Emtansine + Placebo
n=69 Participants
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
|
Trastuzumab Emtansine + Atezolizumab
n=133 Participants
Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
|
|---|---|---|
|
Duration of OR as Determined by Investigator's Tumor Assessment Using RECIST v1.1
|
NA Months
Interval 9.9 to
Median and upper bound of 95% CI could not be estimated as too few patients had an event.
|
NA Months
Interval 7.1 to
Median and upper bound of 95% CI could not be estimated as too few patients had an event.
|
SECONDARY outcome
Timeframe: Pre-infusion (0 hour [h]), 30 minutes (min) after end of infusion (EOI) (over 90 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycle 2 (each cycle = 21 days); at any time during study treatment/early discontinuation visit (approx. 40 months)Population: PK population included all participants who received at least one dose of trastuzumab emtansine with at least one post-dose concentration data point.
Average post infusion Trastuzumab Emtansine concentration
Outcome measures
| Measure |
Trastuzumab Emtansine + Placebo
n=110 Participants
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
|
Trastuzumab Emtansine + Atezolizumab
n=50 Participants
Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
|
|---|---|---|
|
Maximum Serum Concentration (Cmax) of Trastuzumab Emtansine
|
63.9 ug/mL
Geometric Coefficient of Variation 116.9
|
73.2 ug/mL
Geometric Coefficient of Variation 47.5
|
SECONDARY outcome
Timeframe: Pre-infusion (0 h) on Day 1 Cycle 1 and 30 min after EOI (over 90 min) on Day 1 Cycles 1 and 4 (each cycle = 21 days)Population: PK population included all participants who received at least one dose of trastuzumab emtansine with at least one post-dose concentration data point.
Average post infusion Deacetyl Mercapto 1-Oxopropyl Maytansine concentration of trastuzumab emtansine infusion
Outcome measures
| Measure |
Trastuzumab Emtansine + Placebo
n=24 Participants
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
|
Trastuzumab Emtansine + Atezolizumab
n=37 Participants
Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
|
|---|---|---|
|
Cmax of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1)
|
3.19 ng/mL
Geometric Coefficient of Variation 84.7
|
4.21 ng/mL
Geometric Coefficient of Variation 89.5
|
SECONDARY outcome
Timeframe: Pre-infusion (0 h), 30 min after EOI (over 90 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycle 2 (each cycle = 21 days)Population: PK population included all participants who received at least one dose of trastuzumab emtansine with at least one post-dose concentration data point.
Outcome measures
| Measure |
Trastuzumab Emtansine + Placebo
n=50 Participants
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
|
Trastuzumab Emtansine + Atezolizumab
n=110 Participants
Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
|
|---|---|---|
|
Cmax of Total Trastuzumab
|
86.5 ug/mL
Geometric Coefficient of Variation 26.4
|
79.5 ug/mL
Geometric Coefficient of Variation 58.3
|
SECONDARY outcome
Timeframe: Pre-infusion (0 h), 30 min after EOI (over 60 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycles 2, 3, 8, and every 8 cycles thereafter (each cycle=21 days) up to 120 days after treatment completion/early discontinuation (approx. 40 months)Population: PK population included all participants who received at least one dose of trastuzumab emtansine with at least one post-dose concentration data point.
Average post infusion atezolizumab concentration
Outcome measures
| Measure |
Trastuzumab Emtansine + Placebo
n=98 Participants
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
|
Trastuzumab Emtansine + Atezolizumab
Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
|
|---|---|---|
|
Cmax of Atezolizumab
|
626 ug/mL
Geometric Coefficient of Variation 23.0
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion (0 h) on Day 1 Cycles 1, 2, 3, 4, 8, and every 8 cycles thereafter (each cycle = 21 days) up to 120 days after treatment completion or early discontinuation (approximately 40 months)Population: The analysis population included a patient with an ATA assay result from at least one post-baseline sample.
ATAs are antibodies that inactivate the therapeutic effects of Atezolizumab. Patients are considered to be ATA positive if they are ATA negative at baseline but develop an ATA response following study drug administration (treatment-induced ATA response), or if they are ATA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold greater (i.e., ≥ 0.60 titer units) than the titer of the baseline sample (treatment-enhanced ATA response).
