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

• Status: Recruiting
• Trial end date: 2031-02-18
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this two parts 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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: Pertuzumab; Trastuzumab

Criteria

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 6 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.

• 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 tissue prior to enrollment, 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.