Minneapolis, Minnesota, United States, Aug. 26, 2026
Celcuity Inc., a biotechnology company developing targeted therapies for solid tumors, has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) seeking to expand the use of REVTORPYK™ (gedatolisib) to patients with hormone receptor-positive (HR+), HER2-negative, locally advanced or metastatic breast cancer carrying PIK3CA mutations. The application follows positive results from the PIK3CA-mutant cohort of the Phase 3 VIKTORIA-1 clinical trial. REVTORPYK is already FDA-approved in combination with fulvestrant, with or without palbociclib, for adults with HR+/HER2-negative locally advanced or metastatic breast cancer without a detected PIK3CA mutation following progression after at least one line of endocrine therapy in the metastatic setting. The new submission represents an effort to potentially extend the treatment’s availability to a broader patient population, pending FDA review and regulatory approval. Celcuity stated that, if approved for the proposed indication, REVTORPYK could become the first and only therapy for advanced breast cancer with a PIK3CA mutation that inhibits all four Class I PI3K isoforms—α, β, δ and γ—as well as mTORC1 and mTORC2.
Phase 3 Data Support FDA Submission
The sNDA is supported by efficacy and safety findings from the PIK3CA-mutant population in the Phase 3 VIKTORIA-1 trial. In the trial, the combination of REVTORPYK, fulvestrant and palbociclib reduced the risk of disease progression or death by 50% compared with alpelisib plus fulvestrant, with a hazard ratio of 0.50 and a median progression-free survival (PFS) of 11.1 months versus 5.6 months. A two-drug REVTORPYK regimen combining gedatolisib with fulvestrant also reduced the risk of disease progression or death by 49%, with median PFS of 11.3 months compared with 5.6 months for alpelisib plus fulvestrant. The company reported an objective response rate of 49% and median duration of response of 15.7 months for the REVTORPYK triplet, while the doublet produced a 36% objective response rate and median duration of response of 24.2 months. Safety findings for both regimens were generally consistent with previously reported results from the PIK3CA wild-type cohort.
Targeting PI3K and mTOR Pathways
The regulatory submission builds on the mechanism of gedatolisib, a kinase inhibitor designed to simultaneously target Class I PI3K isoforms and mTOR complexes. By inhibiting PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ, mTORC1 and mTORC2, REVTORPYK is intended to produce broad downstream inhibition of signaling effectors including AKT. This mechanism distinguishes gedatolisib from therapies that primarily target individual components of the PI3K/AKT/mTOR signaling pathway. The VIKTORIA-1 Phase 3 trial enrolled 701 participants regardless of PIK3CA mutation status, while allowing separate analysis of patients according to their mutation status. Within the PIK3CA-mutant cohort, 350 eligible participants were randomly assigned among the gedatolisib triplet, alpelisib plus fulvestrant, and gedatolisib doublet treatment groups. The FDA’s decision on the sNDA could determine whether REVTORPYK can be used in patients with PIK3CA-mutated HR+/HER2-negative advanced breast cancer following progression on endocrine therapy. The proposed expansion is clinically relevant because HR+/HER2-negative breast cancer represents the most common breast cancer subtype, accounting for approximately 70% of breast cancers, while approximately 40% of patients within this subtype are reported to carry PIK3CA mutations. Celcuity is also evaluating gedatolisib in additional clinical settings, including first-line HR+/HER2-negative locally advanced or metastatic breast cancer and metastatic castration-resistant prostate cancer. The company continues to advance the VIKTORIA-2 Phase 3 program, while a Phase 1/2 study is evaluating gedatolisib in combination with darolutamide in metastatic castration-resistant prostate cancer.
Advertisement
Source: Celcuity press relese
