A Phase 1/2 interventional study of Capecitabine and Atezolizumab in Metastatic Breast Cancer, sponsored by Hoffmann-La Roche. Recruiting at 53 sites in 9 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-10.
Sponsored by Hoffmann-La Roche · Phase 1/2, Interventional, and Treatment
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.
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):
Exclusion Criteria
Exclusion Criteria for Stage 1
Exclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-naïve cohort)
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.
Drug: Atezolizumab · Drug: Nab-Paclitaxel
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.
Drug: Atezolizumab · Drug: Tocilizumab · Drug: Nab-Paclitaxel
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.
Drug: Atezolizumab · Drug: Sacituzumab Govitecan
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.
Drug: Capecitabine
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.
Drug: Atezolizumab · Drug: Ipatasertib
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.
Drug: Atezolizumab · Drug: SGN-LIV1A
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.
Drug: Atezolizumab · Drug: Bevacizumab · Drug: Selicrelumab
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.
Drug: Atezolizumab · Drug: Chemotherapy (Gemcitabine + Carboplatin or Eribulin)
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.
Drug: Abemaciclib · Drug: Fulvestrant · Drug: Inavolisib (Dose #2)
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.
Drug: Fulvestrant · Drug: Ribociclib (Dose #1) · Drug: Inavolisib (Dose #2)
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.
Drug: Ribociclib (Dose #1) · Drug: Letrozole · Drug: Inavolisib (Dose #2)
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.
Drug: Fulvestrant · Drug: Ribociclib (Dose #2) · Drug: Inavolisib (Dose #2)
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.
Drug: Ribociclib (Dose #2) · Drug: Letrozole · Drug: Inavolisib (Dose #2)
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.
Drug: Abemaciclib · Drug: Letrozole · Drug: Inavolisib (Dose #2)
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.
Drug: Inavolisib (Dose #1) · Drug: 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.
Drug: Trastuzumab Deruxtecan · Drug: Inavolisib (Dose #2)
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.
Drug: Fulvestrant · Drug: Inavolisib (Dose #2) · Drug: Empagliflozin · Drug: 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.
Drug: Fulvestrant · Drug: Inavolisib (Dose #2) · Drug: Palbociclib · Drug: Metformin
Participants will receive inavolisib plus atirmociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
Drug: Fulvestrant · Drug: Inavolisib (Dose #2) · Drug: Atirmociclib
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.
Drug: Abemaciclib · Drug: Inavolisib (Dose #1) · Drug: Letrozole
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.
Drug: Abemaciclib · Drug: Inavolisib (Dose #1) · Drug: 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.
Drug: Abemaciclib · Drug: Inavolisib (Dose #2) · Drug: 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.
Drug: Ribociclib (Dose #1) · Drug: Inavolisib (Dose #2) · Drug: Giredestrant
Capecitabine will be administered 1250 milligrams per square meter (mg/m\^2) orally twice daily on Days 1-14 of each 21-day cycle.
Also known as: RO0091978
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.
Also known as: RO5541267
Ipatasertib will be administered by mouth 400 mg once a day, on Days 1-21 of each 28-day cycle.
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.
Also known as: RO7235441, Ladiratuzumab vedotin
Bevacizumab will be administered IV, 10 mg/kg, on Days 1 and 15 of each 28-day cycle.
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 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 will be administered IV, 8 mg/kg on Day 1 of each 28-day cycle.
Also known as: RO4877533
Nab-Paclitaxel will be administered IV, 100 mg/m\^2, on Days 1, 8, and 15 of each 28-day cycle.
Also known as: RO0247506
Sacituzumab govitecan will be administered by IV infusion, 10 mg/kg, on Days 1 and 8 of each 21-day cycle.
Also known as: RO7445735
Abemaciclib tablets will be administered at a dose of 150 mg twice daily by mouth on Days 1-28 of each 28-day cycle.
Also known as: RO7071651
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 tablets will be administered by mouth once daily.
Also known as: RO7072612
Inavolisib tablets will be administered by mouth once daily.
Also known as: GDC-0077, RO7113755
Trastuzumab Deruxtecan will be administered IV, 5.4 mg/kg on Day 1 of each 21-day cycle.
Ribociclib tablets will be administered by mouth once daily.
Also known as: RO7072612
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 tablets will be administered by mouth OD.
Also known as: GDC-0077, RO7113755
Empagliflozin, administered orally, once daily (QD)
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).
Metf 1000 mg administered orally QD.
Atirmociclib administered orally, BID on Days 1-28 for each 28-day cycle.
Giredestrant 30 mg will be administered by mouth once daily, on Days 1-28 of each 28-day cycle.
Objective Response Rate (ORR)
Time frame: Baseline until disease progression or loss of clinical benefit (up to approximately 12 years)
Progression Free Survival (PFS)
Time frame: 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 12 years) as determined by the investigator according to RECIST v1.1
Disease Control Rate (DCR)
Time frame: Baseline through end of study (up to approximately 12 years)
Overall Survival (OS)
Time frame: Randomization to death from any cause, through the end of study (up to approximately 12 years)
Overall Survival (at specific time-points)
Time frame: 12 and 18 months
Duration of Response (DOR)
Time frame: 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 12 years)
Percentage of Participants with Adverse Events
Time frame: Baseline to end of study (up to approximately 12 years)
Plan to share: Yes — For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing
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