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.

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

Last Update: Feb 28, 2023

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.

Condition

Breast Cancer

Phase

Phase 3

Overall status

Recruiting

Start date

Nov 29, 2021

Completion date

Sep 23, 2026

Gender

All

Age(s)

18 Years and older (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

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).

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.

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 locally and confirmed centrally by BIRC (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). The central confirmation by BIRC must be received prior to randomization
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 ≤1 line of prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy) and participant has received ≤2 prior lines of systemic therapies overall in the metastatic setting.
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