Trial Outcomes & Findings for Umbrella Trial of Subtype-Targeted Therapies in ER+/HER2- Breast Cancer (NCT NCT05101564)
NCT ID: NCT05101564
Last Updated: 2026-02-12
Results Overview
The primary outcome is the percentage change in Ki67 expression comparing pre-treatment to on-treatment specimens. Ki67 values were log-transformed for analysis, and results are summarized as the mean percentage change with 95% confidence intervals.
COMPLETED
PHASE2
19 participants
Measured pre-treatment and after treatment 15 or 19 days, based on the duration specified for the assigned therapy
2026-02-12
Participant Flow
Participant milestones
| Measure |
Cohort 2: Zotatifin in Combination With Fulvestrant (Treatment Arm)
Integrative subtype 2 or 6 Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) was administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1.
Zotatifin: Zotatifin 0.10mg/kg (by weight)
Fulvestrant: Fulvestrant 500 mg
|
Cohort 2: Fulvestrant (Control Arm)
Integrative subtype 2 or 6, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1.
Fulvestrant: Fulvestrant 500 mg
|
Cohort 3:Zotatifin in Combination With Fulvestrant (Treatment Arm)
Integrative subtype 3, 4, 7, or 8, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) should be administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1.
Zotatifin: Zotatifin 0.10mg/kg (by weight)
Fulvestrant: Fulvestrant 500 mg
|
Cohort 3:Fulvestrant (Control Arm)
Integrative subtype 3, 4, 7, or 8, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. on Day 1.
Fulvestrant: Fulvestrant 500 mg
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
2
|
2
|
7
|
8
|
|
Overall Study
COMPLETED
|
2
|
2
|
6
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Umbrella Trial of Subtype-Targeted Therapies in ER+/HER2- Breast Cancer
Baseline characteristics by cohort
| Measure |
Cohort 2: Zotatifin in Combination With Fulvestrant (Treatment Arm)
n=2 Participants
Integrative subtype 2 or 6, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) was administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1.
Zotatifin: Zotatifin 0.10mg/kg (by weight)
Fulvestrant: Fulvestrant 500 mg
|
Cohort 2: Fulvestrant (Control Arm)
n=2 Participants
Integrative subtype 2 or 6, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1.
Fulvestrant: Fulvestrant 500 mg
|
Cohort 3: Zotatifin in Combination With Fulvestrant (Treatment Arm)
n=7 Participants
Integrative subtype 3, 4, 7, or 8, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) was administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1.
Zotatifin: Zotatifin 0.10mg/kg (by weight)
Fulvestrant: Fulvestrant 500 mg
|
Cohort 3: Fulvestrant (Control Arm)
n=8 Participants
Integrative subtype 3, 4, 7, or 8, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. on Day 1.
Fulvestrant: Fulvestrant 500 mg
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
0 Participants
n=72 Participants
|
0 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=41 Participants
|
2 Participants
n=1581 Participants
|
6 Participants
n=4626 Participants
|
4 Participants
n=72 Participants
|
13 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
1 Participants
n=4626 Participants
|
4 Participants
n=72 Participants
|
6 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=41 Participants
|
2 Participants
n=1581 Participants
|
7 Participants
n=4626 Participants
|
8 Participants
n=72 Participants
|
19 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
0 Participants
n=72 Participants
|
0 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
4 Participants
n=4626 Participants
|
2 Participants
n=72 Participants
|
6 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
1 Participants
n=41 Participants
|
2 Participants
n=1581 Participants
|
3 Participants
n=4626 Participants
|
6 Participants
n=72 Participants
|
12 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
0 Participants
n=72 Participants
|
1 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
0 Participants
n=72 Participants
|
0 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=41 Participants
|
1 Participants
n=1581 Participants
|
1 Participants
n=4626 Participants
|
2 Participants
n=72 Participants
|
4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
1 Participants
n=72 Participants
|
1 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
0 Participants
n=72 Participants
|
0 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=41 Participants
|
1 Participants
n=1581 Participants
|
6 Participants
n=4626 Participants
|
3 Participants
n=72 Participants
|
12 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
0 Participants
n=72 Participants
|
0 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
2 Participants
n=72 Participants
|
2 Participants
|
|
Region of Enrollment
United States
|
2 participants
n=41 Participants
|
2 participants
n=1581 Participants
|
7 participants
n=4626 Participants
|
8 participants
n=72 Participants
|
19 participants
|
PRIMARY outcome
Timeframe: Measured pre-treatment and after treatment 15 or 19 days, based on the duration specified for the assigned therapyThe primary outcome is the percentage change in Ki67 expression comparing pre-treatment to on-treatment specimens. Ki67 values were log-transformed for analysis, and results are summarized as the mean percentage change with 95% confidence intervals.
