Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant in Participants With HR-postitive (HR+), HER2-negative, Advanced Breast Cancer After Treatment With a CDK4/6 Inhibitor and an Aromatase Inhibitor.

Last Update: Nov 14, 2024

EPIK-B5: A Phase III, Randomized, Double-blind, Placebo-controlled Study of Alpelisib in Combination With Fulvestrant for Men and Postmenopausal Women With HR-positive, HER2-negative Advanced Breast Cancer With a PIK3CA Mutation, Who Progressed on or After Aromatase Inhibitor and a CDK4/6 Inhibitor

ClinicalTrials.gov Identifier:

NCT05038735

Novartis Reference Number:CBYL719C2303

See if you Pre-qualify

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 study is to complement Study CBYL719C2301 (SOLAR-1) and obtain more comprehensive data on the efficacy and safety of alpelisib (BYL719) in combination with fulvestrant compared with placebo plus fulvestrant in men or postmenopausal women with HR-positive, HER2-negative advanced breast cancer with a PIK3CA mutation who progressed or relapsed on or after treatment with an AI plus a CDK4/6 inhibitor. This is a Phase III, randomized, double-blind, placebo-controlled, international, multi-center trial. Approximately 234 men and postmenopausal women will be randomized to either alpelisib plus fulvestrant or alpelisib-matching placebo plus fulvestrant. Randomization will follow a 1:1 randomization ratio and be stratified by presence of lung and/or liver metastases (yes vs. no) and setting at last prior CDK4/6 inhibitor therapy (adjuvant vs metastatic).

Study treatment with alpelisib plus fulvestrant or alpelisib-matching placebo plus fulvestrant will be initiated on Cycle 1 Day 1, and will continue until disease progression per RECIST v1.1 as per BIRC assessment, start of new antineoplastic therapy, death, lost to follow-up, or withdrawal of consent. A cycle is defined as 28 days.

Participants randomized to the alpelisib-matching placebo plus fulvestrant arm who have disease progression per RECIST v1.1 as assessed by BIRC will have the option to crossover to be treated with alpelisib plus fulvestrant.

Unblinding a single participant at a site will be permitted after disease progression confirmed by BIRC after discussion with the Novartis team to determine eligibility for cross-over to treatment with alpelisib plus fulvestrant.

Condition

Breast Cancer

Phase

Phase3

Overall Status

Recruiting

Number of Participants

234

Start Date

Nov 29, 2021

Completion Date

Dec 29, 2027

Gender

All

Age(s)

18 Years - (Adult, Older Adult)

Interventions

Drug

Alpelisib

Alpelisib (tablets) administered at 300mg orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle.

Drug

Alpelisib-matching placebo

Alpelisib-matching placebo (tablets) administered orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle.

Drug

Fulvestrant

Fulvestrant (prefilled syringe) 500mg administered intramuscularly at Cycle 1 Day 1 and 15 and then at Day 1 of each subsequent cycle (each cycle is 28 days).

Eligibility Criteria

Inclusion Criteria:

* Participant is an adult ≥ 18 years old at the time of informed consent and has signed informed consent before any trial related activities and according to local guidelines.
* If female, then the participant must be in postmenopausal status. Postmenopausal status is defined either by: prior bilateral oophorectomy, age ≥60 or age \<60 and amenorrheic for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range per local normal range.
* Participant has a histologically and/or cytologically confirmed diagnosis of ER+ and/or PgR+ breast cancer by local laboratory.
* Participant has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (Fluorescent in situ hybridization (FISH), Chromogenic in situ hybridization (CISH), or Silver-enhanced in situ hybridization (SISH)) test is required by local laboratory testing.
* Participant has at least one measurable lesion as per RECIST v1.1 criteria as assessed by Investigator (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation).
* Participant has recurrence or progression of disease during or after combined AI (i.e. letrozole, anastrozole, exemestane) and CDK4/6 inhibitor therapy. The combined AI and CDK4/6 inhibitor therapy does not need to be the latest treatment regimen (including adjuvant setting).
* Participant has received ≤2 prior lines of systemic therapies overall in the metastatic setting, of which a maximum of 1 line of prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy).
* Participant must show the presence of a PIK3CA mutation(s) determined in tumor tissue prior ro enrollment either by a Novartis designated laboratory or in tumor tissue or plasma ctDNA by a local laboratory using a Food and Drug Administration (FDA)-approved PIK3CA Companion Diagnostics (CDx) test for alpelisib or the CE-IVD QIAGEN Therascreen® PIK3CA RGQ PCR test.

