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

May 14, 2026 updated by: Hoffmann-La Roche

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Argentina
      • Caba, Argentina, C1426AGE
        • Recruiting
        • Centro Oncologico Korben
      • Capital Federal, Argentina, C1414
        • Recruiting
        • Centro Medico Fleischer
      • Rosario, Argentina, S2000ORE
        • Recruiting
        • Sanatorio de la Mujer
  • Brazil
    • Espírito Santo
      • Vitória, Espírito Santo, Brazil, 29043-260
        • Recruiting
        • Hospital Santa Rita de Cassia Vitoria
    • Federal District
      • Brasília, Federal District, Brazil, 71.635-610
        • Recruiting
        • Hospital Brasilia
    • Paraná
      • Curitiba, Paraná, Brazil, 80510-130
        • Recruiting
        • ICTR Curitiba
    • São Paulo
      • São Paulo, São Paulo, Brazil, 01317-000
        • Recruiting
        • Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
  • Canada
    • Quebec
      • Chicoutimi, Quebec, Canada, G7H 5H6
        • Recruiting
        • CIUSSS du Saguenay Lac-Saint-Jean, Chicoutimi Hospital
      • Montreal, Quebec, Canada, H4A 3J1
        • Recruiting
        • McGill University
  • France
      • Lyon, France, 69008
        • Recruiting
        • Centre Leon Berard
  • Italy
    • Campania
      • Naples, Campania, Italy, 80131
        • Recruiting
        • Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
    • Emilia-Romagna
      • Meldola, Emilia-Romagna, Italy, 47014
        • Recruiting
        • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
    • Lazio
      • Rome, Lazio, Italy, 128
        • Recruiting
        • Università Campus Bio-Medico di Roma
    • Lombardy
      • Bergamo, Lombardy, Italy, 24127
        • Recruiting
        • ASST Papa Giovanni XXIII
      • Milan, Lombardy, Italy, 20132
        • Recruiting
        • Ospedale San Raffaele
      • Milan, Lombardy, Italy, 20133
        • Recruiting
        • Irccs Istituto Nazionale Dei Tumori (Int)
  • Poland
      • Bialystok, Poland, 15-027
        • Recruiting
        • Bialostockie Centrum Onkologii
      • Lublin, Poland, 20-090
        • Recruiting
        • COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej
      • Wroc?aw, Poland, 53-413
        • Recruiting
        • Dolno?l?skie Centrum Onkologii
  • South Korea
      • Dongnam-gu, Cheonan-si, South Korea, 31151
        • Recruiting
        • Soon Chun Hyang University Cheonan Hospital
      • Namdong-Gu, South Korea, 21565
        • Recruiting
        • Gachon University Gil Medical Center
      • Seongnam-si, South Korea, 13605
        • Recruiting
        • Seoul National University Bundang Hospital
      • Seoul, South Korea, 03080
        • Recruiting
        • Seoul National University Hospital
  • Spain
      • Barcelona, Spain, 08036
        • Recruiting
        • Hospital Clinic I Provincial
      • Granada, Spain, 18016
        • Recruiting
        • Hospital Universitario Clínico San Cecilio
      • Madrid, Spain, 28041
        • Recruiting
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28034
        • Recruiting
        • Hospital Ramon y Cajal
      • Valencia, Spain, 46010
        • Recruiting
        • Hospital Clinico Universitario de Valencia
  • United Kingdom
      • Leicester, United Kingdom, LE1 5WWi
        • Recruiting
        • Leicester Royal Infirmary
      • Manchester, United Kingdom, M20 4GJ
        • Recruiting
        • Christie Hospital Nhs Trust
  • United States
    • Minnesota
      • Marshall, Minnesota, United States, 56258
        • Recruiting
        • Avera Cancer Institute - Marshall
    • South Dakota
      • Aberdeen, South Dakota, United States, 57401
        • Recruiting
        • Avera Cancer Institute - Aberdeen
      • Mitchell, South Dakota, United States, 57301
        • Recruiting
        • Avera Cancer Institute - Mitchell
      • Pierre, South Dakota, United States, 57501
        • Recruiting
        • Avera Cancer Institute - Pierre, SD
      • Sioux Falls, South Dakota, United States, 57105
        • Recruiting
        • Avera Cancer Institute
      • Yankton, South Dakota, United States, 57078
        • Recruiting
        • AMG Oncology and Hematology Avera Cancer Institute - Yankton

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Inavolisib + Ribociclib + Fulvestrant
Participants will receive inavolisib, ribociclib and fulvestrant.
Drug: Inavolisib
Inavolisib will be administered as per the schedule mentioned in the protocol.
Drug: Ribociclib
Ribociclib will be administered as per the schedule mentioned in the protocol.
Drug: Fulvestrant
Fulvestrant will be administered as per the schedule mentioned in the protocol.
Placebo Comparator: Placebo + Ribociclib + Fulvestrant
Participants will receive placebo, ribociclib and fulvestrant.
Drug: Ribociclib
Ribociclib will be administered as per the schedule mentioned in the protocol.
Drug: Fulvestrant
Fulvestrant will be administered as per the schedule mentioned in the protocol.
Drug: Placebo
Placebo will be administered as per the schedule mentioned in the protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percentage of Participants With Confirmed Objective Response (cORR)
Time Frame: Up to approximately 2 years
Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Duration of Response (DOR)
Time Frame: Up to approximately 2 years
Up to approximately 2 years
Progression-Free Survival (PFS)
Time Frame: Up to approximately 2 years
Up to approximately 2 years
Overall Survival (OS)
Time Frame: Up to approximately 2 years
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
Baseline, Up to approximately 2 years
Percentage of Participants with Clinical Benefit (CBR)
Time Frame: Up to approximately 2 years
Up to approximately 2 years
Percentage of Participants with Adverse Events (AEs)
Time Frame: Up to approximately 2 years
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
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
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
Baseline, Up to approximately 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 7, 2026

Primary Completion (Estimated)

December 19, 2028

Study Completion (Estimated)

February 26, 2030

Study Registration Dates

First Submitted

February 6, 2026

First Submitted That Met QC Criteria

February 6, 2026

First Posted (Actual)

February 12, 2026

Study Record Updates

Last Update Posted (Actual)

May 18, 2026

Last Update Submitted That Met QC Criteria

May 14, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CO46274
  • 2025-523013-28-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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