ASCO 2026: VIKTORIA-1 Phase 3 — Gedatolisib Nearly Doubles PFS in PIK3CA-Mutant HR+ Breast Cancer with Better Toxicity Profile vs. Alpelisib

The Phase 3 VIKTORIA-1 trial (Abstract LBA1008), presented at ASCO 2026 by Dr. Sara Hurvitz, evaluated gedatolisib — a dual PI3K/mTOR inhibitor from Celcuity — in combination with fulvestrant or palbociclib in patients with HR-positive/HER2-negative PIK3CA-mutant advanced breast cancer who had progressed on a CDK4/6 inhibitor and aromatase inhibitor. Gedatolisib combinations nearly doubled progression-free survival versus the comparator arm (alpelisib + fulvestrant), with an objective response rate of 48.9% vs. 26.0%. A key differentiator was the toxicity profile: gedatolisib showed substantially lower rates of severe hyperglycemia and rash/diarrhea compared to alpelisib (Piqray) — adverse events that have significantly limited alpelisib adoption in clinical practice despite its FDA approval. PIK3CA mutations are present in approximately 40% of HR+ breast cancer patients, making this a large addressable population. Gedatolisib's simultaneous PI3K/mTOR dual inhibition offers mechanistic advantages over PI3Kα-selective inhibitors by blocking mTOR-mediated feedback reactivation of the PI3K pathway, a key mechanism of resistance. The trial results support gedatolisib as a potential best-in-class therapy for PIK3CA-mutant HR+ metastatic breast cancer post-CDK4/6 inhibitor, with regulatory submissions anticipated. The results were simultaneously published in the Journal of Clinical Oncology.