A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer

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.

Conditions

• Metastatic Breast Cancer

Interventions

DRUG

Capecitabine

Capecitabine will be administered 1250 milligrams per square meter (mg/m\^2) orally twice daily on Days 1-14 of each 21-day cycle.

DRUG

Atezolizumab

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.

DRUG

Ipatasertib

Ipatasertib will be administered by mouth 400 mg once a day, on Days 1-21 of each 28-day cycle.

DRUG

SGN-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.

DRUG

Bevacizumab

Bevacizumab will be administered IV, 10 mg/kg, on Days 1 and 15 of each 28-day cycle.

DRUG

Chemotherapy (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.

DRUG

Selicrelumab

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).

DRUG

Tocilizumab

Tocilizumab will be administered IV, 8 mg/kg on Day 1 of each 28-day cycle.

DRUG

Nab-Paclitaxel

Nab-Paclitaxel will be administered IV, 100 mg/m\^2, on Days 1, 8, and 15 of each 28-day cycle.

DRUG

Sacituzumab Govitecan

Sacituzumab govitecan will be administered by IV infusion, 10 mg/kg, on Days 1 and 8 of each 21-day cycle.

DRUG

Abemaciclib

Abemaciclib tablets will be administered at a dose of 150 mg twice daily by mouth on Days 1-28 of each 28-day cycle.

DRUG

Fulvestrant

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.

DRUG

Ribociclib (Dose #1)

Ribociclib tablets will be administered by mouth once daily.

DRUG

Inavolisib (Dose #1)

Inavolisib tablets will be administered by mouth once daily.

DRUG

Trastuzumab Deruxtecan

Trastuzumab Deruxtecan will be administered IV, 5.4 mg/kg on Day 1 of each 21-day cycle.

DRUG

Ribociclib (Dose #2)

Ribociclib tablets will be administered by mouth once daily.

DRUG

Letrozole

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.

DRUG

Inavolisib (Dose #2)

Inavolisib tablets will be administered by mouth once daily.

DRUG

Inavolisib

Inavolisib tablets will be administered by mouth OD.

DRUG

Empagliflozin

Empagliflozin, administered orally, once daily (QD)

DRUG

Palbociclib

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).

DRUG

Metformin

Metf 1000 mg administered orally QD.

DRUG

Atirmociclib

Atirmociclib administered orally, BID on Days 1-28 for each 28-day cycle.

Sponsors & Collaborators

• Gilead Sciences

  collaborator INDUSTRY

• Pfizer

  collaborator INDUSTRY

• Hoffmann-La Roche

  lead INDUSTRY

Principal Investigators

• Clinical Trials · Hoffmann-La Roche

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-03-30

Primary Completion

2030-09-30

Completion

2030-09-30

FDA Drug

Yes

Countries

• United States
• Australia
• France
• Germany
• Israel
• South Korea
• Spain
• Taiwan
• United Kingdom

Study Locations