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.

Conditions: Breast Cancer

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.

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.

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

Keywords: alpelisib fulvestrant advanced breast cancer phase iii hr-positive her-2 negative cdk4/6 inhibitor pik3ca mutation progression free survival aromatase inhibitor