FDA Accepts New Drug Application for Gedatolisib in PIK3CA Wild-Type Breast Cancer

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The rolling submission is supported by data from the PIK3CA wild-type cohort of the phase 3 VIKTORIA-1 trial evaluating gedatolisib in advanced breast cancer.

Topline data from the phase 3 trial revealed that the gedatolisib-based triplet reduced the risk of disease progression or death by 76% vs fulvestrant alone.

Topline data from the phase 3 trial revealed that the gedatolisib-based triplet reduced the risk of disease progression or death by 76% vs fulvestrant alone.

The FDA has agreed to accept a new drug application (NDA) for gedatolisib (PF-05212384) for the treatment of PIK3CA wild-type hormone receptor (HR)–positive/HER2-negative advanced breast cancer under the agency’s Real-Time Oncology Review (RTOR) program, according to a news release from the drug’s developer, Celcuity Inc.1

Completion of the NDA is slated for the fourth quarter of 2025, based on topline data from the PIK3CA wild-type cohort of the phase 3 VIKTORIA-1 trial (NCT05501886). The trial evaluated the investigational therapy and fulvestrant (Faslodex) with or without palbociclib (Ibrance) in patients with advanced or metastatic HR-positive/HER2-negative advanced breast cancer. Developers aim to complete the NDA submission by the fourth quarter of 2025.

Topline data from the phase 3 trial revealed that the gedatolisib-based triplet reduced the risk of disease progression or death by 76% vs fulvestrant alone. The median progression-free survival (PFS) was 9.3 months vs 2.0 months with fulvestrant, for a difference of 7.3 months. Additionally, gedatolisib/fulvestrant reduced the risk of disease progression or death by 67% vs fulvestrant alone, with respective PFS values of 7.4 months vs 2.0 months, a difference of 5.4 months.

“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, chief executive officer and co-founder of Celcuity, said in the news release.1 “Gedatolisib previously received both breakthrough therapy and fast track designations based on our promising preliminary clinical data. The FDA’s decision further highlights the urgent need for more efficacious therapies than those currently available for patients with HR-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.”

The phase 3 trial enrolled patients with histologically or cytologically confirmed metastatic or locally advanced breast cancer, with a confirmed diagnosis of ER-positive disease and documented HER2 immunohistochemistry (IHC) negative disease. Patients with PIK3CA mutational status were randomly assigned to receive the gedatolisib-based triplet, fulvestrant/alpelisib, or gedatolisib/fulvestrant.2

In the triplet arm, treatment consisted of 180 mg of intravenous gedatolisib given on days 1, 8, and 15 of each 28-day cycles; 125 mg of oral palbociclib given daily on a 3 weeks on, 1 week off schedule; and 500 mg of fulvestrant given over two 5 mL injections every 2 weeks during days 1 and 15 of cycle 1, and then every 4 weeks starting with day 1 of cycle 2. In the active comparator arm, the same dosing schedule of fulvestrant and 300 mg of daily oral alpelisib in two 150 mg tablets given daily was given to patients.

The primary end point of the trial was PFS. Secondary end points included overall survival, overall response rate, duration of response, quality of life, and safety.

Patients were eligible for enrollment if they had documented radiological disease progression on or after prior treatment, radiologically evaluable disease per RECIST v1.1 criteria, an ECOG performance status of 0 to 1, a life expectancy of at least 3 months, and experienced progression following a prior CDK4/6 inhibitor with a non-steroidal aromatase inhibitor.

Those ineligible for trial enrollment included those with a history of other malignancies other than adequately treated non-melanoma skin cancer; prior treatment with a PI3K inhibitor, a protein kinase B inhibitor, a mechanistic target of rapamycin inhibitor, or chemotherapy/antibody drug conjugates for advanced disease; and those who have received more than 2 lines of endocrine therapy.

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 Inc. August 28, 2025. Accessed August 29, 2025. https://tinyurl.com/5ca5u96u
  2. 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 June 24, 2025. Accessed August 28, 2025. https://tinyurl.com/yc3jmmy5

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