A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
This is an umbrella study evaluating the efficacy and safety of multiple treatment
combinations in participants with metastatic or inoperable locally advanced breast cancer.
The study will be performed in two stages. During Stage 1, four cohorts will be enrolled in
parallel in this study:
Cohort 1 will consist of Programmed death-ligand 1 (PD-L1)-positive participants who have
received no prior systemic therapy for metastatic or inoperable locally advanced
triple-negative breast cancer (TNBC) (first-line [1L] PD-L1+ cohort).
Cohort 2 will consist of participants who had disease progression during or following 1L
treatment with chemotherapy for metastatic or inoperable locally-advanced TNBC and have not
received cancer immunotherapy (CIT) (second-line [2L] CIT-naive cohort).
Cohort 3 will consist of participants with locally-advanced or metastatic HR+, HER2-negative
disease with PIK3CA mutation who may or may not have had disease progression during or
following previous lines of treatment for metastatic disease (HR+cohort).
Cohort 4 will consist of participants with locally-advanced or metastatic HER2+ /HER2-low
disease with PIK3CA mutation who had disease progression on standard-of-care therapies (HER2+
/HER2-low cohort).
In each cohort, eligible participants will initially be assigned to one of several treatment
arms (Stage 1). In addition, participants in the 2L CIT-nave cohort who experience disease
progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be
eligible to continue treatment with a different treatment combination (Stage 2), provided
Stage 2 is open for enrollment.
combinations in participants with metastatic or inoperable locally advanced breast cancer.
The study will be performed in two stages. During Stage 1, four cohorts will be enrolled in
parallel in this study:
Cohort 1 will consist of Programmed death-ligand 1 (PD-L1)-positive participants who have
received no prior systemic therapy for metastatic or inoperable locally advanced
triple-negative breast cancer (TNBC) (first-line [1L] PD-L1+ cohort).
Cohort 2 will consist of participants who had disease progression during or following 1L
treatment with chemotherapy for metastatic or inoperable locally-advanced TNBC and have not
received cancer immunotherapy (CIT) (second-line [2L] CIT-naive cohort).
Cohort 3 will consist of participants with locally-advanced or metastatic HR+, HER2-negative
disease with PIK3CA mutation who may or may not have had disease progression during or
following previous lines of treatment for metastatic disease (HR+cohort).
Cohort 4 will consist of participants with locally-advanced or metastatic HER2+ /HER2-low
disease with PIK3CA mutation who had disease progression on standard-of-care therapies (HER2+
/HER2-low cohort).
In each cohort, eligible participants will initially be assigned to one of several treatment
arms (Stage 1). In addition, participants in the 2L CIT-nave cohort who experience disease
progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be
eligible to continue treatment with a different treatment combination (Stage 2), provided
Stage 2 is open for enrollment.
Not Available
Phase I/II
Adults
Not Available
Not Available
Abramson, Vandana
International
Vanderbilt University
09-01-2021
Eligibility
18 Years
BOTH
NO
Inclusion Criteria:
Inclusion Criteria Patients must meet all of the following criteria to qualify for Stage 1 (all cohorts) and to qualify for Stage 2 (2L CIT-nave cohort): - Age >/= 18 years at the time of signing Informed Consent Form - ECOG Performance Status of 0 or 1 - Able to comply with the study protocol, in the investigator's judgment - Metastatic or inoperable locally advanced breast cancer - Measurable disease (at least one target lesion) according to RECIST v1.1 - Life expectancy >/= 3 months, as determined by the investigator - Tumor accessible for biopsy - Availability of a representative tumor specimen that is suitable for biomarker analysis via central testing - Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment - For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from breastfeeding and donating eggs, as outlined for each specific treatment arm - For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm Inclusion criteria for Cohort 1 - Metastatic or inoperable locally advanced, histologically documented TNBC - No prior systemic treatment for metastatic or inoperable locally advanced TNBC - Positive PD-L1 expression, defined as >/= 1% of the tumor area occupied by PD L1-expressing tumor-infiltrating immune cells of any intensity, as determined through use of the U.S. Food and Drug Administration-approved or CE-marked Ventana PD-L1 (SP142) Assay Inclusion criteria for Cohort 2 - Metastatic or inoperable locally advanced, histologically documented TNBC - Eligible for capecitabine monotherapy - Radiologic/objective evidence of recurrence or disease progression after 1L treatment with chemotherapy, for a total of one line of therapy for inoperable locally advanced or metastatic breast cancer Inclusion criteria for Cohort 3 - Metastatic or inoperable locally-advanced, histologically documented HR+ breast cancer who had previous lines of treatment for metastatic disease. - Fasting glucose 126 mg/dL or 7.0 mmol/L and HbA1c
Inclusion Criteria Patients must meet all of the following criteria to qualify for Stage 1 (all cohorts) and to qualify for Stage 2 (2L CIT-nave cohort): - Age >/= 18 years at the time of signing Informed Consent Form - ECOG Performance Status of 0 or 1 - Able to comply with the study protocol, in the investigator's judgment - Metastatic or inoperable locally advanced breast cancer - Measurable disease (at least one target lesion) according to RECIST v1.1 - Life expectancy >/= 3 months, as determined by the investigator - Tumor accessible for biopsy - Availability of a representative tumor specimen that is suitable for biomarker analysis via central testing - Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment - For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from breastfeeding and donating eggs, as outlined for each specific treatment arm - For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm Inclusion criteria for Cohort 1 - Metastatic or inoperable locally advanced, histologically documented TNBC - No prior systemic treatment for metastatic or inoperable locally advanced TNBC - Positive PD-L1 expression, defined as >/= 1% of the tumor area occupied by PD L1-expressing tumor-infiltrating immune cells of any intensity, as determined through use of the U.S. Food and Drug Administration-approved or CE-marked Ventana PD-L1 (SP142) Assay Inclusion criteria for Cohort 2 - Metastatic or inoperable locally advanced, histologically documented TNBC - Eligible for capecitabine monotherapy - Radiologic/objective evidence of recurrence or disease progression after 1L treatment with chemotherapy, for a total of one line of therapy for inoperable locally advanced or metastatic breast cancer Inclusion criteria for Cohort 3 - Metastatic or inoperable locally-advanced, histologically documented HR+ breast cancer who had previous lines of treatment for metastatic disease. - Fasting glucose 126 mg/dL or 7.0 mmol/L and HbA1c