Outcome measures
| Measure |
Cohort 2: Zotatifin in Combination With Fulvestrant (Treatment Arm)
n=2 Participants
Integrative subtype 2 or 6, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) was administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1.
Zotatifin: Zotatifin 0.10mg/kg (by weight)
Fulvestrant: Fulvestrant 500 mg
|
Cohort 2: Fulvestrant (Control Arm)
n=2 Participants
Integrative subtype 2 or 6, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1.
Fulvestrant: Fulvestrant 500 mg
|
Cohort 3: Zotatifin in Combination With Fulvestrant (Treatment Arm)
n=6 Participants
Integrative subtype 3, 4, 7, or 8, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) was administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1.
Zotatifin: Zotatifin 0.10mg/kg (by weight)
Fulvestrant: Fulvestrant 500 mg
|
Cohort 3: Fulvestrant (Control Arm)
n=8 Participants
Integrative subtype 3, 4, 7, or 8, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. on Day 1.
Fulvestrant: Fulvestrant 500 mg
|
|---|---|---|---|---|
|
Percentage Change in Ki67
|
-0.64 percentage
Interval -4.28 to 2.99
|
-0.68 percentage
Interval -3.99 to 2.64
|
-0.63 percentage
Interval -0.92 to -0.34
|
-0.46 percentage
Interval -0.75 to -0.17
|
SECONDARY outcome
Timeframe: 15 or 19 days, based on the duration specified for the assigned therapyThe proportions of subjects with Ki67 less than 10% after treatment. The outcome will be reported as a number without dispersion.
Outcome measures
| Measure |
Cohort 2: Zotatifin in Combination With Fulvestrant (Treatment Arm)
n=2 Participants
Integrative subtype 2 or 6, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) was administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1.
Zotatifin: Zotatifin 0.10mg/kg (by weight)
Fulvestrant: Fulvestrant 500 mg
|
Cohort 2: Fulvestrant (Control Arm)
n=2 Participants
Integrative subtype 2 or 6, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1.
Fulvestrant: Fulvestrant 500 mg
|
Cohort 3: Zotatifin in Combination With Fulvestrant (Treatment Arm)
n=6 Participants
Integrative subtype 3, 4, 7, or 8, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) was administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1.
Zotatifin: Zotatifin 0.10mg/kg (by weight)
Fulvestrant: Fulvestrant 500 mg
|
Cohort 3: Fulvestrant (Control Arm)
n=8 Participants
Integrative subtype 3, 4, 7, or 8, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. on Day 1.
Fulvestrant: Fulvestrant 500 mg
|
|---|---|---|---|---|
|
Ki67 <10% On-treatment Measurement
|
1 participants
|
1 participants
|
3 participants
|
5 participants
|
Adverse Events
Cohort 2: Zotatifin in Combination With Fulvestrant (Treatment Arm)
Cohort 2: Fulvestrant (Control Arm)
Cohort 3:Zotatifin in Combination With Fulvestrant (Treatment Arm)
Cohort 3: Fulvestrant (Control Arm)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort 2: Zotatifin in Combination With Fulvestrant (Treatment Arm)
n=2 participants at risk
Integrative subtype 2 or 6, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) was administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1.
Zotatifin: Zotatifin 0.10mg/kg (by weight)
Fulvestrant: Fulvestrant 500 mg
|
Cohort 2: Fulvestrant (Control Arm)
n=2 participants at risk
Integrative subtype 2 or 6, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1.
Fulvestrant: Fulvestrant 500 mg
|
Cohort 3:Zotatifin in Combination With Fulvestrant (Treatment Arm)
n=7 participants at risk
Integrative subtype 3, 4, 7, or 8, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) was administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1.
Zotatifin: Zotatifin 0.10mg/kg (by weight)
Fulvestrant: Fulvestrant 500 mg
|
Cohort 3: Fulvestrant (Control Arm)
n=8 participants at risk
Integrative subtype 3, 4, 7, or 8,Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. on Day 1.
