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

The FDA has formally accepted the new drug application (NDA) for gedatolisib (PF-05212384, PKI-587; Celcuity) in the treatment of hormone receptor–positive (HR+), HER2-negative (HER2–), PIK3CA wild-type advanced breast cancer and has granted it priority review. The Prescription Drug User Fee Act (PDUFA) goal date has been set for July 17, 2026.¹

The NDA submission by Celcuity is based on encouraging efficacy and safety data from the phase 3 VIKTORIA-1 (NCT05501886) trial that were showcased at the 2025 European Society for Medical Oncology (ESMO) Congress.^1,2

Phase 3 VIKTORIA-1 Trial: Design and Rationale

VIKTORIA-1 is a randomized, open-label clinical trial evaluating gedatolisib in combination with fulvestrant with or without palbociclib in adults with HR+/HER2– advanced breast cancer whose disease progressed on or after prior CDK4/6 inhibitor and aromatase inhibitor therapy.² Participants were randomly assigned 1:1:1 to receive gedatolisib, palbociclib, and fulvestrant (triplet); gedatolisib plus fulvestrant (doublet); or fulvestrant alone as the control arm.² The co–primary end point was progression-free survival (PFS) assessed by blinded independent central review, with secondary measures including overall survival and objective response rate (ORR).²

Gedatolisib is a multitarget inhibitor of all class I PI3K isoforms and both mTOR complexes (mTORC1 and mTORC2), designed to provide broader PAM pathway inhibition to counter adaptive mechanisms of resistance in advanced, endocrine-resistant tumor cells.¹

Efficacy Findings Presented at ESMO 2025

At the ESMO Congress, detailed efficacy outcomes from the VIKTORIA-1 PIK3CA wild-type cohort showed robust, clinically meaningful improvements in PFS with both gedatolisib regimens compared with fulvestrant alone.² The triplet regimen achieved a median PFS of 9.3 months vs 2 months for fulvestrant monotherapy, corresponding to a 76% reduction in the risk of disease progression or death (HR, 0.24; 95% CI, 0.17-0.35; P < .0001).² The doublet combination yielded a median PFS of 7.4 months with a 67% risk reduction relative to fulvestrant (HR, 0.33; 95% CI, 0.24-0.48; P < .0001).²

Across all combinations, ORRs were significantly higher than with the fulvestrant monotherapy, supporting the clinical activity of gedatolisib-based therapies.² This level of effect has been deemed unprecedented in this type of patient population and may establish a new benchmark in the second-line setting.²

Safety and Tolerability

Generally, the safety profile of gedatolisib combinations was manageable. Common adverse events included neutropenia and stomatitis, consistent with known effects of PAM pathway blockade and CDK4/6 inhibition.¹ Importantly, hyperglycemia, often a concern with PI3K inhibitors, was not observed at clinically significant rates in the VIKTORIA-1 cohort.¹ Low discontinuation rates due to treatment-related adverse events further support the tolerability of these regimens in a heavily pretreated population.¹

Regulatory Implications of Priority Review

This priority review designation shows that the FDA recognizes the potential therapeutic value of gedatolisib in the treatment of HR+/HER2– PIK3CA wild-type advanced breast cancer, a population with unmet medical needs.¹ The priority review designation indicates that the FDA would act on the new drug application (NDA) in an accelerated time frame. Another factor supporting Celcuity’s expeditious development pathway is that the NDA has been accepted into the Real-Time Oncology Review program.¹

Unmet Need in Advanced HR+/HER2– Breast Cancer

Breast cancer remains an established cause of morbidity and mortality due to malignancy, and the majority of these patients have been identified as having HR+ and HER2– disease. For patients whose disease becomes refractory to hormonal and CDK4/6 inhibition, a lack of effective therapies has been a concern, especially for patients whose tumors were PIK3CA wild type. Historically, targeting the PAM pathway has yielded benefits in select molecular subgroups, but until recently, there had been no practice-changing phase 3 evidence for patients with PIK3CA wild-type disease in the post-CDK4/6 inhibitor setting.¹

Conclusion

Gedatolisib, if approved by the PDUFA goal date, could provide an important treatment alternative for patients with HR+/HER2– breast cancer lacking PIK3CA mutation by offering a novel paradigm for overcoming endocrine and CDK4/6 inhibitor resistance. Continued follow-up to assess long-term outcomes, including overall survival and real-world effectiveness, will be essential to confirm the full clinical value of these findings.^1,2

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. LBA17 Gedatolisib (geda) + fulvestrant ± palbociclib (palbo) vs fulvestrant in patients (pts) with HR+/HER2–/PIK3CA wild-type (WT) advanced breast cancer (ABC): first results from VIKTORIA-1. Ann Oncol. 2025;36(suppl 2):S1562-S1563. doi:10.1016/j.annonc.2025.09.027