Study of Alpelisib (BYL719) in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy in Patients With HER2-positive Advanced Breast Cancer With a PIK3CA Mutation
Alpelisib: Alpelisib orally taken - continuous once daily, in a 21-day cycle.
Alpelisib matching Placebo: Alpelisib matching placebo orally taken - continuous once daily, in a 21-day cycle
Trastuzumab: Trastuzumab 6mg/kg given intravenously - Day 1 of Cycle 1, and on Day 1 of every cycle thereafter (Cycle=21 days)
Pertuzumab: Pertuzumab 420 mg given intravenously - Day 1 of Cycle 1, and on Day 1 of every cycle thereafter (Cycle=21 days)
Study summary
The purpose of this two part multicenter, randomized, double-blind, placebo-controlled, Phase III study is to evaluate the efficacy and safety of alpelisib compared to alpelisib matching-placebo in combination with trastuzumab and pertuzumab as maintenance treatment of patients with HER2-positive advanced breast cancer whose tumor harbors a PIK3CA mutation following induction therapy with a taxane in combination with trastuzumab and pertuzumab. Part 1 is the open-label, safety run-in part of the study, designed to confirm the recommended phase 3 dose (RP3D) dose of alpelisib in combination with trastuzumab and pertuzumab. Following Part 1, Part 2 will be initiated, which is the randomized, Phase III part of the study.
Eligibility
Sex
ALL
Min age
18 Years
Max age
100 Years
Healthy volunteers
No
Inclusion Criteria:
* Participant has histologically-confirmed HER2-positive breast cancer that is advanced (loco-regionally not amenable to surgery or is metastatic).
* Participant has received pre-study induction therapy with up to and including a maximum of 8 cycles of a taxane (docetaxel, paclitaxel, or nab-paclitaxel), plus trastuzumab and pertuzumab. 4 or 5 cycles of induction therapy are permitted if discontinuation of taxane was due to taxane toxicity. Of note, participants enrolled in Part 1 of this study received 4-6 cycles of pre-study induction therapy.
* Participant has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Participant has adequate bone marrow and organ function
* Applies only to Part 2: Participant has a PIK3CA mutation(s) present in tumor prior to enrollment, locally confirmed per test listed in protocol or as determined by a Novartis designated central laboratory.
Exclusion Criteria:
* Participant with inflammatory breast cancer at screening.
* Participant with evidence of disease progression during the pre-study induction therapy and prior to first dose of alpelisib (or alpelisib/alpelisib matching-placebo for Part 2)
* Participant with an established diagnosis of diabetes mellitus type I or uncontrolled type II based on fasting plasma glucose (FPG) and HbA1c.
* Participant has a known history of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis
* Participant has clinically significant, uncontrolled heart disease and/or recent cardiac events
* Participant has a history of Steven-Johnson Syndrome (SJS), erythema multiforme (EM) or Toxic Epidermal Necrolysis (TEN).
* Participant has currently documented pneumonitis/interstitial lung disease
Other protocol-defined Inclusion/Exclusion may apply.
Primary outcome measure(s)
Part 1: Incidence of dose limiting toxicities (DLTs) for each dose level — 6 weeks Incidence of DLTs during the first 6 weeks of treatment for each dose level associated with administration of alpelisib in combination with trastuzumab and pertuzumab
Part 2: Progression Free Survival (PFS) — Up to approximately 38 months PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is based on local investigator assessment and using RECIST 1.1 criteria
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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