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 Hurvitz, MD, senior vice president, Clinical Research Division, Fred Hutchinson Cancer Center, Smith Family Endowed Chair in Women’s Health, 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 the PIK3CA-mutant cohort of the phase 3 VIKTORIA-1 trial (NCT05501886), a global, open-label study that compared gedatolisib-based regimens with fulvestrant alone in patients who had progressed on prior CDK4/6 inhibitor therapy and an aromatase inhibitor.

Findings demonstrated that gedatolisib-based regimens reduced the risk of disease progression or death by roughly 50% compared with alpelisib plus fulvestrant.² Among 362 patients randomly assigned 3:3:1 to a gedatolisib triplet (gedatolisib, palbociclib, and fulvestrant), alpelisib plus fulvestrant, or a gedatolisib doublet (gedatolisib plus fulvestrant), the triplet achieved a median progression-free survival (PFS) of 11.1 months vs 5.6 months for alpelisib/fulvestrant (HR, 0.50; 95% CI, 0.37-0.68; P < .0001), while the doublet achieved a median PFS of 11.3 months vs the same 5.6-month comparator (HR, 0.51; 95% CI, 0.33-0.79; P < .0013).

The triplet also produced a higher objective response rate (48.9% vs 26.0%) and a longer median duration of response (15.7 vs 7.5 months) than alpelisib/fulvestrant, while the doublet showed an objective response rate of 35.7% and a median duration of response of 24.2 months; investigators noted that the triplet's median PFS and objective response rate were the highest yet reported in a phase 3 trial for this second-line HR+/HER2- setting.

Discontinuation due to treatment-related adverse events was lower with the gedatolisib triplet (2.6%) and doublet (3.8%) than with alpelisib/fulvestrant (7.1%), and hyperglycemia occurred far less frequently with gedatolisib regimens (all-grade rates of 15.0% and 11.5% for the triplet and doublet, respectively, vs 57.9% for alpelisib/fulvestrant), though stomatitis was more common with gedatolisib (all-grade rates of 61.4% and 61.5% vs 34.2%).

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 enzymes, 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. Celcuity. News release. July 14, 2026. Accessed July 15, 2026. https://ir.celcuity.com/news-releases/news-release-details/celcuity-announces-fda-approval-revtorpyktm-gedatolisib
2. Caffrey M. In VIKTORIA-1, gedatolisib combos cut risk of progression by half vs alpelisib in PIK3CA-mutant advanced breast cancer. AJMC^®. June 19, 2026. Accessed July 15, 2026. https://www.ajmc.com/view/in-viktoria-1-gedatolisib-combos-cut-risk-of-progression-by-half-vs-alpelisib-in-pik3ca-mutant-advanced-breast-cancer