Study Assessing the Efficacy and Safety of Alpelisib + Nab-paclitaxel in Subjects With Advanced TNBC Who Carry Either a PIK3CA Mutation or Have PTEN Loss (EPIK-B3)

A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Alpelisib (BYL719) in Combination With Nab-paclitaxel in Patients With Advanced Triple Negative Breast Cancer With Either Phosphoinositide-3-kinase Catalytic Subunit Alpha (PIK3CA) Mutation or Phosphatase and Tensin Homolog Protein (PTEN) Loss Without PIK3CA Mutation

The purpose of this study was to determine whether treatment with alpelisib in combination with nab-paclitaxel is safe and effective in subjects with advanced triple negative breast cancer (aTNBC) who carry either a PIK3CA mutation (Study Part A) or have PTEN loss (Study Part B1) or PTEN loss without PIK3CA mutation (Study Part B2)

Study Overview

• Status: Terminated
• Conditions: Triple Negative Breast Neoplasms
• Intervention / Treatment: Drug: alpelisib; Drug: nab-paclitaxel; Drug: placebo

Detailed Description

The recruitment of Part A was halted on 11-Nov-2022 due to slow recruitment. Since Part B1 did not meet its primary objective for confirmed overall response rate, the Part B2 was not initiated, and the recruitment was halted for the entire study.

Upon confirming either PIK3CA mutation and/or PTEN loss status, advanced TNBC participants meeting all other eligibility criteria were assigned to either Part A (PIK3CA mutation regardless of PTEN loss) or Part B1 (PTEN loss with PIK3CA unknown or non-mutant).

In Part A, participants were randomized a 1:1 to receive either:

• alpelisib 300 mg daily orally + nab-paclitaxel 100 mg/m^2 intravenously (IV) on Days 1, 8, and 15 of each 28-day cycle or
• placebo + nab-paclitaxel 100 mg/m^2 IV on Days 1, 8, and 15 of each 28-day cycle.

In Part B1, participants received alpelisib 300 mg daily orally + nab-paclitaxel 100 mg/m^2 IV on Days 1, 8, and 15 of each 28-day cycle.

