Minneapolis-based Celcuity Inc. (Nasdaq: CELC) has received US FDA approval for Revtorpyk (gedatolisib), making it the first and only therapy to inhibit all class I PI3K isoforms and both mTOR complexes to reach regulatory approval. The indication covers adult patients with HR+/HER2− locally advanced or metastatic breast cancer without a detected PIK3CA mutation, following progression on at least one line of endocrine therapy in the metastatic setting — a biomarker-defined population that has lacked targeted options within the PI3K/AKT/mTOR pathway.
Revtorpyk is approved in combination with fulvestrant, with or without palbociclib, administered intravenously. The drug inhibits all four class I PI3K isoforms (α, β, δ, γ) alongside mTORC1 and mTORC2, suppressing downstream AKT signaling while blocking the compensatory feedback reactivation that limits the efficacy of single-node inhibitors. This broad coverage of the PI3K/AKT/mTOR axis is the mechanistic rationale for its activity in PIK3CA wild-type tumors, where pathway activation occurs through mechanisms other than PIK3CA mutation.
The approval is supported by data from the Phase III VIKTORIA-1 trial, an open-label, global, randomized study in patients with locally advanced or metastatic HR+/HER2− breast cancer who had progressed on CDK4/6 therapy and an aromatase inhibitor. In the PIK3CA wild-type cohort, the Revtorpyk triplet (gedatolisib plus palbociclib and fulvestrant) demonstrated a median progression-free survival of 9.3 months versus 2.0 months with fulvestrant alone (HR=0.24; 95% CI: 0.17–0.35; p<0.0001), with an objective response rate of 32% compared to 1%. The doublet (gedatolisib plus fulvestrant) also showed statistically significant improvement, with a median PFS of 7.4 months versus 2.0 months (HR=0.33; p<0.0001).