Metastatic Breast Cancer
Conditions
Brief summary
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, six 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-naïve cohort). Cohort 3, 5, and 6 will consist of participants with locally advanced or metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative disease with one or more PIK3CA mutations. Cohort 4 will consist of participants with locally advanced or metastatic HER2+ /HER2-low disease with one or more PIK3CA mutations 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). During Stage 2, participants in the 2L CIT-naïve 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, provided Stage 2 is open for enrollment and all eligibility criteria are met.
Interventions
DRUGCapecitabine
Capecitabine will be administered 1250 milligrams per square meter (mg/m\^2) orally twice daily on Days 1-14 of each 21-day cycle.
DRUGAtezolizumab
For Atezolizumab + SGN-LIV1A, Atezolizumab + Sacituzumab Govitecan, or Atezolizumab + Chemo arms: atezolizumab will be administered intravenously (IV), 1200 mg, on Day 1 of each 21-day cycle. For Atezolizumab + Nab-Paclitaxel, Atezolizumab + Selicrelumab + Bevacizumab, Atezolizumab + Ipatasertib, or Atezolizumab + Nab-Paclitaxel + Tocilizumab arms: atezolizumab will be administered IV, 840 mg on Days 1 and 15 of each 28-day cycle.
DRUGIpatasertib
Ipatasertib will be administered by mouth 400 mg once a day, on Days 1-21 of each 28-day cycle.
DRUGSGN-LIV1A
SGN-LIV1A will be administered IV, 2.5 milligrams per kilogram (mg/kg) (maximum calculated dose 250 mg), on Day 1 of each 21-day cycle.
DRUGBevacizumab
Bevacizumab will be administered IV, 10 mg/kg, on Days 1 and 15 of each 28-day cycle.
DRUGChemotherapy (Gemcitabine + Carboplatin or Eribulin)
Gemcitabine will be administered by IV, 1000 mg/m\^2, along with carboplatin, by IV, on Days 1 and 8 of each 21-day cycle. Or Eribulin will be administered IV, 1.4 mg/m\^2 on Days 1 and 8 of each 21-day cycle.
DRUGSelicrelumab
Selicrelumab will be administered by subcutaneous (SC) injection, at a fixed dose of 16 mg on Day 1 of Cycles 1 to 4 and every third cycle thereafter (Cycle = 28 days).
DRUGTocilizumab
Tocilizumab will be administered IV, 8 mg/kg on Day 1 of each 28-day cycle.
DRUGNab-Paclitaxel
Nab-Paclitaxel will be administered IV, 100 mg/m\^2, on Days 1, 8, and 15 of each 28-day cycle.
DRUGSacituzumab Govitecan
Sacituzumab govitecan will be administered by IV infusion, 10 mg/kg, on Days 1 and 8 of each 21-day cycle.
DRUGAbemaciclib
Abemaciclib tablets will be administered at a dose of 150 mg twice daily by mouth on Days 1-28 of each 28-day cycle.
DRUGFulvestrant
For Inavolisib + Abemaciclib + Fulvestrant, Inavolisib + Ribociclib (Dose #1) + Fulvestrant, Inavolisib + Ribociclib (Dose #2) + Fulvestrant, or Inavolisib + Atirmociclib + Fulvestrant arms: Fulvestrant 500 mg, administered as an IM injection on Days 1 and 15 of Cycle 1, followed by Day 1 of each 28-day cycle thereafter. For Empa + Inavolisib + Fulvestrant ± Palbociclib, or Metformin + Inavolisib + Fulvestrant ± Palbociclib arms: Fulvestrant 500 mg, administered as an IM injection on Day 1 and as per local prescribing guidelines thereafter.
DRUGRibociclib (Dose #1)
Ribociclib tablets will be administered by mouth once daily.
DRUGInavolisib (Dose #1)
Inavolisib tablets will be administered by mouth once daily.
DRUGTrastuzumab Deruxtecan
Trastuzumab Deruxtecan will be administered IV, 5.4 mg/kg on Day 1 of each 21-day cycle.
DRUGRibociclib (Dose #2)
Ribociclib tablets will be administered by mouth once daily.
DRUGLetrozole
Letrozole tablets will be administered at a dose of 2.5 mg once a day by mouth on Days 1-28 of each 28-day cycle.
DRUGInavolisib (Dose #2)
Inavolisib tablets will be administered by mouth once daily.
DRUGInavolisib
Inavolisib tablets will be administered by mouth OD.
DRUGEmpagliflozin
Empagliflozin, administered orally, once daily (QD)
DRUGPalbociclib
For Empagliflozin + Inavolisib + Fulvestrant ± Palbociclib arm: Palbociclib 125 mg administered orally, QD in Cycle 1 followed by 125 mg on Days 1-21 of each cycle. For Metformin + Inavolisib + Fulvestrant ± Palbociclib arm: Palbociclib 125 mg administered orally, QD in Cycle 1, followed by 125 mg on Days 1-21 of each cycle (Cycle=28 days).
DRUGMetformin
Metf 1000 mg administered orally QD.
DRUGAtirmociclib
Atirmociclib administered orally, BID on Days 1-28 for each 28-day cycle.
Sponsors
Hoffmann-La Roche
Gilead Sciences
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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-naïve cohort): * Age \>/= 18 years at the time of signing Informed Consent Form * Eastern cooperative oncology group (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, unless archival tissue is available * 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR) | Baseline until disease progression or loss of clinical benefit (up to approximately 10 years) |
Secondary
| Measure | Time frame |
|---|---|
| Progression Free Survival (PFS) | Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (up to approximately 10 years) as determined by the investigator according to RECIST v1.1 |
| Disease Control Rate (DCR) | Baseline through end of study (up to approximately 10 years) |
| Overall Survival (OS) | Randomization to death from any cause, through the end of study (up to approximately 10 years) |
| Overall Survival (at specific time-points) | 12 and 18 months |
| Duration of Response (DOR) | Randomization until first occurrence of a documented objective response to the first recorded occurrence of disease progression or death from any cause (whichever occurs first), through end of study (up to approximately 10 years) |
| Percentage of Participants with Adverse Events | Baseline to end of study (up to approximately 10 years) |
Countries
Australia, France, Germany, Israel, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTReference Study ID Number: CO40115 https://forpatients.roche.com/
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed