Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant in Participants With HR-postitive (HR+), HER2-negative, Advanced Breast Cancer After Treatment With a CDK4/6 Inhibitor and an Aromatase Inhibitor.

Official Title

EPIK-B5: A Phase III, Randomized, Double-blind, Placebo-controlled Study of Alpelisib in Combination With Fulvestrant for Men and Postmenopausal Women With HR-positive, HER2-negative Advanced Breast Cancer With a PIK3CA Mutation, Who Progressed on or After Aromatase Inhibitor and a CDK4/6 Inhibitor

Summary:

The purpose of this study is to complement Study CBYL719C2301 (SOLAR-1) and obtain more comprehensive data on the efficacy and safety of alpelisib (BYL719) in combination with fulvestrant compared with placebo plus fulvestrant in men or postmenopausal women with HR-positive, HER2-negative advanced breast cancer with a PIK3CA mutation who progressed or relapsed on or after treatment with an AI plus a CDK4/6 inhibitor.

Trial Description

Primary Outcome:

  • Progression-free survival (PFS) based on BIRC assessments and using RECIST v1.1 criteria
Secondary Outcome:
  • Overall survival (OS)
  • Overall response rate (ORR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria
  • Clinical benefit rate (CBR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria
  • Duration of response (DOR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria
  • Time to response (TTR) based on BIRC assessments and using RECIST v1.1 criteria
  • PFS based on BIRC assessment and using RECIST v1.1 criteria for participants by PIK3CA mutation status
  • Time to definitive deterioration of Eastern Cooperative Oncology Group (ECOG) performance status (PS) from baseline
  • Time to definitive (10%) deterioration in the global health status/Quality of Life (QoL) and symptom scale scores of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30)
  • Change from baseline in global health status/QoL and symptom scale scores of the EORTC QLQ-C30
  • Time from randomization to objective tumour progression on next line treatment or death from any cause (PFS2)
This is a Phase III, randomized, double-blind, placebo-controlled, international, multi-centre trial. Approximately 234 men and postmenopausal women will be randomized to either alpelisib plus fulvestrant or alpelisib-matching placebo plus fulvestrant. Randomization will follow a 1:1 randomization ratio and be stratified by presence of lung and/or liver metastases (yes vs. no) and setting at last prior CDK4/6 inhibitor therapy (adjuvant vs metastatic). Study treatment with alpelisib plus fulvestrant or alpelisib-matching placebo plus fulvestrant will be initiated on Cycle 1 Day 1, and will continue until disease progression per RECIST v1.1 as per BIRC assessment, start of new antineoplastic therapy, death, lost to follow-up, or withdrawal of consent. A cycle is defined as 28 days. Participants randomized to the alpelisib-matching placebo plus fulvestrant arm who have disease progression per RECIST v1.1 as assessed by BIRC will have the option to crossover to be treated with alpelisib plus fulvestrant. Unblinding a single participant at a site will be permitted after disease progression confirmed by BIRC after discussion with the Novartis team to determine eligibility for cross-over to treatment with alpelisib plus fulvestrant.

View this trial on ClinicalTrials.gov

Interested in this trial?

Print this page and take it to your doctor to discuss your eligibilty and treatment options. Only your doctor can refer you to a clinical trial.

Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society