FULL APPROVAL

FDA approves Celcuity's REVTORPYK, first pan-PI3K/mTOR drug, in HR+/HER2- breast cancer

The approval rests on VIKTORIA-1 data showing gedatolisib cut progression risk 76% with palbociclib and 67% without it, versus fulvestrant alone.

The FDA approved REVTORPYK (gedatolisib) for HR+/HER2-, PIK3CA wild-type, locally advanced or metastatic breast cancer after progression on endocrine therapy.

By AppliedXLJuly 14, 2026Trial NCT05501886

Executive Summary

The FDA approved gedatolisib for a defined slice of HR+/HER2- advanced breast cancer, giving Celcuity its first commercial drug and the first approved therapy that blocks the PI3K/AKT/mTOR pathway across all its major nodes rather than a single target.
The clearance rests on a randomized Phase 3 comparison against fulvestrant alone, where both gedatolisib combinations reduced the risk of progression or death by wide margins with high statistical confidence.
The approval lands in a field where several other PI3K, mTOR, and PAM-pathway programs in breast cancer have failed or been discontinued, positioning gedatolisib as the pathway's first approved success rather than another entrant testing an unproven mechanism.
Celcuity's second Phase 3 trial testing gedatolisib as a first-line combination is still enrolling, and its label's practical reach will depend on how oncologists sequence it against other post-CDK4/6 options.

The approval

Celcuity Inc. said the FDA approved REVTORPYK (gedatolisib) on July 14, 2026, for adult patients with HR+/HER2- locally advanced or metastatic breast cancer without a detectable PIK3CA mutation who progressed on at least one prior line of endocrine therapy. The decision came three days ahead of the drug's July 17, 2026 PDUFA goal date, under a priority review the FDA granted when it accepted the New Drug Application in January 2026. The company said REVTORPYK is the first and only FDA-approved therapy that inhibits all four class I PI3K isoforms along with both mTOR complexes, mTORC1 and mTORC2, rather than a single node of the pathway. Celcuity+1

Probability of Success

Endpoint Met97%

Completes48%

Clinical Significance87%

Regulatory89%

The trial and the result

The approval is based on the PIK3CA wild-type cohort of VIKTORIA-1 (NCT05501886), an open-label, randomized Phase 3 trial that enrolled 701 patients across the United States, Argentina, Greece, Poland, Belgium and Brazil, comparing gedatolisib plus fulvestrant, with or without palbociclib, against fulvestrant alone. The trial's registered primary endpoint is progression-free survival in the PIK3CA wild-type and mutant cohorts. In the wild-type cohort, median PFS with the triplet was 9.3 months versus 2.0 months with fulvestrant, a hazard ratio of 0.24 (95% CI: 0.17-0.35, p<0.0001), while the doublet reached 7.4 months versus 2.0 months, a hazard ratio of 0.33 (95% CI: 0.24-0.48, p<0.0001). The company frames those hazard ratios as a 76% and 67% reduction in the risk of progression or death for the triplet and doublet, respectively. Objective response rate was 32% for the triplet and 28% for the doublet against 1% for fulvestrant, with median duration of response of 17.5 and 12.0 months. NCT05501886+1

Why this pathway mattered

Celcuity CEO Brian Sullivan said the PI3K/AKT/mTOR pathway is one of the most important targets in cancer, but comprehensively inhibiting it has stymied researchers and drug developers for nearly two decades, and that REVTORPYK is the first pan-PI3K, mTORC1/2 inhibitor to reach approval. That framing tracks the landscape: PI3K-targeted programs in breast cancer have shown a 67% Phase 3 termination or failure pattern among the small set of comparable trials tracked for this target-indication pair, and 11 distinct sponsors have recorded failures pursuing PI3K in breast cancer. Six active industry trials are still testing PI3K-directed drugs in breast cancer, including Hoffmann-La Roche's inavolisib and Faeth Therapeutics' sapanisertib, both single-target PAM inhibitors rather than the pan-pathway approach gedatolisib takes. That distinction, comprehensive blockade of all four Class I PI3K isoforms plus both mTOR complexes versus inhibition of one node, is the mechanistic rationale Celcuity has cited for why single-target PAM inhibitors allow cross-activation of the uninhibited components, limiting durable pathway suppression, while gedatolisib's broader blockade is intended to close that escape route. Celcuity+1

Development history

Gedatolisib carried both Breakthrough Therapy and Fast Track designations heading into the submission, and the NDA was reviewed under the FDA's Real-Time Oncology Review program intended to shorten review timelines. VIKTORIA-1's primary completion date moved three times over the trial's life, from September 2024 to March 2025, then June 2025, then June 2026, before the trial moved to Active, not recruiting status in December 2025. Enrollment held flat at its 701-patient target through that period, consistent with a trial that finished recruiting on schedule rather than one that expanded or contracted its target. A second Phase 3 trial, VIKTORIA-2, is testing gedatolisib with a CDK4/6 inhibitor and fulvestrant as first-line treatment and is still enrolling patients. Celcuity+1

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