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • CABA, Argentina, C1113AAE
    • Novartis Investigative Site
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2000KZE
      • Novartis Investigative Site
• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Novartis Investigative Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Novartis Investigative Site
• Austria
  • Leoben, Austria, A 8700
    • Novartis Investigative Site
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Novartis Investigative Site
• Brazil
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784 400
      • Novartis Investigative Site
    • São Paulo, São Paulo, Brazil, 04014-002
      • Novartis Investigative Site
    • São Paulo, São Paulo, Brazil, 01317-002
      • Novartis Investigative Site
• Bulgaria
  • Plovdiv, Bulgaria, 4004
    • Novartis Investigative Site
• China
  • Dalian, China, 116000
    • Novartis Investigative Site
  • Shanghai, China, 200025
    • Novartis Investigative Site
  • Tianjin, China, 300480
    • Novartis Investigative Site
  • Anhui
    • Hefei, Anhui, China, 230001
      • Novartis Investigative Site
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • Novartis Investigative Site
  • Hunan
    • Changsha, Hunan, China, 410013
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Novartis Investigative Site
  • Jiangxi
    • Nanchang, Jiangxi, China, 330009
      • Novartis Investigative Site
  • Jilin
    • Changchun, Jilin, China, 130021
      • Novartis Investigative Site
  • Liaoning
    • Shengyang, Liaoning, China, 110042
      • Novartis Investigative Site
    • Shenyang, Liaoning, China, 110011
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Novartis Investigative Site
• Colombia
  • Bogotá, Colombia, 110221
    • Novartis Investigative Site
• Croatia
  • Zagreb, Croatia, 10000
    • Novartis Investigative Site
• France
  • Angers, France, 49055
    • Novartis Investigative Site
  • Saint-Herblain, France, 44805
    • Novartis Investigative Site
  • Villejuif, France, 94800
    • Novartis Investigative Site
  • Hauts De Seine
    • Saint-Cloud, Hauts De Seine, France, 92210
      • Novartis Investigative Site
• Germany
  • Essen, Germany, 45136
    • Novartis Investigative Site
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Novartis Investigative Site
    • Leipzig, Saxony, Germany, 04103
      • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1134
    • Novartis Investigative Site
• India
  • Haryana
    • Faridabad, Haryana, India, 121 001
      • Novartis Investigative Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400056
      • Novartis Investigative Site
  • Tamil Nadu
    • Vellore, Tamil Nadu, India, 632 004
      • Novartis Investigative Site
  • Telangana
    • Hyderabad, Telangana, India, 500034
      • Novartis Investigative Site
• Israel
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • Naples, Italy, 80131
    • Novartis Investigative Site
  • FC
    • Meldola, FC, Italy, 47014
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00128
      • Novartis Investigative Site
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Novartis Investigative Site
  • Selangor
    • Petaling Jaya, Selangor, Malaysia, 46050
      • Novartis Investigative Site
• Mexico
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Novartis Investigative Site
• Norway
  • Oslo, Norway, NO-0407
    • Novartis Investigative Site
• Peru
  • La Libertad
    • Trujillo, La Libertad, Peru, 13011
      • Novartis Investigative Site
• Poland
  • Gdynia, Poland, 81 519
    • Novartis Investigative Site
  • Opole, Poland, 45-061
    • Novartis Investigative Site
  • Poznan, Poland, 61 485
    • Novartis Investigative Site
• Russia
  • Arkhangelsk, Russia, 163045
    • Novartis Investigative Site
  • Chelyabinsk, Russia, 454048
    • Novartis Investigative Site
  • Moscow, Russia, 117997
    • Novartis Investigative Site
  • Moscow, Russia, 123056
    • Novartis Investigative Site
  • Saint Petersburg, Russia, 196603
    • Novartis Investigative Site
• Slovakia
  • Bratislava, Slovakia, 812 50
    • Novartis Investigative Site
  • Bratislava, Slovakia, 83310
    • Novartis Investigative Site
  • Košice, Slovakia, 041 91
    • Novartis Investigative Site
• Slovenia
  • Ljubljana, Slovenia, 1000
    • Novartis Investigative Site
• South Africa
  • Johannesburg, South Africa, 2196
    • Novartis Investigative Site
  • Western Cape
    • Port Elizabeth, Western Cape, South Africa, 6045
      • Novartis Investigative Site
• South Korea
  • Seoul, South Korea, 03080
    • Novartis Investigative Site
  • Seoul, South Korea, 05505
    • Novartis Investigative Site
  • Seoul, South Korea, 06351
    • Novartis Investigative Site
• Spain
  • Alicante, Spain, 03010
    • Novartis Investigative Site
  • Balearic Islands
    • Palma, Balearic Islands, Spain, 07120
      • Novartis Investigative Site
  • Extremadura
    • Badajoz, Extremadura, Spain, 06080
      • Novartis Investigative Site
• Switzerland
  • Lausanne, Switzerland, 1011
    • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taipei, Taiwan, 10449
    • Novartis Investigative Site
• Turkey (Türkiye)
  • Fatih
    • Istanbul, Fatih, Turkey (Türkiye), 34098
      • Novartis Investigative Site
  • Kadikoy
    • Istanbul, Kadikoy, Turkey (Türkiye), 34722
      • Novartis Investigative Site
• United Kingdom
  • Nottingham, United Kingdom, NG5 1PB
    • Novartis Investigative Site
  • Oxford, United Kingdom, OX3 7LE
    • Novartis Investigative Site
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California LA
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Hematology and Oncology Clinic
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI Oncology Partners

