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Metastatic Breast CancerGeneticsCancerWomen's healthDrugPhase 1, Phase 2

What this study is

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, seven 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, 6 and 7 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.

What's being tested

  • Capecitabine

    Intervention · DRUG

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

  • Atezolizumab

    Intervention · DRUG

    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.

  • Ipatasertib

    Intervention · DRUG

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

  • SGN-LIV1A

    Intervention · DRUG

    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.

  • Bevacizumab

    Intervention · DRUG

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

  • Chemotherapy (Gemcitabine + Carboplatin or Eribulin)

    Intervention · DRUG

    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.

  • Selicrelumab

    Intervention · DRUG

    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).

  • Tocilizumab

    Intervention · DRUG

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

  • Nab-Paclitaxel

    Intervention · DRUG

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

  • Sacituzumab Govitecan

    Intervention · DRUG

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

  • Abemaciclib

    Intervention · DRUG

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

  • Fulvestrant

    Intervention · DRUG

    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.

  • Ribociclib (Dose #1)

    Intervention · DRUG

  • Inavolisib (Dose #1)

    Intervention · DRUG

    Inavolisib tablets will be administered by mouth once daily.

  • Trastuzumab Deruxtecan

    Intervention · DRUG

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

  • Ribociclib (Dose #2)

    Intervention · DRUG

  • Letrozole

    Intervention · DRUG

    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.

  • Inavolisib (Dose #2)

    Intervention · DRUG

    Inavolisib tablets will be administered by mouth OD.

  • Empagliflozin

    Intervention · DRUG

    Empagliflozin, administered orally, once daily (QD)

  • Palbociclib

    Intervention · DRUG

    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).

  • Metformin

    Intervention · DRUG

    Metf 1000 mg administered orally QD.

  • Atirmociclib

    Intervention · DRUG

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

  • Giredestrant

    Intervention · DRUG

    Giredestrant 30 mg will be administered by mouth once daily, on Days 1-28 of each 28-day cycle.

Both Ribociclib (Dose #1) and Ribociclib (Dose #2)

Ribociclib tablets will be administered by mouth once daily.

Study details

Official title
A Phase Ib/II, Open-label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic Breast Cancer (Morpheus-panBC)
Sponsor
Hoffmann-La Roche
Conditions
Metastatic Breast Cancer
Enrolling
1,132 people
Starts
2018-03-30
Est. completion
2030-09-30
Design
Open-label, randomized, parallel groups, Phase 1, Phase 2
Record
View on ClinicalTrials.gov ↗