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

Phase 3

Active, not recruiting

• Conditions: Breast Cancer
• Interventions: Drug: Inavolisib; Drug: Fulvestrant; Drug: Alpelisib; Drug: Bupropion; Drug: Omeprazole; Drug: Midazolam

• Registration Number: NCT05646862
• Lead Sponsor: Hoffmann-La Roche

Brief 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).

Study Timeline

• Study First Submitted: 2022-12-02
• Study First Submitted QC: 2022-12-02
• Study First Posted: 2022-12-12
• Study Start: 2023-06-07
• Status Verified: 2025-11
• Last Update Submitted: 2025-11-03
• Last Update Posted: 2025-11-05
• Primary Completion: 2026-06-30
• Study Completion: 2029-03-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 420

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Inavolisib + Fulvestrant	Inavolisib	Participants will be administered the treatments as outlined in the interventions section.
Inavolisib + Fulvestrant	Fulvestrant	Participants will be administered the treatments as outlined in the interventions section.
Alpelisib + Fulvestrant	Fulvestrant	Participants will be administered the treatments as outlined in the interventions section.
Alpelisib + Fulvestrant	Alpelisib	Participants will be administered the treatments as outlined in the interventions section.
Sub-study: Inavolisib + Fulvestrant + CYP substrates	Inavolisib	Participants will be administered the treatments as outlined in the interventions section.
Sub-study: Inavolisib + Fulvestrant + CYP substrates	Fulvestrant	Participants will be administered the treatments as outlined in the interventions section.
Sub-study: Inavolisib + Fulvestrant + CYP substrates	Bupropion	Participants will be administered the treatments as outlined in the interventions section.
Sub-study: Inavolisib + Fulvestrant + CYP substrates	Omeprazole	Participants will be administered the treatments as outlined in the interventions section.
Sub-study: Inavolisib + Fulvestrant + CYP substrates	Midazolam	Participants will be administered the treatments as outlined in the interventions section.

Primary Outcome Measures

Name	Time	Method
Blinded Independent Central Review (BICR)-Assessed Progression Free Survival (PFS)	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	Day -4 and -3 of Cycle (C) 1, Day (D) 11 and C1D12. A cycle is 28 days.
Sub-study: Cmax for Bupropion	Day -3, -2, -1 of C1D1, C1D12, C1D13, C1D14 and C1D15. A cycle is 28 days.
Sub-study: Cmax for Omeprazole	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	Day -4 and -3 of C1D11 and C1D12. A cycle is 28 days.
Sub-study: AUC (0-last) for Bupropion	Day -3, -2, -1 of C1D1, C1D12, C1D13, C1D14 and C1D15. A cycle is 28 days.
Sub-study: AUC (0-last) for Omeprazole	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	Day -4 and -3 of C1D11 and C1D12. A cycle is 28 days.
Sub-study: AUC (0-infinity) for Bupropion	Day -3, -2, -1 of C1D1, C1D12, C1D13, C1D14 and C1D15. A cycle is 28 days.
Sub-study: AUC (0-infinity) for Omeprazole	Day -4 and -3 of C1D11 and C1D12. A cycle is 28 days.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	From randomization until death due to any cause (up to approximately 85 months)
BICR-Assessed Overall Response Rate (ORR)	Up to approximately 64 months
BICR-Assessed Best Overall Response (BOR)	Up to approximately 64 months
BICR-Assessed Clinical Benefit Rate (CBR)	Up to approximately 64 months
BICR-Assessed Duration of Response (DOR)	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	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	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	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)	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	Day 1 until 30 days after the final dose of study treatment (up to approximately 85 months)
Plasma Concentration of Inavolisib at Specified Timepoints	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	Day -4 until 30 days after the final dose of study treatment (up to approximately 85 months)

Trial Locations

Locations (146)

Icon Cancer Care Wesley; 🇦🇺 Auchenflower, Queensland, Australia

Instituto Nacional de Cancerologia; 🇲🇽 Distrito Federal, Mexico

Mount Vernon & Watford Hospital Trust; 🇬🇧 Northwood, United Kingdom

Cancer Blood and Specialty Clinic; 🇺🇸 Los Alamitos, California, United States

Los Angeles Cancer Network; 🇺🇸 Los Angeles, California, United States

UC Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States

Rocky Mountain Cancer Centers; 🇺🇸 Denver, Colorado, United States

Cleveland Clinic Florida; 🇺🇸 Weston, Florida, United States

Grady Health System; 🇺🇸 Atlanta, Georgia, United States

Midtown West Medical; 🇺🇸 Atlanta, Georgia, United States

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