Phase 1b/2 PIKTOR (serabelisib PI3Kα inhibitor + sapanisertib dual mTORC1/2 inhibitor)

This Phase 1b/2, multi-center, open-label umbrella study sponsored by Faeth Therapeutics tests “PIKTOR,” an all-oral combination of serabelisib (a PI3K-alpha inhibitor; also referenced as INK-1117 in some materials) plus sapanisertib (a dual mTORC1 and mTORC2 inhibitor), layered onto fulvestrant (an estrogen receptor degrader) in HR+/HER2- unresectable locally advanced or metastatic breast cancer. The trial uses dose escalation (e.g., Cohort A1 vs A2 higher dosing) to establish tolerability and a recommended regimen, while also looking for early signs of anti-tumor activity from deeper pathway “vertical” inhibition across PI3K→mTOR signaling. The key scientific/commercial angle is whether coordinated PI3K + mTOR blockade can overcome endocrine resistance beyond what single-node pathway targeting has achieved, potentially at doses that remain feasible for chronic administration. In current practice, most patients start with endocrine therapy plus a CDK4/6 inhibitor, then commonly move to endocrine therapy with targeted agents (often PI3K/AKT/mTOR-pathway agents in biomarker-selected subsets) and later to antibody-drug conjugates and/or chemotherapy as resistance accumulates.