BYLieve:alpelisib + fulvestrant or letrozole in advanced breast cancer
Research type
Research Study
Full title
A phase II, multicenter, open-label, two-cohort, noncomparative study to assess the efficacy and safety of alpelisib plus fulvestrant or letrozole in patients with PIK3CA mutant, hormone receptor (HR) positive, HER2-negative advanced breast cancer (aBC), who have progressed on or after CDK 4/6 inhibitor treatment
IRAS ID
230232
Contact name
Nicholas Turner
Contact email
Sponsor organisation
Novartis Pharma AG
Eudract number
2016-004586-67
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Research Summary
This is a phase II, multicenter, open-label, two-cohort, non-comparative study of alpelisib plus endocrine therapy (either fulvestrant or letrozole) in patients with HR+, HER2-negative aBC harboring PIK3CA mutation(s) in the tumor whose disease has progressed on or after CDK 4/6 inhibitor containing treatments. Eligible patients include male and postmenopausal female patients with HR+, HER2-negative aBC harboring PIK3CA mutation(s) whose disease has progressed on or after CDK 4/6 inhibitor combination with endocrine therapy. Eligible patients will be assigned to either cohort A or B based on prior CDKi combination received (with an AI or fulvestrant).
The study will show whether the combination of alpelisib (PI3K inhibitor)with letrozole or fulvestrant is effective in this patient population that is expected to grow significantly with the availability of CDKi combinations in aBC. The study will include approximately 160 men and postmenopausal women with HR+, HER2-negative advanced breast cancer who on or after CDK 4/6 inhibitor combination with endocrine therapy
Patients will undergo molecular pre-screening assessment of PIK3CA mutation status and, is mutated, after having successfully completed screening procedures, will be assigned to one of the cohorts:
Cohort A: Patients who received any CDK 4/6 inhibitor plus any AI as immediate prior treatment, will receive alpelisib + fulvestrant
Cohort B: Patients who received any CDK 4/6 inhibitor plus fulvestrant as immediate prior treatment, will receive alpelisib + letrozole
Patients will receive treatment until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason. Following discontinuation of study treatment for any reason other than disease progression or death, patients will continue to be followed for efficacy. Patients will be followed for disease progression and survival regardless of treatment discontinuation reason (except if consent is withdrawn or patient is lost to follow-up) until the end of study (18 months after last patient first visit (LPFV)).
If alpelisib is not commercially available and reimbursed in a participating country by the time the study is completed (18 months after LPFV), Novartis will have a transition plan in place to ensure that patients have equivalent access without delays in treatmentSummary of results
The English lay summary will be available one year post global LPLV (12/11/2025). It will be available to PIs to share with patients and posted in the public domain on Novartis public website https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.novctrd.com%2F&data=05%7C02%7Cfulham.rec%40hra.nhs.uk%7C16e54ecb9f1a4cb8891308de05811d1a%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638954249275228259%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=qNZ005B7wLtET%2BOObLzV57bmylEvQplyThP06j%2BK0H8%3D&reserved=0“
REC name
London - Fulham Research Ethics Committee
REC reference
17/LO/1468
Date of REC Opinion
10 Nov 2017
REC opinion
Further Information Favourable Opinion