FDA to Review Gedatolisib NDA in HR+/HER2–, PIK3CA Wild-Type Advanced Breast Cancer

The FDA has agreed to review a new drug application (NDA) for gedatolisib for the treatment of patients with hormone receptor–positive, HER2-negative advanced breast cancer under its Real-Time Oncology Review program (RTOR).1

The application is supported by topline data from the PIK3CA wild-type cohort in the phase 3 VIKTORIA-1 trial (NCT05501886).

In VIKTORIA-1, patients in the PIK3CA wild-type cohort who were treated with gedatolisib, fulvestrant (Faslodex), and palbociclib (Ibrance) achieved a statistically significant and clinically meaningful progression-free survival (PFS) benefit, reducing the risk of disease progression or death by 76% vs fulvestrant alone (HR, 0.24; 95% CI, 0.17-0.35; P < .0001). 2 The median PFS was 9.3 months vs 2.0 months with the triplet vs fulvestrant monotherapy.

Additionally, treatment with gedatolisib and fulvestrant reduced the risk of disease progression or death by 67% compared with fulvestrant monotherapy (HR, 0.33; 95% CI, 0.24-0.48; P < .0001). The median PFS was 7.4 months vs 2.0 months with the doublet vs fulvestrant monotherapy.

Celcuity, the developer of gedatolisib, is expected to initiate rolling submission of its NDA for the novel agent in September 2025.1 Completion of the NDA submission is anticipated for the fourth quarter of 2025.

“On the heels of announcing positive pivotal data last month, we are pleased that the FDA agreed to review our NDA application for gedatolisib under the RTOR program,” Brian Sullivan, CEO and cofounder of Celcuity, stated in a news release. “Gedatolisib previously received both breakthrough therapy and fast track designations based on our promising preliminary clinical data.”

VIKTORIA-1 Trial Design

The open-label VIKTORIA-1 study is evaluating gedatolisib plus fulvestrant with or without palbociclib compared with fulvestrant alone in adults with locally advanced or metastatic hormone receptor–positive, HER2-negative breast cancer after disease progression on or after CDK4/6 and aromatase inhibitors (AIs).3

Eligible patients are at least 18 years of age with a histologically or cytologically confirmed diagnosis of locally advanced or metastatic breast cancer.2 Of note, premenopausal and perimenopausal women are allowed to enroll if amenable to receiving an LHRH agonist and have received concomitant treatment with an LHRH agonist before or on cycle 1 of study treatment. Patients are also required to have a confirmed diagnosis of estrogen receptor–positive and/or progesterone receptor–positive disease, based on the most recent tumor biopsy that uses an assay consistent with local standards; documented HER2 negativity per immunohistochemistry; adequate archival or fresh tumor tissue for the analysis of PIK3CA mutational status; experienced disease progression on or after a CDK4/6 inhibitor plus an AI; and documented radiological disease progression on or after the last prior treatment with radiologically evaluable disease per RECIST 1.1 criteria.

Common eligibility criteria were also required, including an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and adequate bone marrow, hepatic, renal, and coagulation function.

The primary end point of the study is PFS; secondary end points include overall survival, overall response rate, duration of response, time to response, clinical benefit rate, quality of life, and safety.

“The FDA’s decision further highlights the urgent need for more efficacious therapies than those currently available for patients with hormone receptor–positive, HER2-negative advanced breast cancer who have received prior treatment with a CDK4/6 inhibitor. We look forward to working with the FDA to complete the review of our NDA for gedatolisib,” Sullivan added in the news release.1

References

1. 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. August 27, 2025. Accessed August 28, 2025. https://ir.celcuity.com/press-releases
2. Celcuity announces clinically meaningful improvement in both progression-free survival (“PFS”) primary endpoints from PIK3CA wild-type cohort of phase 3 VIKTORIA-1 trial. News release. Celcuity. July 28, 2025. Accessed August 28, 2025. https://ir.celcuity.com/press-releases/
3. Gedaolisib plus fulvestrant with or without palbociclib vs standard-of-care for the treatment of patients with advanced or metastatic HR+/HER- breast cancer (VIKTORIA-1) (VIKTORIA-1). ClincialTrials.gov. Updated June 24, 2025. Accessed August 28, 2025. https://www.clinicaltrials.gov/study/NCT05501886