Triple Negative Breast NeoplasmsPhase 3EPIK-B3NCT04251533
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
A Phase 3 study testing alpelisib and nab-paclitaxel in people with Triple Negative Breast Neoplasms, run by Novartis Pharmaceuticals at 78 sites in 30 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Triple Negative Breast Neoplasms
- What is being tested?
- alpelisib and nab-paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 137 participants
- Where
- 78 sitesin 30 countries
- Study dates
- 8 Jun 2020to 5 Feb 2026
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
78 sites in 30 countries.
78 sites in 30 countries
China13 sites
Novartis Investigative Site
Changchun, Jilin, 130021
Novartis Investigative Site
Changsha, Hunan, 410013
Novartis Investigative Site
Chengdu, Sichuan, 610041
Novartis Investigative Site
Dalian, 116000
Novartis Investigative Site
Hangzhou, Zhejiang, 310016
Novartis Investigative Site
Hefei, Anhui, 230001
Novartis Investigative Site
Nanchang, Jiangxi, 330009
Novartis Investigative Site
Nanjing, Jiangsu, 210029
Novartis Investigative Site
Shanghai, 200025
Novartis Investigative Site
Shengyang, Liaoning, 110042
Novartis Investigative Site
Shenyang, Liaoning, 110011
Novartis Investigative Site
Shijiazhuang, Hebei, 050011
Novartis Investigative Site
Tianjin, 300480
United States5 sites
Hematology and Oncology Clinic
Baton Rouge, Louisiana, 70809
University of California LA
Los Angeles, California, 90095
SCRI Oncology Partners
Nashville, Tennessee, 37203
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Park Nicollet Institute
Saint Louis Park, Minnesota, 55416
Russia5 sites
Novartis Investigative Site
Arkhangelsk, 163045
Novartis Investigative Site
Chelyabinsk, 454048
Novartis Investigative Site
Moscow, 117997
Novartis Investigative Site
Moscow, 123056
Novartis Investigative Site
Saint Petersburg, 196603
France4 sites
Novartis Investigative Site
Angers, 49055
Novartis Investigative Site
Saint-Cloud, Hauts De Seine, 92210
Novartis Investigative Site
Saint-Herblain, 44805
Novartis Investigative Site
Villejuif, 94800
India4 sites
Novartis Investigative Site
Faridabad, Haryana, 121001
Novartis Investigative Site
Hyderabad, Telangana, 500034
Novartis Investigative Site
Mumbai, Maharashtra, 400056
Novartis Investigative Site
Vellore, Tamil Nadu, 632004
Brazil3 sites
Novartis Investigative Site
Barretos, São Paulo, 14784-400
Novartis Investigative Site
São Paulo, São Paulo, 01317-002
Novartis Investigative Site
São Paulo, São Paulo, 04014-002
Germany3 sites
Novartis Investigative Site
Dresden, Saxony, 01307
Novartis Investigative Site
Essen, 45136
Novartis Investigative Site
Leipzig, Saxony, 04103
Italy3 sites
Novartis Investigative Site
Meldola, FC, 47014
Novartis Investigative Site
Naples, 80131
Novartis Investigative Site
Roma, RM, 00128
Poland3 sites
Novartis Investigative Site
Gdynia, 81-519
Novartis Investigative Site
Opole, 45-061
Novartis Investigative Site
Poznan, 61-485
Slovakia3 sites
Novartis Investigative Site
Bratislava, 812 50
Novartis Investigative Site
Bratislava, 83310
Novartis Investigative Site
Košice, 041 91
South Korea3 sites
Novartis Investigative Site
Seoul, 03080
Novartis Investigative Site
Seoul, 05505
Novartis Investigative Site
Seoul, 06351
Spain3 sites
Novartis Investigative Site
Alicante, 03010
Novartis Investigative Site
Badajoz, Extremadura, 06080
Novartis Investigative Site
Palma, Balearic Islands, 07120
Argentina2 sites
Novartis Investigative Site
CABA, C1113AAE
Novartis Investigative Site
Rosario, Santa Fe Province, S2000KZE
Australia2 sites
Novartis Investigative Site
Melbourne, Victoria, 3000
Novartis Investigative Site
Nedlands, Western Australia, 6009
Austria2 sites
Novartis Investigative Site
Innsbruck, Tyrol, 6020
Novartis Investigative Site
Leoben, 8700
Malaysia2 sites
Novartis Investigative Site
Kuala Lumpur, 59100
Novartis Investigative Site
Petaling Jaya, Selangor, 46050
South Africa2 sites
Novartis Investigative Site
Johannesburg, 2196
Novartis Investigative Site
Port Elizabeth, Western Cape, 6045
Taiwan2 sites
Novartis Investigative Site
Taipei, 10002
Novartis Investigative Site
Taipei, 10449
Turkey (Türkiye)2 sites
Novartis Investigative Site
Istanbul, Fatih, 34098
Novartis Investigative Site
Istanbul, Kadikoy, 34722
United Kingdom2 sites
Novartis Investigative Site
Nottingham, NG5 1PB
Novartis Investigative Site
Oxford, OX3 7LE
About this study
Official title: 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)
Read the 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.
- Conditions
- Triple Negative Breast Neoplasms
- Being tested
- alpelisib, placebo, nab-paclitaxel
- Keywords
- Triple Negative Breast Cancer, alpelisib, BYL719, nab-paclitaxel, PIK3CA mutation, PTEN loss
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
alpelisibDrug
Also called BYL719
300 mg orally, once per day (QD), tablets
placeboDrug
Also called alpelisib-matching placebo
300 mg orally, once per day (QD), tablets
nab-paclitaxelDrug
Also called abraxane
100 mg/m^2 IV infusion, once per day (QD)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: 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. Receives: Drug: alpelisib; Drug: nab-paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 6 months
Secondary outcomes (12)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study start8 Jun 2020
- Primary completion31 May 2023
- Study completion5 Feb 2026
Why it stopped: The study was terminated following a strategic decision to halt recruitment due to persistently slow enrollment. This decision was not driven by any new or unexpected safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Triple Negative Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 137 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04251533
- Sponsor's protocol ID
- CBYL719H12301
- Other IDs
- 2024-511931-87-00, 2019-002637-11, 2019
- Acronym
- EPIK-B3
- Status last verified
- Aug 2026
- First submitted
- 30 Jan 2020
- Last updated
- 10 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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