FDA Approves Gedatolisib for HR+/HER2- Advanced Breast Cancer

The FDA has approved gedatolisib (Revtorpyk; Celcuity), a pan-PI3K and mTORC1/2 inhibitor for patients with hormone receptor (HR)–positive, HER2–negative, locally advanced or metastatic breast cancer without a PIK3CA mutation whose disease progressed after at least one line of endocrine therapy.¹ The drug is approved for use in combination with fulvestrant, with or without palbociclib, and is the first agent in its class—targeting class I PI3K isoforms alongside both mTOR complexes—to reach the market.

A Long-Sought Target Finally Addressed

The PI3K/Akt/mTOR pathway has been a priority for oncology drug developers for roughly 2 decades, but achieving comprehensive pathway inhibition proved difficult until now, according to Celcuity CEO and cofounder Brian Sullivan. HR+/HER2– disease represents about 70% of all breast cancers, and roughly 60% of these tumors are PIK3CA wild-type, meaning a substantial share of patients could be candidates for the new therapy.

“For patients with HR+/HER2– locally advanced or metastatic breast cancer, there is an urgent need for new treatment options that can meaningfully increase the likelihood of survival without disease progression or death. With the approval of Revtorpyk, oncologists now have an effective new treatment option for these patients,” VIKTORIA-1 trial investigator Sara A. Hurvitz, MD, senior vice president and director, Clinical Research Division, and Smith Family Endowed Chair in Women’s Health, Fred Hutch Cancer Center, and professor and head, Division of Hematology and Oncology, University of Washington, School of Medicine, said in a statement.

Trial Data Show Meaningful PFS Gains

The approval rests on detailed results from the PIK3CA wild-type cohort of the phase 3 VIKTORIA-1 trial (NCT05501886), presented as a late-breaking oral presentation at the 2025 European Society for Medical Oncology Congress.² Findings showed that gedatolisib combined with fulvestrant plus palbociclib (the "triplet") achieved a median progression-free survival (PFS) of 9.3 months vs 2.0 months with fulvestrant alone—a 7.3-month improvement and a 76% reduction in the risk of progression or death (HR, 0.24; 95% CI, 0.17-0.35; P < .0001).

The objective response rate (ORR) was 31.5% for the triplet vs 1% for fulvestrant, with a median duration of response of 17.5 months. The gedatolisib doublet (gedatolisib plus fulvestrant, without palbociclib) showed a median PFS of 7.4 months vs 2.0 months with fulvestrant (a 5.4-month improvement, 67% risk reduction; HR, 0.33; 95% CI, 0.24-0.48; P < .0001), an ORR of 28.3%, and a median duration of response of 12.0 months.

Benefit was consistent across subgroups, with the triplet showing particularly strong results in pre/perimenopausal patients, those with endocrine therapy resistance, and those with visceral metastases. Among patients enrolled in the US and Canada specifically, median PFS reached 19.3 months with the triplet and 14.9 months with the doublet. Both regimens were generally well tolerated, with mostly low-grade treatment-related adverse events; the most notable grade 3 event was neutropenia (52.3% with the triplet, 0% with the doublet), whereas hyperglycemia occurred in just 9.2% (triplet) and 11.5% (doublet) of patients overall. Treatment discontinuation due to adverse events was low in both arms (2.3% and 3.1%, respectively).

Safety Profile Includes Stomatitis, Hyperglycemia Risks

The FDA label carries warnings for severe stomatitis, dermatologic reactions including rash, and hyperglycemia, which occurred in roughly half of patients across both combination arms.¹ Prescribers are advised to initiate prophylactic steroid-containing mouthwash before treatment starts and to monitor fasting glucose and hemoglobin A_1c levels throughout therapy. The drug also carries an embryo-fetal toxicity warning, with contraception recommended during treatment and for 2 weeks afterward.

Common adverse reactions across both regimens included cytopenias, nausea, fatigue, vomiting, elevated liver enzyme levels, and musculoskeletal pain.

What Comes Next for Gedatolisib?

Celcuity expects to launch gedatolisib commercially in the late third quarter of 2026 and plans an expanded access program to bridge patients to treatment before then. The company also intends to file a supplemental new drug application in the third quarter of 2026 seeking approval in the PIK3CA-mutated population, based on results from VIKTORIA-1's mutant cohort presented at the 2026 American Society of Clinical Oncology Annual Meeting. Gedatolisib is additionally being evaluated in the phase 3 VIKTORIA-2 trial (NCT06757634) among treatment-naive patients with advanced HR+/HER2– breast cancer and in a separate program for metastatic castration-resistant prostate cancer.

References

1. Celcuity announces FDA approval of Revtorpyk (gedatolisib) for the treatment of HR+/HER2-, PIK3CA wild-type locally advanced or metastatic breast cancer. News release. Celcuity Inc. July 14, 2026. Accessed July 15, 2026. https://ir.celcuity.com/news-releases/news-release-details/celcuity-announces-fda-approval-revtorpyktm-gedatolisib
2. Detailed results from PIK3CA wild-type cohort of phase 3 VIKTORIA-1 trial presented at 2025 ESMO Congress demonstrate potential for gedatolisib regimens to be practice changing for patients with HR+/HER2- advanced breast cancer. News release. Celcuity Inc. October 18, 2025. Accessed July 16, 2026. https://ir.celcuity.com/news-releases/news-release-details/detailed-results-pik3ca-wild-type-cohort-phase-3-viktoria-1