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

EPIK-B2: A Two Part, Phase III, Multicenter, Randomized (1:1), Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Alpelisib (BYL719) in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy in Patients With HER2-positive Advanced Breast Cancer With a PIK3CA Mutation

ClinicalTrials.gov Identifier: NCT04208178

Novartis Reference Number: CBYL719G12301

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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.

Condition 
Advanced HER2+Breast Cancer
Phase 
Phase 3
Overall status 
Recruiting
Enrollment count 
588 participants
Start date 
Jul 16, 2020
Completion date 
Oct 15, 2030
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
Alpelisib
Alpelisib - continuous once daily, in a 21-day cycle
Drug
Alpelisib matching Placebo
Alpelisib matching placebo: continuous once daily, in a 21-day cycle
Drug
Trastuzumab
Trastuzumab - Day 1 of Cycle 1, and on Day 1 (+/- 3 days) of every cycle thereafter
Drug
Pertuzumab
Pertuzumab - Day 1 of Cycle 1, and on Day 1 (+/- 3 days) of every cycle thereafter

Eligibility Criteria

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

Other protocol-defined Inclusion/Exclusion may apply.

Study Locations

United States
Highlands Oncology Group
Recruiting
Fayetteville, 72703
Arkansas
United States
Lurie Children's Hospital of Chicago Drug Shipment
Recruiting
Chicago, 60611
Illinois
United States
Belgium
Novartis Investigative Site
Recruiting
Leuven, 3000
-
Belgium
Novartis Investigative Site
Recruiting
Liege, 4000
-
Belgium
France
Novartis Investigative Site
Recruiting
Saint-Cloud, 92210
Hauts De Seine
France
Novartis Investigative Site
Recruiting
Saint-Herblain Cédex, 44805
-
France

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Email: 

Have a question?

Call 1-999-669-6682 or email [email protected]