A Phase II Study Evaluating the Efficacy and Safety of Inavolisib Plus Ribociclib Plus Fulvestrant Versus Placebo Plus Ribociclib Plus Fulvestrant in Participants With Advanced Breast Cancer

Roche

Status and phase: Enrolling; Phase 2

Conditions: Breast Cancer

Treatments: Drug: Inavolisib; Drug: Ribociclib; Drug: Fulvestrant; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07405801

2025-523013-28-00 (EU Trial (CTIS) Number)

CO46274

2025

Details and patient eligibility

About

A study to evaluate the efficacy and safety of triplet combination of inavolisib plus ribociclib and fulvestrant versus placebo plus ribociclib and fulvestrant in the first-line setting in participants with endocrine-therapy-resistant hormone receptor (HR)-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC).

Enrollment: 80 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Women or men with histologically or cytologically confirmed carcinoma of the breast that is locally advanced or metastatic and is not amenable to surgical or radiation therapy with curative intent
• Documented estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines, defined as >=1% of tumor cells stained positive based on the most recent tumor biopsy and assessed locally (Allison et al. 2020)
• Participants must not have received any prior systemic therapy for locally advanced unresectable or metastatic breast cancer (mBC) and must have progressed during adjuvant endocrine-based treatment or within 12 months after completing adjuvant endocrine-based therapy with an aromatase inhibitor or tamoxifen
• Confirmed biomarker eligibility as documented through central laboratory testing of a tumor tissue sample documenting both the lack of a phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit alpha gene (PIK3CA) mutation and the presence of heterozygous loss of chromosome 8p (i.e., PIK3CAnmd and chr8p loss)
• Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)

Exclusion criteria

• Metaplastic breast cancer
• Radiotherapy within 2 weeks before randomization
• Appropriate for treatment with cytotoxic chemotherapy at time of entry into the study, as per national or local treatment guidelines (e.g., participants with visceral crisis)
• Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
• Known and untreated, or active Central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). Participants with a history of treated CNS metastases are eligible
• Any history of leptomeningeal disease or carcinomatous meningitis

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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80 participants in 2 patient groups, including a placebo group

Inavolisib + Ribociclib + Fulvestrant

Experimental group

Description:

Participants will receive inavolisib, ribociclib and fulvestrant.

Treatment:

Drug: Fulvestrant

Drug: Ribociclib

Drug: Inavolisib

Placebo + Ribociclib + Fulvestrant

Placebo Comparator group

Description:

Participants will receive placebo, ribociclib and fulvestrant.

Treatment:

Drug: Placebo

Drug: Fulvestrant

Drug: Ribociclib