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant has histologically confirmed diagnosis of advanced (loco-regionally recurrent and not amenable to curative therapy), or metastatic (stage IV) TNBC
• Participant has either a measurable disease per RECIST 1.1 criteria or, if no measurable disease is present, then at least one predominantly lytic bone lesion or mixed lytic-blastic bone lesion with identifiable soft tissue component (that can be evaluated by CT/MRI) must be present. Part B1: Participants must have measurable disease
• Participant has adequate tumor tissue to identify the PIK3CA mutation status (either carrying a mutation or without a mutation) and the PTEN loss status; both of which will determine whether the subject can be allocated to Part A - PIK3CA mutation regardless of PTEN status; or to Part B1 - PTEN loss or to Part B2 - PTEN loss without a PIK3CA mutation
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Participant has received no more than one line of therapy for metastatic disease
• Participant has adequate bone marrow and organ function

Exclusion Criteria:

• Participant has received prior treatment with any PI3K, mTOR or AKT inhibitor
• Participant has a known hypersensitivity to alpelisib, nab-paclitaxel or to any of their excipients
• Participant has not recovered from all toxicities related to prior anticancer therapies to NCI CTCAE version 4.03 Grade ≤1; with the exception of alopecia
• Participant has central nervous system (CNS) involvement which was not previously treated and/or was newly detected at screening
• Participant with an established diagnosis of diabetes mellitus type I or uncontrolled type II based on Fasting Plasma Glucose and HbA1c
• Participant has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) based on investigator discretion
• Participant has a history of acute pancreatitis within 1 year prior to screening or past medical history of chronic pancreatitis
• Participant has currently documented pneumonitis/interstitial lung disease
• Participant has a history of severe cutaneous reactions, such as Steven-Johnson Syndrome (SJS), erythema multiforme (EM),Toxic Epidermal Necrolysis (TEN) or Drug Reaction with Eosinophilia and Systemic Syndrome (DRESS)
• Participant with unresolved osteonecrosis of the jaw

