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

NCT04251533 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: CBYL719H123012024-511931-87-002019-002637-11
• Study Type: interventional
• Target: 137
• Locations: 28 countries
• Sites: 75

Brief Summary

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)

Conditions

Triple Negative Breast Neoplasms

Keywords

Triple Negative Breast Cancer; alpelisib; BYL719; nab-paclitaxel; PIK3CA mutation; PTEN loss

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (12)

• Overall Survival in Study Part A

  Up to 66 months

• Overall Response Rate (ORR) With Confirmed Response in Study Part A

  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

  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

  Up to 6 months

• Time to Response (TTR) in Study Part A

  Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months

Study Arms (3)

Part A: alpelisib + nab-paclitaxel

EXPERIMENTAL

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; Drug: nab-paclitaxel

Part A: placebo + nab-paclitaxel

PLACEBO COMPARATOR

Participants received placebo + nab-paclitaxel 100 mg/m\^2 IV on Days 1, 8, and 15 of each 28-day cycle.

Drug: placebo; Drug: nab-paclitaxel

Part B1: alpelisib + nab-paclitaxel

EXPERIMENTAL

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; Drug: nab-paclitaxel

Interventions

alpelisib DRUG

300 mg orally, once per day (QD), tablets

Also known as: BYL719

Part A: alpelisib + nab-paclitaxel; Part B1: alpelisib + nab-paclitaxel

placebo DRUG

300 mg orally, once per day (QD), tablets

Also known as: alpelisib-matching placebo

Part A: placebo + nab-paclitaxel

nab-paclitaxel DRUG

100 mg/m\^2 IV infusion, once per day (QD)

Also known as: abraxane

Part A: alpelisib + nab-paclitaxel; Part A: placebo + nab-paclitaxel; Part B1: alpelisib + nab-paclitaxel

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (78)

University of California LA

Los Angeles, California, 90095, United States

Location

Hematology and Oncology Clinic

Baton Rouge, Louisiana, 70809, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Park Nicollet Institute

Saint Louis Park, Minnesota, 55416, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

Novartis Investigative Site

Rosario, Santa Fe Province, S2000KZE, Argentina

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Novartis Investigative Site

CABA, C1113AAE, Argentina

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Novartis Investigative Site

Melbourne, Victoria, 3000, Australia

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Novartis Investigative Site

Nedlands, Western Australia, 6009, Australia

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Innsbruck, Tyrol, 6020, Austria

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Leoben, A 8700, Austria

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Barretos, São Paulo, 14784 400, Brazil

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São Paulo, São Paulo, 01317-002, Brazil

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São Paulo, São Paulo, 04014-002, Brazil

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Plovdiv, 4004, Bulgaria

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Hefei, Anhui, 230001, China

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Shijiazhuang, Hebei, 050011, China

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Changsha, Hunan, 410013, China

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Nanjing, Jiangsu, 210029, China

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Nanchang, Jiangxi, 330009, China

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Changchun, Jilin, 130021, China

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Shengyang, Liaoning, 110042, China

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Shenyang, Liaoning, 110011, China

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Chengdu, Sichuan, 610041, China

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Hangzhou, Zhejiang, 310016, China

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Dalian, 116000, China

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Shanghai, 200025, China

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Tianjin, 300480, China

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Bogotá, 110221, Colombia

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Zagreb, 10000, Croatia

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Saint-Cloud, Hauts De Seine, 92210, France

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Angers, 49055, France

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Saint-Herblain, 44805, France

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Villejuif, 94800, France

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Dresden, Saxony, 01307, Germany

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Leipzig, Saxony, 04103, Germany

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Essen, 45136, Germany

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Budapest, 1134, Hungary

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Faridabad, Haryana, 121 001, India

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Mumbai, Maharashtra, 400056, India

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Vellore, Tamil Nadu, 632 004, India

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Hyderabad, Telangana, 500034, India

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Tel Aviv, 6423906, Israel

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Meldola, FC, 47014, Italy

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Roma, RM, 00128, Italy

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Naples, 80131, Italy

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Petaling Jaya, Selangor, 46050, Malaysia

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Kuala Lumpur, 59100, Malaysia

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Monterrey, Nuevo León, 64460, Mexico

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Oslo, NO-0407, Norway

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Trujillo, La Libertad, 13011, Peru

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Gdynia, 81 519, Poland

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Opole, 45-061, Poland

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Poznan, 61 485, Poland

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Arkhangelsk, 163045, Russia

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Chelyabinsk, 454048, Russia

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Moscow, 117997, Russia

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Moscow, 123056, Russia

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Saint Petersburg, 196603, Russia

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Bratislava, 812 50, Slovakia

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Bratislava, 83310, Slovakia

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Košice, 041 91, Slovakia

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Ljubljana, 1000, Slovenia

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Port Elizabeth, Western Cape, 6045, South Africa

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Johannesburg, 2196, South Africa

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Seoul, 03080, South Korea

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Seoul, 05505, South Korea

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Seoul, 06351, South Korea

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Palma, Balearic Islands, 07120, Spain

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Badajoz, Extremadura, 06080, Spain

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Alicante, 03010, Spain

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Lausanne, 1011, Switzerland

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Taipei, 10002, Taiwan

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Novartis Investigative Site

Taipei, 10449, Taiwan

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Istanbul, Fatih, 34098, Turkey (Türkiye)

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Istanbul, Kadikoy, 34722, Turkey (Türkiye)

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Nottingham, NG5 1PB, United Kingdom

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Oxford, OX3 7LE, United Kingdom

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MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Alpelisib; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2020
• First Posted: February 5, 2020
• Study Start: June 8, 2020
• Primary Completion: May 31, 2023
• Study Completion: February 5, 2026
• Last Updated: May 11, 2026
• Results First Posted: July 31, 2024

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (5); CN (13); MY (2); ZA (2); TU (2); PL (3); KR (3); IL (1); PE (1); NO (1); RU (5); CO (1); CR (1); SL (3); GB (2); ME (1); CH (1); ES (3); BU (1); DE (3); TW (2); IT (3); AR (2); IN (4); BR (3); FR (4); HU (1); AU (2)