RLY-2608 + fulvestrant + ribociclib

This combination therapy comprises **RLY-2608**, a first-in-class, oral, allosteric, mutant- and isoform-selective PI3Kα inhibitor, administered with **fulvestrant** (an estrogen receptor antagonist) and **ribociclib** (a CDK4/6 inhibitor). It is under clinical investigation mainly for patients with **PIK3CA-mutant, HR-positive, HER2-negative advanced or metastatic breast cancer**. RLY-2608 is designed to selectively inhibit mutant PI3Kα (encoded by PIK3CA), avoiding the adverse effects typically associated with wild-type PI3Kα inhibition, such as hyperglycemia[3][4]. Fulvestrant blocks and degrades estrogen receptors, disrupting hormone-driven tumor growth. Ribociclib inhibits cyclin-dependent kinases 4 and 6, blocking cell cycle progression in tumor cells. This triple combination aims to maximize antitumor efficacy by targeting RTK/PI3K, hormone, and cell cycle pathways simultaneously. The combination is in clinical development with ongoing studies including dose escalation and expansion cohorts in breast and endometrial cancers with PIK3CA mutations[1][3][6].

Other names

KisqaliFaslodex