NCT06790693RecruitingPhase 3
A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib Plus a CDK4/6 Inhibitor and Letrozole Versus Placebo Plus a CDK4/6 Inhibitor and Letrozole in Patients With Endocrine-Sensitive PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 450
- Locations
- 243
- Primary Endpoint
- Progression-Free Survival (PFS)
Study Overview
Brief Summary
This study will evaluate the efficacy and safety of the combination of inavolisib plus a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) and letrozole versus placebo plus a CDK4/6i and letrozole in the first-line setting in participants with endocrine-sensitive PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced breast cancer (ABC).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Women or men with histologically or cytologically confirmed carcinoma of the breast
- •Documented ER-positive and/or progesterone receptor-positive tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines
- •Documented HER2-negative tumor according to ASCO/CAP guidelines
- •De-novo HR+ , HER2- ABC, or, alternatively, relapsed HR+ , HER2- ABC after at least 2 years of standard neoadjuvant/adjuvant endocrine therapy without disease progression during that treatment and disease-free interval of at least 1 year since the completion of that treatment
- •Participants who have bilateral breast cancers which are both HR-positive and HER2-negative
- •Confirmation of biomarker eligibility
- •Consent to provide fresh or archival tumor tissue specimen
- •Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Adequate hematologic and organ function within 14 days prior to initiation of study treatment
Exclusion Criteria
- •Pregnant or breastfeeding, or intention of becoming pregnant during the study or within the time frame in which contraception is required
- •Metaplastic breast cancer
- •Any prior systemic therapy for locally advanced unresectable or metastatic breast cancer
- •Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
- •Any history of leptomeningeal disease or carcinomatous meningitis
- •Known and untreated, or active CNS metastases. Participants with a history of treated CNS metastases are eligible
- •Active inflammatory or infectious conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye
- •Symptomatic active lung disease
- •History of or active inflammatory bowel disease
- •Any active bowel inflammation
- •Prior hematopoietic stem cell or bone marrow transplantation
- •Treatment with strong cytochrome P450 (CYP) 3A4 inhibitors or strong CYP3A4 inducers within 4 weeks or 5 drug-elimination half-lives, prior to initiation of study treatment
Arms & Interventions
Placebo + Letrozole + CDK4/6i
Placebo Comparator
Participants will receive placebo, letrozole and CDK4/6i.
Intervention: Placebo (Drug)
Inavolisib + Letrozole + CDK4/6i
Experimental
Participants will receive inavolisib, letrozole and CDK4/6i.
Intervention: Letrozole (Drug)
Inavolisib + Letrozole + CDK4/6i
Experimental
Participants will receive inavolisib, letrozole and CDK4/6i.
Intervention: Inavolisib (Drug)
Placebo + Letrozole + CDK4/6i
Placebo Comparator
Participants will receive placebo, letrozole and CDK4/6i.
Intervention: CDK4/6i (Drug)
Inavolisib + Letrozole + CDK4/6i
Experimental
Participants will receive inavolisib, letrozole and CDK4/6i.
Intervention: CDK4/6i (Drug)
Placebo + Letrozole + CDK4/6i
Placebo Comparator
Participants will receive placebo, letrozole and CDK4/6i.
Intervention: Letrozole (Drug)
Outcomes
Primary Outcomes
Progression-Free Survival (PFS)
Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 7 years)
Secondary Outcomes
- Change from Baseline in Symptomatic Treatment Toxicities as Assessed Through use of the PRO-CTCAE(Baseline up to 7 years)
- Number of Participants Reporting Each Response Option for Treatment Side-effect Bother Single-item General Population, Question 5 (GP5) from the Functional Assessment of Cancer Therapy-General Questionnaire; (FACT-G)(Up to 7 years)
- Overall Survival (OS)(From randomization to death from any cause (up to 7 years))
- Investigator-assessed Objective Response Rate (ORR)(Up to 7 years)
- Investigator-assessed Duration of Response (DOR)(From the first occurrence of a confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 7 years))
- Investigator-assessed Clinical Benefit Rate (CBR)(Up to 7 years)
- Time to Confirmed Deterioration (TTCD) in Pain(From baseline until end of follow-up (up to 7 years))
- TTCD in Physical Function(From baseline until end of follow-up (up to 7 years))
- TTCD in Role Function(From baseline until end of follow-up (up to 7 years))
- TTCD in Global Health Status(From baseline until end of follow-up (up to 7 years))
- Percentage of Participants with Adverse Events(From baseline until end of follow-up (up to 7 years))
- Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Treatment Toxicities Assessed by NCI Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Up to 7 years)
- Change from Baseline in Treatment Side-effect Bother as Assessed Through use of the FACT-G GP5 Item(Baseline up to 7 years)
Investigators
Study Sites (243)
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