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

Conditions

• Metastatic Breast Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Capecitabine — 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 — 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 — DRUG
  Ipatasertib will be administered by mouth 400 mg once a day, on Days 1-21 of each 28-day cycle.
• SGN-LIV1A — 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 — DRUG
  Bevacizumab will be administered IV, 10 mg/kg, on Days 1 and 15 of each 28-day cycle.
• Chemotherapy (Gemcitabine + Carboplatin or Eribulin) — 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 — 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 — DRUG
  Tocilizumab will be administered IV, 8 mg/kg on Day 1 of each 28-day cycle.
• Nab-Paclitaxel — DRUG
  Nab-Paclitaxel will be administered IV, 100 mg/m\^2, on Days 1, 8, and 15 of each 28-day cycle.
• Sacituzumab Govitecan — DRUG
  Sacituzumab govitecan will be administered by IV infusion, 10 mg/kg, on Days 1 and 8 of each 21-day cycle.
• Abemaciclib — 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 — 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) — DRUG
  Ribociclib tablets will be administered by mouth once daily.
• Inavolisib (Dose #1) — DRUG
  Inavolisib tablets will be administered by mouth once daily.
• Trastuzumab Deruxtecan — DRUG
  Trastuzumab Deruxtecan will be administered IV, 5.4 mg/kg on Day 1 of each 21-day cycle.
• Ribociclib (Dose #2) — DRUG
  Ribociclib tablets will be administered by mouth once daily.
• Letrozole — 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) — DRUG
  Inavolisib tablets will be administered by mouth OD.
• Empagliflozin — DRUG
  Empagliflozin, administered orally, once daily (QD)
• Palbociclib — 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 — DRUG
  Metf 1000 mg administered orally QD.
• Atirmociclib — DRUG
  Atirmociclib administered orally, BID on Days 1-28 for each 28-day cycle.
• Giredestrant — DRUG
  Giredestrant 30 mg will be administered by mouth once daily, on Days 1-28 of each 28-day cycle.

Study Details

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.

Key Dates

Start date

Mar 30, 2018

Status verified

Jun 2026

Primary completion

Sep 30, 2030

Completion

Sep 30, 2030

Study Design

Enrollment

1,132 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Atezolizumab + Nab-Paclitaxel
  1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab plus nab-paclitaxel until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed.
• Experimental: Atezolizumab + Nab-Paclitaxel + Tocilizumab
  1L PD-L1-positive participants will receive combination treatment with atezolizumab plus nab-paclitaxel and tocilizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed and participant follow-up is complete.
• Experimental: Atezolizumab + Sacituzumab Govitecan
  1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab plus sacituzumab govitecan until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed.
• Active Comparator: Capecitabine
  2L CIT-naïve participants will receive capecitabine until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1). Participants who progressed on treatment may have the option of receiving atezolizumab along with chemotherapy (chemo) during stage 2, provided they meet the eligibility criteria. Enrollment is closed and participant follow-up is complete.
• Experimental: Atezolizumab + Ipatasertib
  2L CIT-naïve participants will receive doublet combination treatment with atezolizumab plus ipatasertib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed and participant follow-up is complete.
• Experimental: Atezolizumab + SGN-LIV1A
  2L CIT-naïve participants will receive doublet combination treatment with atezolizumab plus SGNLIV1A until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Patients who experience loss of clinical benefit as determined by the investigator or unacceptable toxicity related to SGN-LIV1A will be given the option of receiving Atezolizumab + chemo during Stage 2, provided they meet the eligibility criteria. Enrollment is closed and participant follow-up is complete.
• Experimental: Atezolizumab + Selicrelumab + Bevacizumab
  2L-CIT-naïve participants will receive doublet combination treatment with atezolizumab plus selicrelumab and bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed and participant follow-up is complete.
• Experimental: Atezolizumab + Chemo (Gemcitabine + Carboplatin or Eribulin)
  2L CIT-naïve participants enrolled in the active comparator arm who experience disease progression per RECIST v1.1 and 2L CIT-naïve participants enrolled in an experimental arm who experience loss of clinical benefit as determined by the investigator may receive doublet combination treatment with atezolizumab plus chemo (gemcitabine + carboplatin or eribulin) until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed and participant follow-up is complete.
• Experimental: Inavolisib (Dose #2) + Abemaciclib + Fulvestrant
  HR+ participants will receive treatment with inavolisib plus abemaciclib plus fulvestrant until unacceptable toxicity or disease progression determined by the investigator according to RECIST v1.1.
• Experimental: Inavolisib (Dose #2) + Ribociclib (Dose #1) + Fulvestrant
  HR+ participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
• Experimental: Inavolisib (Dose #2) + Ribociclib (Dose #1) + Letrozole
  HR+ participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
• Experimental: Inavolisib (Dose #2) + Ribociclib (Dose #2) + Fulvestrant
  HR+ participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
• Experimental: Inavolisib (Dose #2) + Ribociclib (Dose #2) + Letrozole
  HR+ participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
• Experimental: Inavolisib (Dose #2) + Abemaciclib + Letrozole
  HR+ participants will receive treatment with inavolisib plus abemaciclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
• Experimental: Inavolisib (Dose #1) + Trastuzumab Deruxtecan
  HER2+/HER2-low participants will receive inavolisib + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. Enrollment is closed.
• Experimental: Inavolisib (Dose #2) + Trastuzumab Deruxtecan
  HER2+/HER2-low participants will receive inavolisib + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. Enrollment is closed.
• Experimental: Empagliflozin + Inavolisib (Dose #2) + Fulvestrant ± Palbociclib
  Participants with locally advanced or metastatic, HR+, HER2- participants will receive empagliflozin plus inavolisib plus fulvestrant with or without palbociclib until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
• Experimental: Metformin + Inavolisib (Dose #2) + Fulvestrant ± Palbociclib
  Participants with locally advanced or metastatic, HR+, HER2- participants will receive metformin plus inavolisib plus fulvestrant with or without palbociclib until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
• Experimental: Inavolisib (Dose #2) + Atirmociclib (Atirmo) + Fulvestrant
  Participants will receive inavolisib plus atirmociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
• Experimental: Inavolisib (Dose #1) + Abemaciclib + Letrozole
  HR+ participants will receive treatment with inavolisib plus abemaciclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
• Experimental: Inavolisib (Dose #1) + Abemaciclib + Giredestrant
  HR+ participants will receive treatment with inavolisib plus abemaciclib plus giredestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
• Experimental: Inavolisib (Dose #2) + Abemaciclib + Giredestrant
  HR+ participants will receive treatment with inavolisib plus abemaciclib plus giredestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
• Experimental: Inavolisib (Dose #2) + Ribociclib (Dose #1) + Giredestrant
  HR+ participants will receive treatment with inavolisib plus ribociclib plus giredestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

Primary Outcome Measure

Objective Response Rate (ORR) [ Time Frame: Baseline until disease progression or loss of clinical benefit (up to approximately 12 years) ]

Central Contacts

• Reference Study ID Number: CO40115 https://forpatients.roche.com/
  888-662-6728 (U.S. and Canada)
  [email protected]

Locations (17)

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