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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

NCT ID: NCT04208178

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-16

Study Completion Date

2026-06-16

Brief Summary

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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.

Detailed Description

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The recruitment for this study was permanently halted as of 07-Dec-2022 with the intent of ending the study early because of the evolving treatment landscape and changing paradigms for HER-2 positive BC therapy. This decision was not triggered by any new or unexpected safety findings. Participants in Part 1 will be allowed to continue study treatment (alpelisib in combination with trastuzumab and pertuzumab) if they are deriving clinical benefit as assessed by the investigator and after discussion with the participant and documentation in the medical record. All participants in Part 2 will be unblinded for knowledge of treatment allocation and continuity treatment planning.Participants in the experimental arm will be allowed to continue alpelisib in combination with trastuzumab and pertuzumab based on investigator's judgement and benefit/risk assessment.Participants in Part 2 who are still receiving study treatment in the control arm with alpelisib matching-placebo will not be allowed cross-over to the experimental arm. These participants will be allowed to continue on trastuzumab and pertuzumab if they are deriving clinical benefit as assessed by the investigator and after discussion with the participant and documentation in the medical record.

Conditions

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Advanced HER2+Breast Cancer

Keywords

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BYL719 alpelisib Advance Breast Cancer maintenance HER2 positive induction PI3K Trastuzumab Pertuzumab

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Part 1 was 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 was initiated, which is the randomized, Phase III part of the study with two treatment arms.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Part 1 was 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. Once the alpelisib dose was confirmed, Part 2 with masking for participant, care provider, investigator and outcome assessor started. Participants in Part 2 are to be unblinded with the implementation of protocol amendment 03.

Study Groups

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Part 1: Alpelisib + Trastuzumab + Pertuzumab

In the Part 1, up to 3 alpelisib dose levels may be sequentially tested in 3 cohorts of subjects:

Cohort A: Alpelisib 300mg + trastuzumab (6mg/kg) + pertuzumab (420 mg) Cohort B: Alpelisib 250 mg+ trastuzumab (6mg/kg) + pertuzumab (420 mg) Cohort C: Alpelisib 200mg + trastuzumab (6mg/kg) + pertuzumab (420 mg)

Group Type EXPERIMENTAL

Alpelisib

Intervention Type DRUG

Alpelisib orally taken - continuous once daily, in a 21-day cycle.

Trastuzumab

Intervention Type DRUG

Trastuzumab 6mg/kg given intravenously - Day 1 of Cycle 1, and on Day 1 of every cycle thereafter (Cycle=21 days)

Pertuzumab

Intervention Type DRUG

Pertuzumab 420 mg given intravenously - Day 1 of Cycle 1, and on Day 1 of every cycle thereafter (Cycle=21 days)

Part 2: Alpelisib + Trastuzumab + Pertuzumab

Trastuzumab (6mg/kg) + pertuzumab (420 mg) in combination with 200mg alpelisib, with potential for intra-participant dose escalation to 250 mg

Group Type EXPERIMENTAL

Alpelisib

Intervention Type DRUG

Alpelisib orally taken - continuous once daily, in a 21-day cycle.

Trastuzumab

Intervention Type DRUG

Trastuzumab 6mg/kg given intravenously - Day 1 of Cycle 1, and on Day 1 of every cycle thereafter (Cycle=21 days)

Pertuzumab

Intervention Type DRUG

Pertuzumab 420 mg given intravenously - Day 1 of Cycle 1, and on Day 1 of every cycle thereafter (Cycle=21 days)

Part 2: Alpelisib matching Placebo + Trastuzumab + Pertuzumab

Trastuzumab (6mg/kg) + pertuzumab (420 mg) in combination with 200 mg alpelisib matching placebo, with potential for intra-participant dose escalation to 250 mg

Group Type PLACEBO_COMPARATOR

Alpelisib matching Placebo

Intervention Type DRUG

Alpelisib matching placebo orally taken - continuous once daily, in a 21-day cycle

Trastuzumab

Intervention Type DRUG

Trastuzumab 6mg/kg given intravenously - Day 1 of Cycle 1, and on Day 1 of every cycle thereafter (Cycle=21 days)

Pertuzumab

Intervention Type DRUG

Pertuzumab 420 mg given intravenously - Day 1 of Cycle 1, and on Day 1 of every cycle thereafter (Cycle=21 days)

Interventions

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Alpelisib

Alpelisib orally taken - continuous once daily, in a 21-day cycle.

Intervention Type DRUG

Alpelisib matching Placebo

Alpelisib matching placebo orally taken - continuous once daily, in a 21-day cycle

Intervention Type DRUG

Trastuzumab

Trastuzumab 6mg/kg given intravenously - Day 1 of Cycle 1, and on Day 1 of every cycle thereafter (Cycle=21 days)

Intervention Type DRUG

Pertuzumab

Pertuzumab 420 mg given intravenously - Day 1 of Cycle 1, and on Day 1 of every cycle thereafter (Cycle=21 days)

Intervention Type DRUG

Other Intervention Names

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BYL719

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Highlands Oncology Group

Fayetteville, Arkansas, United States

Site Status

University of California LA

Los Angeles, California, United States

Site Status

Novartis Investigative Site

Leuven, , Belgium

Site Status

Novartis Investigative Site

Liège, , Belgium

Site Status

Novartis Investigative Site

Changchun, Jilin, China

Site Status

Novartis Investigative Site

Shanghai, , China

Site Status

Novartis Investigative Site

Saint-Cloud, Hauts De Seine, France

Site Status

Novartis Investigative Site

Saint-Herblain, , France

Site Status

Novartis Investigative Site

Florence, FI, Italy

Site Status

Novartis Investigative Site

Kuala Lumpur, , Malaysia

Site Status

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, Spain

Site Status

Countries

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Brazil Canada Czechia Finland Hungary Israel Lebanon Netherlands Poland Singapore Slovakia Sweden Thailand Turkey (Türkiye) United States Belgium China France Italy Malaysia Spain

Other Identifiers

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2024-512050-13-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CBYL719G12301

Identifier Type: -

Identifier Source: org_study_id