Recruiting
Phase 1
Phase 2

Breast Cancer Combinations

Sponsor:

Hoffmann-La Roche

Code:

NCT03424005

Conditions

Metastatic Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Capecitabine

Atezolizumab

Ipatasertib

SGN-LIV1A

Bevacizumab

Study Details

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, 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.

Conditions

Metastatic Breast Cancer

Study ID

NCT03424005

Start date

Mar 30, 2018

Status verified date

Aug, 2026

Completion date

Sep 30, 2030

Anticipated

Primary completion date

Sep 30, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 adenocarcinoma of the breast
  • 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

Exclusion Criteria

Exclusion Criteria for Stage 1

  • Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, CD40 agonists or interleukin-2 (IL-2) or IL-2-like compounds
  • Biologic treatment (e.g., bevacizumab) within 2 weeks prior to initiation of study treatment, or other systemic treatment for TNBC within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
  • Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study
  • Eligibility only for the control arm

Exclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-naïve cohort)

  • Adverse events from prior anti-cancer therapy that have not resolved to Grade </= 1 or better with the exception of alopecia of any grade and Grade </= 2 peripheral neuropathy
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
  • Uncontrolled tumor-related pain
  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
  • History of leptomeningeal disease
  • Active or history of autoimmune disease or immune deficiency
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Active tuberculosis
  • Severe infection within 4 weeks prior to initiation of study treatment
  • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
  • Significant cardiovascular disease
  • Prior allogeneic stem cell or solid organ transplantation
  • History of malignancy other than breast cancer within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death
  • Pregnancy or breastfeeding, or intention of becoming pregnant during the study

Study Design

Enrollment

1132 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

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.

Interventions

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.

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.

Ipatasertib

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

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.

Bevacizumab

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

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.

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).

Tocilizumab

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

Nab-Paclitaxel

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

Sacituzumab Govitecan

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

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.

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.

Ribociclib (Dose #1)

Ribociclib tablets will be administered by mouth once daily.

Inavolisib (Dose #1)

Inavolisib tablets will be administered by mouth once daily.

Trastuzumab Deruxtecan

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

Ribociclib (Dose #2)

Ribociclib tablets will be administered by mouth once daily.

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.

Inavolisib (Dose #2)

Inavolisib tablets will be administered by mouth OD.

Empagliflozin

Empagliflozin, administered orally, once daily (QD)

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).

Metformin

Metf 1000 mg administered orally QD.

Atirmociclib

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

Giredestrant

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

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 and Locations

Central contacts

Reference Study ID Number: CO40115 https://forpatients.roche.com/ No attachments to email below.

888-662-6728 (U.S. and Canada)global-roche-genentech-trials@gene.com

Locations

University of California San Diego (UCSD) - Koman Family Outpatient Pavilion ? La Jolla

Recruiting

La Jolla, California, United States, 92093-1350

Metro-Minnesota Community Oncology Research Consortium

Recruiting

Saint Paul, Minnesota, United States, 55101-2502

Renown Regional Medical Center

Recruiting

Reno, Nevada, United States, 89502-1576

Duke Cancer Institute

Recruiting

Durham, North Carolina, United States, 27710-2000

Tennessee Oncology - Chattanooga Oncology & Hematology Associates

Recruiting

Chattanooga, Tennessee, United States, 37404

The West Clinic

Recruiting

Germantown, Tennessee, United States, 38138

Tennessee Oncology PLLC

Recruiting

Nashville, Tennessee, United States, 37203

Vanderbilt University Medical Center

Recruiting

Nashville, Tennessee, United States, 37212

More Information

Sponsor

Hoffmann-La Roche

Last update posted

Aug 12, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-04. This information was provided to ClinicalTrials.gov by Hoffmann-La Roche on 2026-08-12.