Celcuity gedatolisib gains NCCN Category 1 status in breast cancer
Celcuity has announced that REVTORPYK (gedatolisib), its newly approved pan-PI3K and mTOR inhibitor, has been included in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines as a preferred Category 1 second-line and subsequent-line therapy for adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer without a detected PIK3CA mutation. The listing, which covers gedatolisib used in combination with fulvestrant with or without palbociclib, arrived just over a fortnight after the US Food and Drug Administration granted approval on 14 July 2026.
Category 1 designation in the NCCN framework reflects uniform consensus among panel members based on high-level evidence, making it one of the most commercially significant endorsements an oncology drug can receive in the US market. Oncologists, payers, and hospital formulary committees routinely use the guidelines to inform prescribing and reimbursement decisions, and a preferred Category 1 label at launch removes a meaningful barrier to uptake.
The clinical case
The FDA approval and NCCN listing both rest on data from the PIK3CA wild-type cohort of VIKTORIA-1, a global, open-label Phase 3 randomised trial. In that cohort, patients treated with the gedatolisib triplet (gedatolisib plus palbociclib plus fulvestrant) achieved a median progression-free survival of 9.3 months against 2.0 months for fulvestrant alone, a difference of 7.3 months with a hazard ratio of 0.24 (95% CI: 0.17–0.35; p less than 0.0001). The objective response rate was 32% versus 1%, with a median duration of response of 17.5 months. The doublet (gedatolisib plus fulvestrant) also showed meaningful benefit, with a 5.4-month PFS improvement over fulvestrant and an ORR of 28%.
The safety profile carries notable tolerability considerations. Stomatitis was the most prominent adverse event, occurring in 72% of patients on the triplet (Grade 3 in 22%) and 58% on the doublet (Grade 3 in 12%). Hyperglycaemia and rash were also common, consistent with the mechanism of broad PI3K and mTOR pathway suppression. Prophylactic steroid-containing mouthwash is required under the prescribing information.
Igor Gorbachevsky, Chief Medical Officer of Celcuity, said the NCCN inclusion "highlights the clinical relevance of this treatment option" and should support "informed treatment decision-making" for patients in this setting.
Market context and competitive landscape
Gedatolisib is positioned as the only approved inhibitor to block all four class I PI3K isoforms as well as both mTOR complexes, distinguishing it mechanistically from alpelisib, which targets PI3K-alpha selectively and is indicated in the PIK3CA-mutant population. The two agents therefore address complementary patient segments: alpelisib for PIK3CA-mutant tumours, gedatolisib for the wild-type cohort that until now lacked a targeted PI3K-pathway option beyond CDK4/6 combinations.
The broader HR+/HER2- metastatic breast cancer landscape is intensely competitive, with approved agents spanning CDK4/6 inhibitors, AKT inhibitors, antibody-drug conjugates, and endocrine backbones. The VIKTORIA-1 PFS data and the speed of NCCN adoption will be important commercial signals, but longer-term overall survival data remain awaited.
Celcuity expects REVTORPYK to be commercially available in the US in the late third quarter of 2026. An expanded access programme is in place for eligible patients ahead of launch. The company is also running VIKTORIA-2, a Phase 3 programme evaluating gedatolisib as a first-line treatment in two HR+/HER2- breast cancer cohorts, as well as a Phase 1/2 study in metastatic castration-resistant prostate cancer.