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RecruitingInterventionalPhase 2

A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib Plus Ribociclib Plus Fulvestrant Versus Placebo Plus Ribociclib Plus Fulvestrant in Patients With Endocrine- Resistant Hormone-Receptor-Positive, HER2-Negative Advanced Breast Cancer With Chromosome 8P Loss and Without a PIK3CA Mutation

NCT ID: NCT07405801Sponsor: Hoffmann-La RocheLast updated: 2026-06-15

Summary

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).

Arms & interventions

  • DrugInavolisib

    Inavolisib will be administered as per the schedule mentioned in the protocol.

  • DrugRibociclib

    Ribociclib will be administered as per the schedule mentioned in the protocol.

  • DrugFulvestrant

    Fulvestrant will be administered as per the schedule mentioned in the protocol.

  • DrugPlacebo

    Placebo will be administered as per the schedule mentioned in the protocol.

Outcome measures

Primary

  • Percentage of Participants With Confirmed Objective Response (cORR)

    Time frame: Up to approximately 2 years

Secondary

  • Progression-Free Survival (PFS)

    Time frame: Up to approximately 2 years

  • Overall Survival (OS)

    Time frame: Up to approximately 2 years

  • Duration of Response (DOR)

    Time frame: Up to approximately 2 years

  • Percentage of Participants with Clinical Benefit (CBR)

    Time frame: Up to approximately 2 years

  • Percentage of Participants with Adverse Events (AEs)

    Time frame: Up to approximately 2 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)

    Time frame: Up to approximately 2 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)

    Time frame: Up to approximately 2 years

  • Change From Baseline in Symptomatic Treatment Toxicities as Assessed Through use of the PRO-CTCAE

    Time frame: Baseline, Up to approximately 2 years

  • Change from Baseline in Treatment Side-effect Bother as Assessed Through use of the FACT-G GP5 Item

    Time frame: Baseline, Up to approximately 2 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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

Study locations (6)

Avera Cancer Institute - Marshall

Marshall, Minnesota, 56258

Recruiting

Avera Cancer Institute - Aberdeen

Aberdeen, South Dakota, 57401

Recruiting

Avera Cancer Institute - Mitchell

Mitchell, South Dakota, 57301

Recruiting

Avera Cancer Institute - Pierre, SD

Pierre, South Dakota, 57501

Recruiting

Avera Cancer Institute

Sioux Falls, South Dakota, 57105

Recruiting

AMG Oncology and Hematology Avera Cancer Institute - Yankton

Yankton, South Dakota, 57078

Recruiting
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 | Cancerify