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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

Measured pre-treatment and after treatment 15 or 19 days, based on the duration specified for the assigned therapy

Results posted on

2026-02-12

Participant Flow

Participant milestones

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

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 therapy

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.

Outcome measures

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 therapy

The proportions of subjects with Ki67 less than 10% after treatment. The outcome will be reported as a number without dispersion.

Outcome measures

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)

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Cohort 2: Fulvestrant (Control Arm)

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Cohort 3:Zotatifin in Combination With Fulvestrant (Treatment Arm)

Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths

Cohort 3: Fulvestrant (Control Arm)

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

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

Dr. Jennifer Lee Caswell-Jin

Stanford University

Phone: (650) 498-6000

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place