Exclusion Criteria:

* Participant with symptomatic visceral disease that makes the participant ineligible for endocrine therapy (ET) per the investigator's best judgment.
* Participant who relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine/endocrine-based therapy with no treatment for metastatic disease
* Participant has received prior treatment with fulvestrant, any oral selective estrogen receptor degrader (SERDs), any Phosphatidylinositol-3-Kinase (PI3K), mammalian Target of Rapamycin (mTOR) or Protein Kinase B (AKT) inhibitor

Other Inclusion and Exclusion Criteria do apply

Novartis Investigative Site

Recruiting

Sint Niklaas,Oost Vlaanderen,9100,Belgium

Novartis Investigative Site

Recruiting

Bruxelles,1000,Belgium

Novartis Investigative Site

Recruiting

Bruxelles,1200,Belgium

Novartis Investigative Site

Recruiting

Gent,9000,Belgium

Novartis Investigative Site

Recruiting

Leuven,3000,Belgium

Novartis Investigative Site

Recruiting

Liege,4000,Belgium

Novartis Investigative Site

Recruiting

Plovdiv,4004,Bulgaria

Novartis Investigative Site

Recruiting

Sofia,1303,Bulgaria

Novartis Investigative Site

Recruiting

Sofia,1750,Bulgaria

Novartis Investigative Site

Recruiting

Sofia,1756,Bulgaria

Novartis Investigative Site

Recruiting

Oshawa,Ontario,L1g 2b9,Canada

Novartis Investigative Site

Recruiting

Ottawa,Ontario,K1h 8l6,Canada

Novartis Investigative Site

Recruiting

Brno,Czech Republic,656 53,Czechia

Novartis Investigative Site

Recruiting

Novy Jicin,Czech Republic,74101,Czechia

Novartis Investigative Site

Recruiting

Praha 10,100 34,Czechia

Novartis Investigative Site

Recruiting

Praha 4,140 59,Czechia

Novartis Investigative Site

Recruiting

Praha,12808,Czechia

Novartis Investigative Site

Recruiting

Odense C,Dk 5000,Denmark

Novartis Investigative Site

Recruiting

Aalborg,Dk 9000,Denmark

Novartis Investigative Site

Recruiting

Copenhagen,Dk-2100,Denmark

Novartis Investigative Site

Recruiting

Helsinki,00029,Finland

Novartis Investigative Site

Recruiting

Tampere,Fin-33521,Finland

Novartis Investigative Site

Recruiting

Lyon,69373,France

Novartis Investigative Site

Recruiting

Marseille,13273,France

Novartis Investigative Site

Recruiting

Montpellier,34298,France

Novartis Investigative Site

Recruiting

Paris 10,75475,France

Novartis Investigative Site

Recruiting

Besancon Cedex,25030,France

Novartis Investigative Site

Recruiting

Paris,75970,France

Novartis Investigative Site

Recruiting

Clermont-Ferrand,63011,France

Novartis Investigative Site

Recruiting

Valenciennes,59300,France

Novartis Investigative Site

Recruiting

La Roche sur Yon Cedex,85925,France

Novartis Investigative Site

Recruiting

Villejuif,94800,France

Novartis Investigative Site

Recruiting

Ravensburg,88214,Germany

Novartis Investigative Site

Recruiting

Augsburg,86150,Germany

Novartis Investigative Site

Recruiting

Berlin,13353,Germany

Novartis Investigative Site

Recruiting

Essen,45136,Germany

Novartis Investigative Site

Recruiting

Koeln,50937,Germany

Novartis Investigative Site

Recruiting

Luebeck,23538,Germany

Novartis Investigative Site

Recruiting

Muenchen,81377,Germany

Novartis Investigative Site

Recruiting

Athens,Gr 115 22,Greece

Novartis Investigative Site

Recruiting

Patras,265 00,Greece

Novartis Investigative Site

Recruiting

Budapest,H 1122,Hungary

