FDA Grants Priority Review to Gedatolisib for HR+, HER2-Negative Advanced Breast Cancer

The FDA has accepted and granted priority review to a new drug application (NDA) seeking the approval of gedatolisib (PF-05212384) for the treatment of patients with hormone receptor–positive, HER2-negative, PIK3CA wild-type advanced breast cancer.¹

The submission was supported by clinical data from the PIK3CA wild-type cohort of the phase 3 VIKTORIA-1 trial (NCT05501886). Findings from the trial presented at the 2025 ESMO Congress showed that patients in this population who received gedatolisib plus fulvestrant (Faslodex) and palbociclib (Ibrance; n = 131) achieved a median progression-free survival (PFS) of 9.3 months (95% CI, 7.2-16.6) vs 2.0 months (95% CI, 1.8-2.3) with fulvestrant alone (n = 131; adjusted HR, 0.24; 95% CI, 0.17-0.35; P < .0001).² Furthermore, patients who received gedatolisib plus fulvestrant alone (n = 130) achieved a median PFS of 7.4 months (95% CI, 5.5-9.9), conferring a benefit compared with fulvestrant monotherapy (HR, 0.33; 95% CI, 0.24-0.48; P < .0001).

The FDA has set a Prescription Drug User Fee Act (PDUFA) goal date of July 17, 2026, for this decision.¹ The NDA was submitted under the FDA’s Real-Time Oncology Review program, which is designed to facilitate shorter regulatory review periods.

“The FDA’s acceptance of our NDA for gedatolisib and the assignment of a PDUFA goal date is a pivotal milestone in our efforts to bring a much-needed new treatment option to patients with HR-positive/HER2-negative advanced breast cancer,” Brian Sullivan, chief executive officer and cofounder of Celcuity Inc, the developer of gedatolisib, stated in a news release. “We believe the robust clinical dataset underlying this submission demonstrates the practice changing potential of gedatolisib.”

What is the mechanism of action of gedatolisib, and how does it differ from other PAM pathway inhibitors?

Gedatolisib is an investigational, multi-target PI3K/AKT/mTOR (PAM) inhibitor. It is designed to potently target all 4 class I PI3K isoforms, as well as mTORC1 and mTORC2, to induce a comprehensive blockade of the PAM pathway. The mechanism of action of gedatolisib is highly differentiated from currently approved single-target inhibitors of the PAM pathway. In many cases, the inhibition of only a single PAM component results in cross-activation of uninhibited components, which can limit the suppression of the pathway’s activity.

Gedatolisib’s comprehensive inhibition enables full suppression of the PAM pathway by minimizing this adaptive cross-activation. Furthermore, unlike single-target inhibitors, gedatolisib has demonstrated comparable potency and cytotoxicity in both PIK3CA-mutant and –wild-type breast tumor cells during nonclinical studies and early clinical trials.

What was the design of the VIKTORIA-1 trial?

VIKTORIA-1 enrolled pre- and post-menopausal women, as well as men, with hormone receptor–positive, HER2-negative advanced breast cancer who had progressed on or after treatment with a CDK4/6 inhibitor plus a nonsteroidal aromatase inhibitor.² Patients could have received no more than 2 prior lines of endocrine therapy for advanced breast cancer. A total of 392 patients with PIK3CA wild-type disease were randomly assigned 1:1:1 to receive fulvestrant at 500 mg on days 1 and 15 of cycle 1, then every 4 weeks thereafter (arm C); fulvestrant plus gedatolisib at 180 mg once weekly for 3 weeks on and 1 week off (arm B); or fulvestrant plus gedatolisib and palbociclib at 125 mg daily for 21 days on and 7 days off (arm A).

PFS between arms A and C and between arms B and C served as the coprimary end points. Secondary end points included OS, overall response rate (ORR), safety, and quality of life.

What additional efficacy findings were seen in VIKTORIA-1?

At the May 30, 2025, data cutoff, the median OS in arm A was 23.7 months (95% CI, 21.4-not evaluable [NE]) vs 18.5 months (95% CI, 15.8-NE) in arm C (adjusted HR, 0.69; 95% CI, 0.43-1.12; P = .1328). In arm B, the median OS was not reached ([NR]; 95% CI, NE-NE), conferring a benefit compared with arm C (adjusted HR, 0.74; 95% CI, 0.46-1.19; P = .2122).

The ORRs were 31.5% in arm A, 28.3% in arm B, and 1.0% in arm C. Most responses were partial. Notably, 1 complete response was reported in arm A.

What is the safety profile of gedatolisib?

The most common any-grade adverse effects observed across arms A, B, and C, respectively, were stomatitis (69.2%; 56.9%; 0%), neutropenia (65.4%; 1.5%; 0.8%), nausea (43.8%; 43.1%; 3.3%), rash (27.7%; 32.3%; 0%), vomiting (27.7%; 23.1%; 0.8%), fatigue (22.3%; 20.8%; 4.1%), diarrhea (16.9%; 12.3%; 0%), and hyperglycemia (9.2%; 11.5%; 0%).

References

1. Celcuity announces FDA acceptance of new drug application for gedatolisib in HR+/HER2-/PIK3CA wild-type advanced breast cancer. News release. Celcuity Inc. January 20, 2026. Accessed January 20, 2026. https://ir.celcuity.com/news-releases/news-release-details/celcuity-announces-fda-acceptance-new-drug-application
2. Hurvitz SA, Layman RM, Curigliano G, et al. Gedatolisib plus fulvestrant, with and without palbociclib, vs fulvestrant in patients with HR+/HER2-/PIK3CA wild-type advanced breast cancer: first results from VIKTORIA-1. Ann Oncol. 2025;36(suppl 2):S1562-S1563. doi:10.1016/j.annonc.2025.09.027