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: alpelisib + nab-paclitaxel; Participants received alpelisib 300 mg orally + nab-paclitaxel 100 mg/m^2 intravenously (IV) on Days 1, 8, and 15 of each 28-day cycle	Drug: alpelisib; 300 mg orally, once per day (QD), tablets; Other Names: BYL719; Drug: nab-paclitaxel; 100 mg/m^2 IV infusion, once per day (QD); Other Names: abraxane
Placebo Comparator: Part A: placebo + nab-paclitaxel; Participants received placebo + nab-paclitaxel 100 mg/m^2 IV on Days 1, 8, and 15 of each 28-day cycle.	Drug: nab-paclitaxel; 100 mg/m^2 IV infusion, once per day (QD); Other Names: abraxane; Drug: placebo; 300 mg orally, once per day (QD), tablets; Other Names: alpelisib-matching placebo
Experimental: Part B1: alpelisib + nab-paclitaxel; Participants received alpelisib 300 mg orally + nab-paclitaxel 100 mg/m^2 IV on Days 1, 8, and 15 of each 28-day cycle.	Drug: alpelisib; 300 mg orally, once per day (QD), tablets; Other Names: BYL719; Drug: nab-paclitaxel; 100 mg/m^2 IV infusion, once per day (QD); Other Names: abraxane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) Per Investigator Assessment in Study Part A	PFS was defined as time from the date of randomization to the date of the first documented progressive disease (PD) or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1. PD=At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm^2. PFS was censored at the date of the last adequate tumor assessment, if no PFS event was observed prior to the analysis cut-off date.	Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Overall Response Rate (ORR) Based on Local Radiology Assessments in Participants With Measurable Disease at Baseline in Study Part B1	ORR was defined as the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1. BOR was defined as the best response recorded from the start of the study treatment until progressive disease (PD)/recurrence. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; PD= At least a 20% increase in the sum of diameters of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, the sum must also demonstrate an absolute increase of at least 5 mm.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival in Study Part A	Overall survival is defined as the time from date of randomization to date of death due to any cause.	Up to 66 months
Overall Response Rate (ORR) With Confirmed Response in Study Part A	ORR with confirmed response was the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), as per local review and according to RECIST 1.1. BOR was defined as the best response recorded from the start of the study treatment until progressive disease (PD)/recurrence. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; PD= At least a 20% increase in the sum of diameters of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, the sum must also demonstrate an absolute increase of at least 5 mm.	Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Clinical Benefit Rate (CBR) With Confirmed Response in Study Part A	Clinical benefit rate (CBR) was defined as the percentage of participants with a best overall response of complete response (CR), or partial response (PR) or an overall lesion response of stable disease (SD), lasting as per local review, for a duration of at least 24 weeks. CR, PR and SD are defined according to RECIST 1.1 based on investigator's assessment. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.	Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Clinical Benefit Rate (CBR) With Confirmed Response in Study Part B1	Clinical benefit rate (CBR) was defined as the percentage of participants with a best overall response of complete response (CR), or partial response (PR) or an overall lesion response of stable disease (SD), lasting as per local review, for a duration of at least 24 weeks. CR, PR and SD are defined according to RECIST 1.1 based on investigator's assessment. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.	Up to 6 months
Time to Response (TTR) in Study Part A	Time to response (TTR) was defined as the time from the date of randomization/enrolment to the first documented response of either complete response (CR) or partial response (PR), which must be subsequently confirmed (although date of initial response is used, not date of confirmation). CR and PR were based on tumor response data as per local review and according to RECIST 1.1. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.	Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Time to Response (TTR) in Study Part B1	Time to response (TTR) was defined as the time from the date of randomization/enrolment to the first documented response of either complete response (CR) or partial response (PR), which must be subsequently confirmed (although date of initial response was used, not date of confirmation). CR and PR were based on tumor response data as per local review and according to RECIST 1.1. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.	Up to 6 months
Duration of Response (DOR) With Confirmed Response in Study Part A	Duration of response (DOR) with confirmed response only applied to participants whose best overall response (BOR) was confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date was the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date was defined as the date of the first documented progressive disease (PD) or death due to underlying cancer. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.	Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Duration of Response (DOR) With Confirmed Response in Study Part B1	Duration of response (DOR) with confirmed response only applied to participants whose best overall response (BOR) was confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date was the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date was defined as the date of the first documented progressive disease (PD) or death due to underlying cancer. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.	Up to approximately 20 months
Overall Survival in Study Part B1	Overall survival for Part B1 was defined as the number of participants who were alive at the end of the post-treatment period.	Up to approximately 26 months.
Progression-free Survival (PFS) Per Investigator Assessment in Study Part B1	PFS was defined as time from the date of enrolment to the date of the first documented progressive disease (PD) or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1. PD=At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm^2. PFS was censored at the date of the last adequate tumor assessment, if no PFS event was observed prior to the analysis cut-off date.	Up to 6 months
PFS Based on Local Radiology Assessments Using RECIST 1.1 Criteria for Participants by PIK3CA Mutation Status Measured in Baseline Circulating Tumor Deoxyribonucleic Acid (ctDNA) in Study Part A	PFS in participants with PIK3CA mutation as measured in ctDNA. PFS was defined as time from the date of randomization to the date of the first documented progression or death due to any cause.	Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Post-Hoc: All Collected Deaths	On-treatment deaths due to any cause were collected from first dose of study medication to 30 days after the last dose of study treatment. Post-treatment survival follow-up deaths were collected from Day 31 after last dose of study medication to the data cut-off date.	On-treatment deaths: Up to approximately 28 months (Part A) or approximately 17 months (Part B1). Post-treatment survival follow-up deaths: Up to approximately 7 additional months (Part A) or approximately 9 additional months (Part B1).

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2020
• Primary Completion (Actual): May 31, 2023
• Study Completion (Actual): February 5, 2026

Study Registration Dates

• First Submitted: January 30, 2020
• First Submitted That Met QC Criteria: January 30, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: BYL719; Triple Negative Breast Cancer; nab-paclitaxel; PTEN loss; PIK3CA mutation; alpelisib
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Skin and Connective Tissue Diseases; Triple Negative Breast Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Albumins; Paclitaxel; Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel; Alpelisib
• Other Study ID Numbers: CBYL719H12301; 2019-002637-11 (EudraCT Number); 2024-511931-87-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No