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

Official title

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

Overview

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).

Interventions

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

Primary outcome measures

• Percentage of Participants With Confirmed Objective Response (cORR) [Time frame: Up to approximately 2 years]

Secondary outcome measures (9)

• 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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 6 centers

• Avera Cancer Institute - Marshall — Marshall
• Avera Cancer Institute - Aberdeen — Aberdeen
• Avera Cancer Institute - Mitchell — Mitchell
• Avera Cancer Institute - Pierre, SD — Pierre
• Avera Cancer Institute — Sioux Falls
• AMG Oncology and Hematology Avera Cancer Institute - Yankton — Yankton

Italy · 6 centers

• Istituto Nazionale Tumori Irccs Fondazione g. PASCALE — Naples
• IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola — Meldola
• Università Campus Bio-Medico di Roma — Rome
• Asst Papa Giovanni XXIII — Bergamo
• Ospedale San Raffaele — Milan
• Irccs Istituto Nazionale Dei Tumori (Int) — Milan

Spain · 6 centers

• ICO L'Hospitalet — L'Hospitalet de Llobregat
• Hospital Clinic Barcelona — Barcelona
• Hospital Universitario Clínico San Cecilio — Granada
• Hospital Ramon y Cajal — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Clinico Universitario de Valencia — Valencia

France · 5 centers

• Centre Oscar Lambret — Lille
• Centre Leon Berard — Lyon
• Institut Paoli Calmettes — Marseille
• Institut Régional du Cancer de Montpellier — Montpellier
• Institut Universitaire du Cancer - Oncopole Toulouse (IUCT-O) — Toulouse

Argentina · 4 centers

• Inst. Alexander Fleming — Buenos Aires
• Centro Oncologico Korben — Caba
• Centro Médico Fleischer — Capital Federal
• Sanatorio de la Mujer — Rosario

Brazil · 4 centers

• Hospital Santa Rita de Cassia Vitoria — Vitória
• Hospital Brasilia — Brasília
• ICTR Curitiba — Curitiba
• Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda — São Paulo

Poland · 4 centers

• Instytut "Centrum Zdrowia Matki Polki" — ?ód?
• Bialostockie Centrum Onkologii — Bialystok
• COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej — Lublin
• Dolno?l?skie Centrum Onkologii — Wroc?aw

South Korea · 4 centers

• Soon Chun Hyang University Cheonan Hospital — Dongnam-gu, Cheonan-si
• Gachon University Gil Medical Center — Namdong-Gu
• Seoul National University Bundang Hospital — Seongnam-si
• Seoul National University Hospital — Seoul

Mexico · 3 centers

• Instituto Nacional De Cancerologia — Distrito Federal
• Centro de Investigacion Clinica de Oaxaca — Oaxaca City
• Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde — Guadalajara

United Kingdom · 3 centers

• Leicester Royal Infirmary — Leicester
• Royal Free Hospital — London
• Christie Hospital Nhs Trust — Manchester

Canada · 2 centers

• CIUSSS du Saguenay Lac-Saint-Jean, Chicoutimi Hospital — Chicoutimi
• McGill University — Montreal

Germany · 2 centers

• Uniklinik RWTH Aachen Klinik für Gynäkologie und Geburtsmedizin — Aachen
• Universitätsklinik Tübingen — Tübingen

Identifiers

NCT: NCT07405801 · CO46274 · 2025-523013-28-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