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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

Trial Status: Active

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.

Inclusion Criteria

  • Subject has histologically-confirmed HER2-positive breast cancer that is advanced (loco-regionally not amenable to surgery or is metastatic).
  • Subject has received pre-study induction therapy with up to and including 6 cycles of a taxane (docetaxel, paclitaxel, or nab-paclitaxel), plus trastuzumab and pertuzumab. A minimum of 4 cycles of taxane is permitted if discontinuation was due to toxicity
  • Subject has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Subject has adequate bone marrow and organ function
  • Applies only to Part 2: Subject has a PIK3CA mutation(s) present in tumor tissue prior to enrollment, as determined by a Novartis designated central laboratory.

Exclusion Criteria

  • Subject with inflammatory breast cancer at screening.
  • Subject 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)
  • Subject with an established diagnosis of diabetes mellitus type I or uncontrolled type II based on fasting plasma glucose (FPG) and HbA1c.
  • Subject has a known history of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis
  • Subject has clinically significant, uncontrolled heart disease and/or recent cardiac events
  • Subject has a history of Steven-Johnson Syndrome (SJS), erythema multiforme (EM) or Toxic Epidermal Necrolysis (TEN).
  • Subject has currently documented pneumonitis/interstitial lung disease


City of Hope Comprehensive Cancer Center
Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Contact: Virginia Del Casal
Phone: 310-633-8400
San Francisco
University of California San Francisco
Contact: UCSF Clinical Trials
Phone: 877-827-3222


Northwestern University


Fred Hutch / University of Washington Cancer Consortium


University of Wisconsin Hospital and Clinics

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Novartis Pharmaceuticals Corporation

  • Primary ID CBYL719G12301
  • Secondary IDs NCI-2020-02351, 2019-002741-37
  • ID NCT04208178