Novartis Investigative Site

Recruiting

Gyor,H-9024,Hungary

Novartis Investigative Site

Recruiting

Dublin,D03 vx82,Ireland

Novartis Investigative Site

Recruiting

Dublin,Dublin 9,Ireland

Novartis Investigative Site

Recruiting

Dublin 4,Do4,Ireland

Novartis Investigative Site

Recruiting

Roma,RM,00168,Italy

Novartis Investigative Site

Recruiting

Genova,GE,16132,Italy

Novartis Investigative Site

Recruiting

Terni,TR,05100,Italy

Novartis Investigative Site

Recruiting

Milano,MI,20132,Italy

Novartis Investigative Site

Recruiting

Bari,BA,70124,Italy

Novartis Investigative Site

Recruiting

Napoli,80131,Italy

Novartis Investigative Site

Recruiting

Milano,MI,20133,Italy

Novartis Investigative Site

Recruiting

Bergamo,BG,24127,Italy

Novartis Investigative Site

Recruiting

Novara,28100,Italy

Novartis Investigative Site

Recruiting

Milano,MI,20141,Italy

Novartis Investigative Site

Recruiting

Bologna,BO,40138,Italy

Novartis Investigative Site

Recruiting

Rozzano,MI,20089,Italy

Novartis Investigative Site

Recruiting

Padova,PD,35100,Italy

Novartis Investigative Site

Recruiting

Brindisi,BR,72100,Italy

Novartis Investigative Site

Recruiting

Palermo,PA,90127,Italy

Novartis Investigative Site

Recruiting

Aviano,PN,33081,Italy

Novartis Investigative Site

Recruiting

Firenze,FI,50134,Italy

Novartis Investigative Site

Recruiting

Opole,45 054,Poland

Novartis Investigative Site

Recruiting

Bydgoszcz,85 796,Poland

Novartis Investigative Site

Recruiting

Gdansk,80 952,Poland

Novartis Investigative Site

Recruiting

Coimbra,3000-075,Portugal

Novartis Investigative Site

Recruiting

Lisboa,1099 023,Portugal

Novartis Investigative Site

Recruiting

Lisboa,1400-038,Portugal

Novartis Investigative Site

Recruiting

Lisboa,1500 650,Portugal

Novartis Investigative Site

Recruiting

Lisboa,1649 035,Portugal

Novartis Investigative Site

Recruiting

Porto,4200-072,Portugal

Novartis Investigative Site

Recruiting

Floresti,Cluj,407280,Romania

Novartis Investigative Site

Recruiting

Craiova,Dolj,200347,Romania

Novartis Investigative Site

Recruiting

Constanta,905900,Romania

Novartis Investigative Site

Recruiting

Timisoara,300425,Romania

Novartis Investigative Site

Recruiting

Kosice,041 91,Slovakia

Novartis Investigative Site

Recruiting

Bratislava,Slovak Republic,83310,Slovakia

Novartis Investigative Site

Recruiting

Bratislava,812 50,Slovakia

Novartis Investigative Site

Recruiting

Badajoz,Extremadura,06080,Spain

Novartis Investigative Site

Recruiting

Malaga,Andalucia,29011,Spain

Novartis Investigative Site

Recruiting

A Coruna,Galicia,15009,Spain

Novartis Investigative Site

Recruiting

Sevilla,Andalucia,41013,Spain

Novartis Investigative Site

Recruiting

Pozuelo de Alarcon,Madrid,28223,Spain

Novartis Investigative Site

Recruiting

Oviedo,Asturias,33011,Spain

Novartis Investigative Site

Recruiting

Madrid,28040,Spain

Novartis Investigative Site

Recruiting

Jerez,Cadiz,11407,Spain

Novartis Investigative Site

Recruiting

Zaragoza,50009,Spain

Novartis Investigative Site

Recruiting

Lerida,Cataluna,25198,Spain

Novartis Investigative Site

Recruiting

Barcelona,Catalunya,08036,Spain

Worldwide Contacts

If the location of your choosing does not feature any contact detail, please reach out using the information below.

Novartis Pharmaceuticals

Phone: +41613241111

Email: [email protected]