Gedatolisib sNDA Submitted to FDA in PIK3CA-Mutant Advanced Breast Cancer

Celcuity Inc has submitted a supplemental new drug application (sNDA) to the FDA for gedatolisib (Revtorpyk) in combination with fulvestrant (Faslodex), with or without palbociclib (Ibrance), for patients with hormone receptor–positive (HR+)/HER2-negative (–), PIK3CA-mutant, locally advanced or metastatic breast cancer whose disease has progressed on or after at least 1 line of endocrine therapy.¹

The application is supported by results from the PIK3CA-mutant cohort of the phase 3 VIKTORIA-1 trial (NCT05501886), an open-label, randomized study comparing gedatolisib plus fulvestrant, with or without palbociclib, with alpelisib (Piqray) plus fulvestrant in patients with HR+/HER2– advanced breast cancer whose disease progressed on or after a CDK4/6 inhibitor plus an aromatase inhibitor.^1,2 The cohort randomly assigned 350 patients with confirmed PIK3CA mutations 3:3:1 to the gedatolisib triplet (gedatolisib plus fulvestrant plus palbociclib), alpelisib plus fulvestrant, or the gedatolisib doublet (gedatolisib plus fulvestrant).¹

Efficacy and Safety Findings

The gedatolisib triplet reduced the risk of disease progression or death by 50% vs alpelisib plus fulvestrant (HR, 0.50; 95% CI, 0.37-0.68; P< .0001), with a median progression-free survival (PFS) of 11.1 months vs 5.6 months. The gedatolisib doublet reduced the risk of progression or death by 49% vs alpelisib plus fulvestrant (HR, 0.51; 95% CI, 0.33-0.79; descriptive P = .0013), with a median PFS of 11.3 months vs 5.6 months. Objective response rate was 49% with the triplet, with a median duration of response of 15.7 months, and 36% with the doublet, with a median duration of response of 24.2 months.1 Safety with both regimens was generally consistent with previously reported findings from the PIK3CA wild-type cohort of VIKTORIA-1.

"This submission allows us to potentially make [gedatolisib] available to all patients with HR+/HER2– locally advanced or metastatic breast cancer, regardless of PIK3CA mutation status. In the PIK3CA mutant cohort of the VIKTORIA-1 trial, [gedatolisib] demonstrated compelling safety and efficacy results. Pending regulatory approval, we believe [gedatolisbi] as the potential to become an important treatment option in this indication,” said Igor Gorbatchevsky, MD, chief medical officer of Celcuity, in a news release.

Prior FDA Approval

Gedatolisib in combination with fulvestrant, with or without palbociclib, was approved by the FDA on July 14, 2026, for patients with HR+/HER2– locally advanced or metastatic breast cancer without a PIK3CA mutation, following progression on or after at least 1 line of endocrine therapy in the metastatic setting. That approval was based on the PIK3CA wild-type cohort of VIKTORIA-1.

About Gedatolisib

Gedatolisib is a kinase inhibitor of class I PI3K isoforms (α, β, δ, γ) and mTOR complexes mTORC1 and mTORC2, resulting in downstream inhibition of multiple effectors, including AKT. It is also in development for first-line treatment of HR+/HER2– advanced breast cancer and for second-line treatment of metastatic castration-resistant prostate cancer.

Clinical Development Programs

VIKTORIA-2 (NCT06757634), an ongoing phase 3 trial, is evaluating gedatolisib plus palbociclib plus fulvestrant as first-line treatment for patients with endocrine-resistant HR+/HER2– advanced breast cancer (study 1) and gedatolisib plus palbociclib plus letrozole as first-line treatment for patients with endocrine-sensitive disease (study 2). A phase 1/2 trial, CELC-G-201 (NCT0619089), evaluating gedatolisib in combination with darolutamide (Nubeqa) in patients with metastatic castration-resistant prostate cancer, is also ongoing.

REFERENCES

1. Celcuity Submits sNDA to FDA for REVTORPYK™ (gedatolisib) for HR+/HER2-, PIK3CA Mutant Locally Advanced or Metastatic Breast Cancer. News release. Celcuity Inc. August 26, 2026. Accessed August 27, 2026. https://tinyurl.com/3j9drec3

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). ClinicalTrials.gov. Accessed August 27, 2026. https://clinicaltrials.gov/study/NCT05501886