Inavolisib plus fulvestrant for PIK3CA‑mutated HR‑positive, HER2‑negative advanced breast cancer after CDK4/6 inhibitors
A Phase II, Randomized, Open-Label Study Evaluating Two Inavolisib Dose Levels in Combination With Fulvestrant in Participants With PIK3CA-Mutated, HR-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer
This tests whether adding inavolisib to fulvestrant helps people with PIK3CA‑mutated, hormone receptor–positive, HER2‑negative locally advanced or metastatic breast cancer whose disease progressed after CDK4/6 inhibitor therapy.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 80 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Hoffmann-La Roche Industry-sponsored |
| Drugs / interventions | chemotherapy |
| Locations | 19 sites (Los Angeles, California and 18 other locations) |
| Trial ID | NCT07368998 on ClinicalTrials.gov |
What this trial studies
This phase 2 interventional study enrolls participants with ER‑positive, HER2‑negative locally advanced or metastatic breast cancer who have a confirmed PIK3CA mutation and progression after CDK4/6 inhibitor plus endocrine therapy. Eligible participants receive inavolisib in combination with fulvestrant and are followed with tumor assessments per RECIST v1.1 and routine safety monitoring. The trial requires measurable or evaluable disease, life expectancy greater than six months, and collection of patient‑reported outcomes. Key outcomes include anti‑tumor activity, progression‑free intervals, and adverse event profiles.
Who should consider this trial
Good fit: Adults with ER+/HER2‑ locally advanced or metastatic breast cancer who have at least one qualifying PIK3CA mutation, progressed on a CDK4/6 inhibitor, and for whom endocrine‑based therapy is still appropriate are the intended participants.
Not a fit: Patients without a PIK3CA mutation, with HER2‑positive or metaplastic tumors, or those who require immediate cytotoxic chemotherapy are unlikely to benefit from this combination.
Why it matters
Potential benefit: If successful, the combination could delay disease progression and provide a new targeted option for PIK3CA‑mutated, HR‑positive patients after CDK4/6 inhibitor therapy.
How similar studies have performed: Other PI3K‑targeting agents combined with endocrine therapy have shown benefit in PIK3CA‑mutant HR‑positive breast cancer, although safety and patient selection have been key considerations.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Documented ER +/ HER2- tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines * Disease progression after or during treatment with a combination of CDK4/6i and endocrine therapy: \<= 1 prior lines of systemic therapy in the locally advanced (recurrent or progressed) or metastatic setting * Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) * Participants for whom endocrine-based therapy is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study, as per national or local treatment guidelines * Confirmation of biomarker eligibility: presence of \>= 1 study-eligible PIK3CA mutation * Life expectancy of \> 6 months * Ability, in the investigator's judgment, and willingness to comply with all study -related procedures, including completion of patient-reported outcomes Exclusion Criteria: * Metaplastic breast cancer * Prior treatment with chemotherapy in the recurrent locally advanced/metastatic setting * Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes * Prior treatment with PI3K/Akt/mTOR inhibitors in the recurrent locally advanced/metastatic setting * Requirement for daily supplemental oxygen * Symptomatic active lung disease, including pneumonitis
Where this trial is running
Los Angeles, California and 18 other locations
- Los Angeles Cancer Network — Los Angeles, California, United States (Recruiting)
- Astera Cancer Care East Brunswick — East Brunswick, New Jersey, United States (Recruiting)
- Centro Oncologico Korben — Ciudad Autonoma Buenos Aires, Argentina (Recruiting)
- Hospital Provincial del Centenario — Rosario, Argentina (Recruiting)
- Bendigo Cancer Centre — Bendigo, Victoria, Australia (Recruiting)
- Cliniques Universitaires St-Luc — Brussels, Belgium (Recruiting)
- Jessa Zkh (Campus Virga Jesse) — Hasselt, Belgium (Recruiting)
- UZ Leuven Gasthuisberg — Leuven, Belgium (Recruiting)
- Hospital Universitari Vall d'Hebron;Oncology — Barcelona, Spain (Recruiting)
- Hospital Universitario San Cecilio — Granada, Spain (Recruiting)
- Hospital Universitario 12 De Octubre — Madrid, Spain (Recruiting)
- Hospital Clinico Universitario de Valencia — Valencia, Spain (Recruiting)
- Bagcilar Medipol Mega Universitesi Hastanesi — Bağcılar, Istanbul, Turkey (Türkiye) (Recruiting)
- Adana Baskent University Hospital — Adana, Turkey (Türkiye) (Recruiting)
- Memorial Ankara Hastanesi — Ankara, Turkey (Türkiye) (Recruiting)
- Medical Park Seyhan Hospital — Seyhan, Turkey (Türkiye) (Recruiting)
- Blackpool Victoria Hospital — Blackpool, United Kingdom (Recruiting)
- Princess Alexandra Hospital — Harlow, United Kingdom (Recruiting)
- Mount Vernon Cancer Centre — Northwood, Middlesex, United Kingdom (Recruiting)
Study contacts
- Study coordinator: Reference Study ID Number: WO46063 https://forpatients.roche.com/
- Email: global-roche-genentech-trials@gene.com
- Phone: 888-662-6728
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.