Outcome measures
| Measure |
Trastuzumab Emtansine + Placebo
n=131 Participants
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
|
Trastuzumab Emtansine + Atezolizumab
Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
|
|---|---|---|
|
Percentage of Participants With Anti-therapeutic Antibodies (ATAs) to Atezolizumab
|
18.3 Percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion (0 h) on Day 1 Cycles 1 and 4 (each cycle = 21 days); and at any time during study treatment/early discontinuation visit (approximately 40 months)Population: The analysis population included a patient with an ATA assay result from at least one post-baseline sample
ATAs are antibodies that inactivate the therapeutic effects of Trastuzumab Emtansine. Patients are considered to be ATA positive if they are ATA negative at baseline but develop an ATA response following study drug administration (treatment-induced ATA response), or if they are ATA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold greater (i.e., ≥ 0.60 titer units) than the titer of the baseline sample (treatment-enhanced ATA response).
Outcome measures
| Measure |
Trastuzumab Emtansine + Placebo
n=60 Participants
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
|
Trastuzumab Emtansine + Atezolizumab
n=129 Participants
Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
|
|---|---|---|
|
Percentage of Participants With ATAs to Trastuzumab Emtansine
|
0 Percentage of Participants
|
2.3 Percentage of Participants
|
Adverse Events
Trastuzumab Emtansine + Atezolizumab
Serious events: 52 serious events
Other events: 130 other events
Deaths: 42 deaths
Trastuzumab Emtansine + Placebo
Serious events: 16 serious events
Other events: 62 other events
Deaths: 22 deaths
Serious adverse events
| Measure |
Trastuzumab Emtansine + Atezolizumab
n=133 participants at risk
Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
|
Trastuzumab Emtansine + Placebo
n=67 participants at risk
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
3.0%
4/133 • Number of events 4 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Infections and infestations
Appendicitis
|
0.00%
0/133 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Infections and infestations
Influenza
|
1.5%
2/133 • Number of events 2 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Gastrointestinal disorders
Vomiting
|
2.3%
3/133 • Number of events 3 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Gastrointestinal disorders
Nausea
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Gastrointestinal disorders
Colitis
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Gastrointestinal disorders
Constipation
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Gastrointestinal disorders
Enteritis
|
0.00%
0/133 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
1.5%
2/133 • Number of events 2 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.5%
2/133 • Number of events 2 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Blood and lymphatic system disorders
Anaemia
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Nervous system disorders
Seizure
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/133 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/133 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.00%
0/133 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Cardiac disorders
Atrial thrombosis
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/133 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/133 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
3.0%
2/67 • Number of events 2 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Gastrointestinal disorders
Intra-abdominal haemorrhage
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
General disorders
Asthenia
|
0.00%
0/133 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
General disorders
Fatigue
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
General disorders
Influenza like illness
|
1.5%
2/133 • Number of events 2 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
General disorders
Malaise
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
General disorders
Non-cardiac chest pain
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
General disorders
Pyrexia
|
7.5%
10/133 • Number of events 12 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Immune system disorders
Haemophagocytic lymphohistiocytosis
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Infections and infestations
Abscess jaw
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Infections and infestations
Breast cellulitis
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Infections and infestations
Catheter site infection
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Infections and infestations
Device related infection
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Infections and infestations
Infectious pleural effusion
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Infections and infestations
Lower respiratory tract infection
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Infections and infestations
Respiratory tract infection
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Infections and infestations
Sepsis
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
3.0%
2/67 • Number of events 2 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Infections and infestations
Soft tissue infection
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Infections and infestations
Urinary tract infection
|
2.3%
3/133 • Number of events 3 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
3.0%
2/67 • Number of events 5 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/133 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Injury, poisoning and procedural complications
Subdural haemorrhage
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Investigations
Alanine aminotransferase increased
|
2.3%
3/133 • Number of events 3 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Investigations
Aspartate aminotransferase increased
|
2.3%
3/133 • Number of events 3 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis of jaw
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/133 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
0.00%
0/133 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic adenoma
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Nervous system disorders
Brain oedema
|
1.5%
2/133 • Number of events 2 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Nervous system disorders
Encephalopathy
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/133 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Psychiatric disorders
Confusional state
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Psychiatric disorders
Panic attack
|
0.00%
0/133 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Renal and urinary disorders
IgA nephropathy
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.75%
1/133 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
Other adverse events
| Measure |
Trastuzumab Emtansine + Atezolizumab
n=133 participants at risk
Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
|
Trastuzumab Emtansine + Placebo
n=67 participants at risk
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
18.0%
24/133 • Number of events 30 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
9.0%
6/67 • Number of events 7 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Blood and lymphatic system disorders
Neutropenia
|
9.8%
13/133 • Number of events 21 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
6.0%
4/67 • Number of events 4 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
31.6%
42/133 • Number of events 105 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
17.9%
12/67 • Number of events 22 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Gastrointestinal disorders
Constipation
|
21.8%
29/133 • Number of events 38 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
14.9%
10/67 • Number of events 15 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Gastrointestinal disorders
Diarrhoea
|
25.6%
34/133 • Number of events 50 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
22.4%
15/67 • Number of events 18 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Gastrointestinal disorders
Dyspepsia
|
10.5%
14/133 • Number of events 21 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
4.5%
3/67 • Number of events 3 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Gastrointestinal disorders
Nausea
|
38.3%
51/133 • Number of events 84 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
43.3%
29/67 • Number of events 37 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Gastrointestinal disorders
Stomatitis
|
9.8%
13/133 • Number of events 21 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
3.0%
2/67 • Number of events 2 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Gastrointestinal disorders
Vomiting
|
20.3%
27/133 • Number of events 36 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
22.4%
15/67 • Number of events 19 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Infections and infestations
Nasopharyngitis
|
11.3%
15/133 • Number of events 20 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
9.0%
6/67 • Number of events 8 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Injury, poisoning and procedural complications
Fall
|
7.5%
10/133 • Number of events 14 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
4.5%
3/67 • Number of events 9 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
19.5%
26/133 • Number of events 37 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
11.9%
8/67 • Number of events 9 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
18.0%
24/133 • Number of events 26 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
14.9%
10/67 • Number of events 16 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Nervous system disorders
Dizziness
|
13.5%
18/133 • Number of events 18 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
13.4%
9/67 • Number of events 10 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Nervous system disorders
Dysgeusia
|
4.5%
6/133 • Number of events 6 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
7.5%
5/67 • Number of events 6 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Nervous system disorders
Headache
|
28.6%
38/133 • Number of events 62 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
25.4%
17/67 • Number of events 27 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Nervous system disorders
Paraesthesia
|
6.8%
9/133 • Number of events 16 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
3.0%
2/67 • Number of events 2 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Psychiatric disorders
Anxiety
|
1.5%
2/133 • Number of events 2 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
9.0%
6/67 • Number of events 6 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Psychiatric disorders
Insomnia
|
10.5%
14/133 • Number of events 15 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
3.0%
2/67 • Number of events 2 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
18.8%
25/133 • Number of events 28 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
14.9%
10/67 • Number of events 12 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
12.0%
16/133 • Number of events 19 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
7.5%
5/67 • Number of events 6 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
21.1%
28/133 • Number of events 39 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
14.9%
10/67 • Number of events 13 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
17.3%
23/133 • Number of events 30 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
6.0%
4/67 • Number of events 5 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Skin and subcutaneous tissue disorders
Rash
|
24.1%
32/133 • Number of events 42 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
9.0%
6/67 • Number of events 11 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Vascular disorders
Hypertension
|
3.0%
4/133 • Number of events 4 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
6.0%
4/67 • Number of events 4 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Endocrine disorders
Hypothyroidism
|
13.5%
18/133 • Number of events 19 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
4.5%
3/67 • Number of events 3 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Eye disorders
Dry eye
|
8.3%
11/133 • Number of events 12 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
6.0%
4/67 • Number of events 4 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Eye disorders