Fulvestrant: Fulvestrant 500 mg
|
|---|---|---|---|---|
|
General disorders
Headache
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 2 • 1 year
|
0.00%
0/8 • 1 year
|
|
General disorders
Injection site reaction
|
0.00%
0/2 • 1 year
|
50.0%
1/2 • Number of events 1 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
12.5%
1/8 • Number of events 1 • 1 year
|
|
General disorders
Pain
|
50.0%
1/2 • Number of events 1 • 1 year
|
50.0%
1/2 • Number of events 1 • 1 year
|
42.9%
3/7 • Number of events 3 • 1 year
|
12.5%
1/8 • Number of events 1 • 1 year
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/2 • 1 year
|
50.0%
1/2 • Number of events 1 • 1 year
|
0.00%
0/7 • 1 year
|
0.00%
0/8 • 1 year
|
|
Investigations
Aspartate aminotransferase increased
|
50.0%
1/2 • Number of events 1 • 1 year
|
0.00%
0/2 • 1 year
|
0.00%
0/7 • 1 year
|
0.00%
0/8 • 1 year
|
|
Infections and infestations
CPK increased
|
50.0%
1/2 • Number of events 3 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
0.00%
0/8 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
0.00%
0/7 • 1 year
|
12.5%
1/8 • Number of events 1 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
0.00%
0/8 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
0.00%
0/7 • 1 year
|
12.5%
1/8 • Number of events 1 • 1 year
|
|
Nervous system disorders
Dizziness
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
0.00%
0/8 • 1 year
|
|
Nervous system disorders
Dysarthria
|
50.0%
1/2 • Number of events 1 • 1 year
|
0.00%
0/2 • 1 year
|
0.00%
0/7 • 1 year
|
0.00%
0/8 • 1 year
|
|
Nervous system disorders
Dysesthesia
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
0.00%
0/8 • 1 year
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
28.6%
2/7 • Number of events 2 • 1 year
|
0.00%
0/8 • 1 year
|
|
Nervous system disorders
Headache
|
50.0%
1/2 • Number of events 1 • 1 year
|
0.00%
0/2 • 1 year
|
42.9%
3/7 • Number of events 3 • 1 year
|
0.00%
0/8 • 1 year
|
|
Nervous system disorders
Paresthesia
|
50.0%
1/2 • Number of events 1 • 1 year
|
0.00%
0/2 • 1 year
|
0.00%
0/7 • 1 year
|
0.00%
0/8 • 1 year
|
|
Nervous system disorders
Peripheral motor neuropathy
|
50.0%
1/2 • Number of events 1 • 1 year
|
0.00%
0/2 • 1 year
|
0.00%
0/7 • 1 year
|
0.00%
0/8 • 1 year
|
|
Nervous system disorders
Syncope
|
50.0%
1/2 • Number of events 1 • 1 year
|
0.00%
0/2 • 1 year
|
0.00%
0/7 • 1 year
|
0.00%
0/8 • 1 year
|
|
Psychiatric disorders
Libido decreased
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
0.00%
0/8 • 1 year
|
|
Reproductive system and breast disorders
Breast pain
|
50.0%
1/2 • Number of events 1 • 1 year
|
0.00%
0/2 • 1 year
|
0.00%
0/7 • 1 year
|
12.5%
1/8 • Number of events 1 • 1 year
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
0.00%
0/8 • 1 year
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
0.00%
0/8 • 1 year
|
|
Skin and subcutaneous tissue disorders
Injection site reaction
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
0.00%
0/7 • 1 year
|
12.5%
1/8 • Number of events 1 • 1 year
|
|
Skin and subcutaneous tissue disorders
Skin Erythema
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
0.00%
0/8 • 1 year
|
|
Vascular disorders
hot flashes
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
0.00%
0/8 • 1 year
|
|
Investigations
bruising
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
0.00%
0/7 • 1 year
|
12.5%
1/8 • Number of events 1 • 1 year
|
|
Injury, poisoning and procedural complications
seroma
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
0.00%
0/7 • 1 year
|
12.5%
1/8 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
0.00%
0/8 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
sore throat
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
0.00%
0/8 • 1 year
|
|
Gastrointestinal disorders
Stomach pain
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
0.00%
0/8 • 1 year
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
1/2 • Number of events 1 • 1 year
|
0.00%
0/2 • 1 year
|
0.00%
0/7 • 1 year
|
0.00%
0/8 • 1 year
|
|
General disorders
Fatigue
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
71.4%
5/7 • Number of events 5 • 1 year
|
12.5%
1/8 • Number of events 1 • 1 year
|
|
General disorders
Fever
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
0.00%
0/8 • 1 year
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
0.00%
0/8 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
50.0%
1/2 • Number of events 1 • 1 year
|
0.00%
0/2 • 1 year
|
42.9%
3/7 • Number of events 3 • 1 year
|
0.00%
0/8 • 1 year
|
|
Blood and lymphatic system disorders
Hematoma
|
50.0%
1/2 • Number of events 1 • 1 year
|
0.00%
0/2 • 1 year
|
0.00%
0/7 • 1 year
|
0.00%
0/8 • 1 year
|
|
Cardiac disorders
Palpitations
|
50.0%
1/2 • Number of events 1 • 1 year
|
0.00%
0/2 • 1 year
|
0.00%
0/7 • 1 year
|
0.00%
0/8 • 1 year
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
0.00%
0/8 • 1 year
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
12.5%
1/8 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
0.00%
0/8 • 1 year
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/2 • 1 year
|
0.00%
0/2 • 1 year
|
14.3%
1/7 • Number of events 1 • 1 year
|
0.00%
0/8 • 1 year
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place