A Phase II Study Evaluating the Efficacy and Safety of Inavolisib plus Ribociclib plus Fulvestrant Versus Placebo plus Ribociclib plus Fulvestrant in Patients with Advanced Breast Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Apr 2026 → ongoing

Decision date (initial)

2026-03-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy

To evaluate the efficacy of inavolisib plus ribociclib and fulvestrant compared with placebo plus ribociclib and fulvestrant with respect to investigator-assessed confirmed objective response rate (ORR)

Secondary objectives 3

1. To evaluate the efficacy of inavolisib plus ribociclib and fulvestrant compared with placebo plus ribociclib and fulvestrant with respect to Progression-Free Survival (PFS), overall survival (OS), Investigator-Assessed Duration of Response (DOR), and Investigator-Assessed Clinical Benefit Rate (CBR)
2. To evaluate the safety of inavolisib plus ribociclib and fulvestrant compared with placebo plus ribociclib and fulvestrant
3. To evaluate the tolerability of inavolisib plus ribociclib and fulvestrant compared with placebo plus ribociclib and fulvestrant from the participant's perspective

Conditions and MedDRA coding

Endocrine-Resistant Hormone-Receptor-Positive, HER2-Negative Advanced Breast Cancer with Chromosome 8p Loss and Without PIK3CA Mutation

Regulatory references

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 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
2. 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)
3. Patients 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.
4. 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)
5. Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)

Exclusion criteria 6

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Investigator-Assessed Confirmed ORR

Secondary endpoints 10

1. PFS
2. OS
3. Investigator-assessed DOR
4. Investigator-assessed CBR
5. Incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
6. Change from baseline in targeted vital signs
7. Change from baseline in targeted clinical laboratory test results
8. Presence, frequency of occurrence, severity, and/or degree of interference with daily activities of symptomatic treatment toxicities as assessed through use of the National Cancer Institute (NCI) Patient-Reported Outcome Common Terminology Criteria for Adverse Events (PRO-CTCAE) instrument
9. Proportion of participants reporting each response option at each assessment timepoint by treatment arm for treatment side-effect bother single-item General Population, Question 5 (GP5) from the Functional Assessment of Cancer Therapy-General questionnaire (FACT-G)
10. Change from baseline/worsening in symptomatic treatment toxicities and treatment side-effect bother as assessed through use of the PRO-CTCAE and FACT-G GP5 item, respectively

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 8

Locations

5 EU/EEA countries · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 48 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications