FDA Grants Priority Review to Gedatolisib for Advanced Breast Cancer

The FDA has accepted for filing a new drug application (NDA) for gedatolisib, an investigational PI3K and mTOR inhibitor, for the treatment of certain patients with advanced breast cancer.¹ The regulatory agency granted priority review for the application and assigned a Prescription Drug User Fee Act (PDUFA) target action date of July 17, 2026.

The NDA seeks approval for gedatolisib in combination with fulvestrant (Faslodex), with or without palbociclib (Ibrance), for the treatment of adult patients with hormone receptor-positive (HR+), HER2-negative (–), PIK3CA wild-type, locally advanced or metastatic breast cancer. This indication applies to patients whose disease has progressed on or after treatment with a CDK4/6 inhibitor and an aromatase inhibitor.

The submission was processed under the FDA’s Real-Time Oncology Review program, a pilot initiative designed to expedite the delivery of safe and effective cancer treatments to patients.² Gedatolisib previously received breakthrough therapy and fast track designations from the FDA.³

“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+/HER2– advanced breast cancer,” said Brian Sullivan, CEO and co-founder of Celcuity, in a news release.¹ “We believe the robust clinical dataset underlying this submission demonstrates the practice changing potential of gedatolisib. We are looking forward to collaborating with the FDA throughout the review process as we work towards a potential approval and commercial launch.”

Phase 3 VIKTORIA-1 Clinical Data

The regulatory filing is supported by results from the PIK3CA wild-type cohort of the phase 3 VIKTORIA-1 trial (NCT05501886).⁴ The randomized, open-label study evaluated the efficacy and safety of 2 gedatolisib-based regimens compared with fulvestrant monotherapy.

According to data presented at the 2025 European Society for Medical Oncology (ESMO) Congress, both gedatolisib combinations met their primary end points of significantly improving progression-free survival (PFS) as assessed by blinded independent central review. Patients receiving the triplet regimen of gedatolisib, fulvestrant, and palbociclib achieved a median PFS of 9.3 months (95% CI, 7.2–16.6), compared with 2.0 months (95% CI, 1.8–2.3) for those receiving fulvestrant alone. This represented a 76% reduction in the risk of disease progression or death (HR, 0.24; 95% CI, 0.17–0.35; P <.0001).⁵

The doublet regimen, consisting of gedatolisib and fulvestrant, also demonstrated superiority over the control arm, with a median PFS of 7.4 months (95% CI, 5.5–9.9). This conferred a 67% reduction in the risk of progression or death (HR, 0.33; 95% CI, 0.24–0.48; P <.0001). Objective response rates were notably higher in the investigational arms (32% for the triplet and 28.3% for the doublet) compared with 1% in the fulvestrant monotherapy group.

Safety and Tolerability

The safety profile of the gedatolisib regimens in VIKTORIA-1 was reported as manageable, with a low rate of treatment discontinuation due to treatment-related adverse events (2.3% for the triplet and 3.1% for the doublet). The most common adverse events included stomatitis and hyperglycemia. However, researchers noted that the incidence of grade 3/4 hyperglycemia was lower than that seen with isoform-specific PI3K inhibitors, and stomatitis was generally low-grade and resolvable within 2 weeks with prophylactic management.

Mechanism and Clinical Significance

Gedatolisib is a first-in-class multi-target inhibitor of the PI3K/AKT/mTOR (PAM) pathway. Unlike earlier-generation inhibitors that target specific PI3K isoforms or mTOR alone, gedatolisib provides comprehensive blockade of all 4 class I PI3K isoforms and mTORC1/2.¹ This pan-inhibition is intended to mitigate the adaptive cross-activation of the pathway that often occurs when only a single node is targeted, potentially overcoming endocrine resistance.

The focus on the PIK3CA wild-type population addresses a significant unmet need in the second-line setting. While PI3K inhibitors like alpelisib (Piqray) are currently approved for PIK3CA-mutated disease, therapeutic options for patients with wild-type status who progress on CDK4/6 inhibitors have historically been limited to fulvestrant monotherapy or chemotherapy, both of which offer modest PFS benefits.

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://tinyurl.com/mxzywcxd

2. Celcuity to initiate NDA Submission of gedatolisib in PIK3CA wild-type cohort in HR+/HER2- advanced breast cancer under FDA’s real-time oncology review program. News release. Celcuity Inc. August 27, 2025. Accessed January 20, 2026. https://tinyurl.com/bdes6m8k

3. Celcuity receives FDA fast track designation for gedatolisib in HR+/HER2- metastatic breast cancer and provides corporate update. News release. January 20, 2022. Accessed January 20, 2026. https://bit.ly/3nI7aui

4. Gedatolisib plus fulvestrant with or without palbociclib vs standard-of-care for the treatment of patients with advanced or metastatic HR+/​HER2- breast cancer (VIKTORIA-1) (VIKTORIA-1). ClinicalTrials.gov. Updated December 15, 2025. Accessed January 20, 2026. https://www.clinicaltrials.gov/study/NCT05501886

5. Hurvitz SA, Layman RM, Curigliano G, et al. Gedatolisib plus fulvestrant, with & without palbociclib, vs fulvestrant in patients with HR+/HER2-/PIK3CA wild-type advanced breast cancer: first results from VIKTORIA-1. Presented at: 2025 ESMO Annual Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA17.