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

NCT07405801 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: CO462742025-523013-28-00
• Study Type: interventional
• Target: 80
• Locations: 10 countries
• Sites: 36

Brief 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).

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Confirmed Objective Response (cORR)

  Up to approximately 2 years

Secondary Outcomes (9)

• Progression-Free Survival (PFS)

  Up to approximately 2 years

• Overall Survival (OS)

  Up to approximately 2 years

• Duration of Response (DOR)

  Up to approximately 2 years

• Percentage of Participants with Clinical Benefit (CBR)

  Up to approximately 2 years

• Percentage of Participants with Adverse Events (AEs)

  Up to approximately 2 years

Study Arms (2)

Inavolisib + Ribociclib + Fulvestrant

EXPERIMENTAL

Participants will receive inavolisib, ribociclib and fulvestrant.

Drug: Inavolisib; Drug: Ribociclib; Drug: Fulvestrant

Placebo + Ribociclib + Fulvestrant

PLACEBO COMPARATOR

Participants will receive placebo, ribociclib and fulvestrant.

Drug: Ribociclib; Drug: Fulvestrant; Drug: Placebo

Interventions

Inavolisib DRUG

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

Inavolisib + Ribociclib + Fulvestrant

Ribociclib DRUG

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

Inavolisib + Ribociclib + Fulvestrant; Placebo + Ribociclib + Fulvestrant

Fulvestrant DRUG

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

Inavolisib + Ribociclib + Fulvestrant; Placebo + Ribociclib + Fulvestrant

Placebo DRUG

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

Placebo + Ribociclib + Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (36)

Avera Cancer Institute - Marshall

Marshall, Minnesota, 56258, United States

RECRUITING

Avera Cancer Institute - Aberdeen

Aberdeen, South Dakota, 57401, United States

RECRUITING

Avera Cancer Institute - Mitchell

Mitchell, South Dakota, 57301, United States

RECRUITING

Avera Cancer Institute - Pierre, SD

Pierre, South Dakota, 57501, United States

RECRUITING

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

RECRUITING

AMG Oncology and Hematology Avera Cancer Institute - Yankton

Yankton, South Dakota, 57078, United States

RECRUITING

Centro Oncologico Korben

Caba, C1426AGE, Argentina

RECRUITING

Centro Médico Fleischer

Capital Federal, C1414, Argentina

RECRUITING

Sanatorio de la Mujer

Rosario, S2000ORE, Argentina

RECRUITING

Hospital Santa Rita de Cassia Vitoria

Vitória, Espírito Santo, 29043-260, Brazil

RECRUITING

Hospital Brasilia

Brasília, Federal District, 71.635-610, Brazil

RECRUITING

ICTR Curitiba

Curitiba, Paraná, 80510-130, Brazil

RECRUITING

Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda

São Paulo, São Paulo, 01317-000, Brazil

RECRUITING

CIUSSS du Saguenay Lac-Saint-Jean, Chicoutimi Hospital

Chicoutimi, Quebec, G7H 5H6, Canada

RECRUITING

McGill University

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Centre Leon Berard

Lyon, 69008, France

RECRUITING

Istituto Nazionale Tumori Irccs Fondazione g. PASCALE

Naples, Campania, 80131, Italy

RECRUITING

IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola

Meldola, Emilia-Romagna, 47014, Italy

RECRUITING

Università Campus Bio-Medico di Roma

Rome, Lazio, 128, Italy

RECRUITING

Asst Papa Giovanni XXIII

Bergamo, Lombardy, 24127, Italy

RECRUITING

Ospedale San Raffaele

Milan, Lombardy, 20132, Italy

RECRUITING

Irccs Istituto Nazionale Dei Tumori (Int)

Milan, Lombardy, 20133, Italy

RECRUITING

Bialostockie Centrum Onkologii

Bialystok, 15-027, Poland

RECRUITING

COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej

Lublin, 20-090, Poland

RECRUITING

Dolno?l?skie Centrum Onkologii

Wroc?aw, 53-413, Poland

RECRUITING

Soon Chun Hyang University Cheonan Hospital

Dongnam-gu, Cheonan-si, 31151, South Korea

RECRUITING

Gachon University Gil Medical Center

Namdong-Gu, 21565, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, 13605, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Hospital Clinic I Provincial

Barcelona, 08036, Spain

RECRUITING

Hospital Universitario Clínico San Cecilio

Granada, 18016, Spain

RECRUITING

Hospital Ramon y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

Leicester Royal Infirmary

Leicester, LE1 5WWi, United Kingdom

RECRUITING

Christie Hospital Nhs Trust

Manchester, M20 4GJ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

inavolisib; ribociclib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: CO46274 https://forpatients.roche.com/

CONTACT

888-662-6728; global-roche-genentech-trials@gene.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2026
• First Posted: February 12, 2026
• Study Start: April 7, 2026
• Primary Completion (Estimated): December 19, 2028
• Study Completion (Estimated): February 26, 2030
• Last Updated: May 18, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

BR (4); CA (2); KR (4); US (6); ES (5); AR (3); FR (1); IT (6); PL (3); GB (2)