A Phase 3 interventional study of Inavolisib and Fulvestrant in Breast Cancer, sponsored by Hoffmann-La Roche. Recruiting at 210 sites in 20 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-28.
Sponsored by Hoffmann-La Roche · Phase 3, Interventional, and Treatment
This is a Phase III, multicenter, randomized, open-label, global study designed to evaluate the efficacy and safety of inavolisib plus fulvestrant compared with alpelisib plus fulvestrant in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) -negative, PIK3CA-mutated, locally advanced (LA) or metastatic breast cancer (mBC), who progressed during or after cyclin dependent kinase 4/6i (CDK4/6i)-based therapy.
Enrollment for the main study is now complete.
The drug-drug interaction (DDI) substudy will evaluate the impact of repeat doses of inavolisib (coadministered with fulvestrant) on single-dose pharmacokinetics of sensitive CYP450 enzyme substrates (midazolam, omeprazole and bupropion) in participants with hormone receptor (HR)-positive, HER2-negative, PIK3CA-mutated, locally advanced (LA) or metastatic breast cancer (mBC), who progressed during or after CDK4/6 inhibitor (CDK4/6i) in combination with endocrine therapy (ET).
Enrollment for the substudy is now open to recruitment.
Inclusion Criteria for Main Study and Sub-study:
Exclusion Criteria for both Main Study and Sub-study:
Exclusion Criteria for Main Study Only:
Exclusion Criteria for Sub-study Only:
Participants will be administered the treatments as outlined in the interventions section.
Drug: Inavolisib · Drug: Fulvestrant
Participants will be administered the treatments as outlined in the interventions section.
Drug: Fulvestrant · Drug: Alpelisib
Participants will be administered the treatments as outlined in the interventions section.
Drug: Inavolisib · Drug: Fulvestrant · Drug: Bupropion · Drug: Omeprazole · Drug: Midazolam
Participants will be administered a 9 milligram (mg) inavolisib tablet orally once a day (PO QD) on Days 1-28 of each 28-day cycle of main study and sub-study.
Participants will be administered 500 mg of fulvestrant on Days 1 and 15 of Cycle 1 and then on Day 1 of each subsequent 28-day cycle of main study and sub-study.
Alpelisib will be administered to participants at the approved dose in combination with fulvestrant: 300 mg taken PO QD and on days 1-28 of each 28-day cycle.
Participants will be administered bupropion PO on Day -3 and Day 12 of Cycle 1 of the sub-study.
Participants will be administered omerprazole PO on Day -4 and Day 11 of Cycle 1 of sub-study.
Participants will be administered midazolam PO on Day -4 and Day 11 of Cycle 1 of sub-study.
Blinded Independent Central Review (BICR)-Assessed Progression Free Survival (PFS)
Time frame: From randomization until disease progression or death due to any cause (up to approximately 64 months)
Sub-study: Maximum observed Drug Concentration (Cmax) for Midazolam
Time frame: Day -4 and -3 of Cycle (C) 1, Day (D) 11 and C1D12. A cycle is 28 days.
Sub-study: Cmax for Bupropion
Time frame: Day -3, -2, -1 of C1D1, C1D12, C1D13, C1D14 and C1D15. A cycle is 28 days.
Sub-study: Cmax for Omeprazole
Time frame: Day -4 and -3 of C1D11 and C1D12. A cycle is 28 days.
Sub-study: Area Under the Concentration-Time Curve From Time 0 to Last Measurable Concentration (AUC [0-last]) for Midazolam
Time frame: Day -4 and -3 of C1D11 and C1D12. A cycle is 28 days.
Sub-study: AUC (0-last) for Bupropion
Time frame: Day -3, -2, -1 of C1D1, C1D12, C1D13, C1D14 and C1D15. A cycle is 28 days.
Sub-study: AUC (0-last) for Omeprazole
Time frame: Day -4 and -3 of C1D11 and C1D12. A cycle is 28 days.
Sub-study: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) for Midazolam
Time frame: Day -4 and -3 of C1D11 and C1D12. A cycle is 28 days.
Sub-study: AUC (0-infinity) for Bupropion
Time frame: Day -3, -2, -1 of C1D1, C1D12, C1D13, C1D14 and C1D15. A cycle is 28 days.
Sub-study: AUC (0-infinity) for Omeprazole
Time frame: Day -4 and -3 of C1D11 and C1D12. A cycle is 28 days.
Overall survival (OS)
Time frame: From randomization until death due to any cause (up to approximately 85 months)
BICR-Assessed Overall Response Rate (ORR)
Time frame: Up to approximately 64 months
BICR-Assessed Best Overall Response (BOR)
Time frame: Up to approximately 64 months
BICR-Assessed Clinical Benefit Rate (CBR)
Time frame: Up to approximately 64 months
BICR-Assessed Duration of Response (DOR)
Time frame: From CR or PR until disease progression or death due to any cause (up to approximately 64 months)
Time to Confirmed Deterioration (TTCD) in Pain
Time frame: Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit (up to approximately 85 months). Each cycle is 28 days.
TTCD in Physical Functioning
Time frame: Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit (up to approximately 85 months). Each cycle is 28 days.
TTCD in Role Functioning
Time frame: Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit (up to approximately 85 months). Each cycle is 28 days.
TTCD in Global Health Status/Quality of Life (QOL)
Time frame: Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit (up to approximately 85 months). Each cycle is 28 days.
Percentage of Participants with Adverse Events
Time frame: Day 1 until 30 days after the final dose of study treatment (up to approximately 85 months)
Plasma Concentration of Inavolisib at Specified Timepoints
Time frame: Day 1 and 15 of Cycle 1, and Day 1 of Cycles 2 and 3. Each cycle is 28 days.
Sub-study: Percentage of Participants with Adverse Events
Time frame: Day -4 until 30 days after the final dose of study treatment (up to approximately 85 months)
Showing the first 100 of 210 sites across 20 countries.
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
No publications or documents are linked to this record.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Hoffmann-La Roche