Lacrimation increased
|
5.3%
7/133 • Number of events 9 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Eye disorders
Vision blurred
|
5.3%
7/133 • Number of events 8 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Gastrointestinal disorders
Abdominal pain
|
12.8%
17/133 • Number of events 20 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
4.5%
3/67 • Number of events 3 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
7.5%
10/133 • Number of events 10 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
4.5%
3/67 • Number of events 8 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Gastrointestinal disorders
Dry mouth
|
16.5%
22/133 • Number of events 23 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
13.4%
9/67 • Number of events 10 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
General disorders
Asthenia
|
17.3%
23/133 • Number of events 35 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
7.5%
5/67 • Number of events 6 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
General disorders
Chills
|
14.3%
19/133 • Number of events 27 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
9.0%
6/67 • Number of events 8 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
General disorders
Fatigue
|
39.8%
53/133 • Number of events 87 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
44.8%
30/67 • Number of events 43 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
General disorders
Influenza like illness
|
9.0%
12/133 • Number of events 16 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
11.9%
8/67 • Number of events 8 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
General disorders
Mucosal inflammation
|
12.0%
16/133 • Number of events 21 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
General disorders
Oedema peripheral
|
5.3%
7/133 • Number of events 9 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
6.0%
4/67 • Number of events 4 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
General disorders
Pyrexia
|
33.1%
44/133 • Number of events 72 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
17.9%
12/67 • Number of events 18 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Infections and infestations
Sinusitis
|
5.3%
7/133 • Number of events 9 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
3.0%
2/67 • Number of events 2 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Infections and infestations
Upper respiratory tract infection
|
13.5%
18/133 • Number of events 28 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
13.4%
9/67 • Number of events 12 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Infections and infestations
Urinary tract infection
|
6.8%
9/133 • Number of events 10 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
11.9%
8/67 • Number of events 10 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Investigations
Alanine aminotransferase increased
|
23.3%
31/133 • Number of events 44 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
19.4%
13/67 • Number of events 18 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Investigations
Aspartate aminotransferase increased
|
30.1%
40/133 • Number of events 56 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
20.9%
14/67 • Number of events 19 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Investigations
Blood alkaline phosphatase increased
|
8.3%
11/133 • Number of events 12 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
9.0%
6/67 • Number of events 8 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Investigations
Gamma-glutamyltransferase increased
|
5.3%
7/133 • Number of events 7 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
3.0%
2/67 • Number of events 2 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Investigations
Weight decreased
|
9.8%
13/133 • Number of events 13 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
4.5%
3/67 • Number of events 3 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
22.6%
30/133 • Number of events 52 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
17.9%
12/67 • Number of events 14 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
9.8%
13/133 • Number of events 16 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
6.0%
4/67 • Number of events 5 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.3%
15/133 • Number of events 19 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
11.9%
8/67 • Number of events 9 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
6.0%
8/133 • Number of events 8 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
4.5%
3/67 • Number of events 8 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
7.5%
10/133 • Number of events 13 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
10.4%
7/67 • Number of events 8 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
7.5%
10/133 • Number of events 12 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
9.0%
6/67 • Number of events 6 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.8%
9/133 • Number of events 10 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
6.0%
4/67 • Number of events 5 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Nervous system disorders
Neuropathy peripheral
|
13.5%
18/133 • Number of events 20 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
10.4%
7/67 • Number of events 8 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
8.3%
11/133 • Number of events 11 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
7.5%
5/67 • Number of events 6 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Nervous system disorders
Polyneuropathy
|
1.5%
2/133 • Number of events 2 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
6.0%
4/67 • Number of events 4 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.3%
7/133 • Number of events 8 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
1.5%
1/67 • Number of events 1 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
8.3%
11/133 • Number of events 12 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
0.00%
0/67 • Baseline up to study completion, approximately 40 months
The safety population is defined as all participants who received at least one dose of the study medication.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights
- Publication restrictions are in place
Restriction type: OTHER