NCT05646862

A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy

A Phase III, Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Versus Alpelisib Plus Fulvestrant in Patients With Hormone Receptor-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Who Progressed During or After CDK4/6 Inhibitor and Endocrine Combination Therapy

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 420 (estimated)
• Sponsor: Hoffmann-La Roche · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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).

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	Inavolisib	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.
DRUG	Fulvestrant	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.
DRUG	Alpelisib	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.
DRUG	Bupropion	Participants will be administered bupropion PO on Day -3 and Day 12 of Cycle 1 of the sub-study.
DRUG	Omeprazole	Participants will be administered omerprazole PO on Day -4 and Day 11 of Cycle 1 of sub-study.
DRUG	Midazolam	Participants will be administered midazolam PO on Day -4 and Day 11 of Cycle 1 of sub-study.

Timeline

• Start date: 2023-06-07
• Primary completion: 2026-04-06
• Completion: 2029-03-30
• First posted: 2022-12-12
• Last updated: 2026-02-05

Locations

145 sites across 18 countries: United States, Argentina, Australia, Belgium, Brazil, Canada, China, France, Germany, Italy, Mexico, Poland, South Africa, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom

Regulatory

• FDA-regulated drug study