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.

• Status: Not yet recruiting
• Trial end date: 2026-11-27
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: Fulvestrant

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 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).

• 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).

• Participant must show the presence of a PIK3CA mutation(s) determined by tissue either by a local laboratory using only CE-marked IVD assays such as QIAGEN Therascreen® PIK3CA RGQ PCR test or by a Novartis designated laboratory.

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 therapy with no treatment for metastatic disease

• Participant has received prior treatment with fulvestrant, any Phosphatidylinositol-3-Kinase (PI3K), mammalian Target of Rapamycin (mTOR) or Protein Kinase B (AKT) inhibitor

Other Inclusion and Exclusion Criteria do apply