공시 • Jun 03
Celcuity Announces Detailed Efficacy and Safety Results from the PIK3CA Mutant Cohort of the Phase 3 Viktoria-1 Clinical Trial of Gedatolisib
Celcuity announced detailed efficacy and safety results from the PIK3CA mutant cohort of the Phase 3 VIKTORIA-1 clinical trial of gedatolisib, an investigational pan-PI3K/mTORC1/2 inhibitor, in adults with hormone receptor positive, human epidermal growth factor receptor 2 negative, PIK3CA mutated, locally advanced or metastatic breast cancer, following progression on, or after, treatment with a CDK4/6 inhibitor and an aromatase inhibitor. Gedatolisib plus fulvestrant and palbociclib (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. Gedatolisib plus fulvestrant (the “gedatolisib-doublet”) reduced the risk of disease progression or death by 49% vs. alpelisib plus fulvestrant (HR=0.51; 95% CI: 0.33–0.79; descriptive p=0.0013). Median PFS was 11.3 months with the gedatolisib-doublet versus 5.6 months with alpelisib plus fulvestrant. Gedatolisib regimens demonstrated robust and durable responses: 48.9% objective response rate (“ORR”) and median duration of response (“DoR”) of 15.7 months for the gedatolisib-triplet and 35.7% ORR and median DoR of 24.2 months for the gedatolisib-doublet. The safety data and study treatment discontinuation rates for the gedatolisib-triplet and -doublet were consistent with previously reported data from the PIK3CA wild-type cohort of VIKTORIA-1. The gedatolisib-triplet and -doublet were generally well tolerated in the trial with mostly low-grade treatment-related adverse events (“TRAEs”). The most common Grade 3+ TRAEs for the gedatolisib-triplet, the gedatolisib-doublet, and alpelisib plus fulvestrant groups included neutropenia (58.8%, 0%, and 0.7% of patients, respectively); stomatitis (16.3%, 5.8%, and 5.3% of patients, respectively); rash (6.5%, 5.8%, and 15.1% of patients, respectively); and hyperglycemia (2.6%, 0%, and 14.5% of patients, respectively). TRAEs led to the discontinuation of study treatment in 2.6% of patients in the gedatolisib-triplet group, 3.8% in the gedatolisib-doublet group, and 7.1% in the alpelisib plus fulvestrant group. One Grade 5 TRAE in the gedatolisib-triplet group, which was related to palbociclib, was reported, no Grade 5 TRAEs were reported in the gedatolisib-doublet group, and two Grade 5 TRAEs were reported in the alpelisib plus fulvestrant group. Overall survival, a key secondary endpoint in VIKTORIA-1, while immature at the time of the analysis, showed promising trends for both the gedatolisib-triplet and -doublet. Celcuity intends to submit these data to the U.S. Food and Drug Administration as a supplemental New Drug Application and to submit VIKTORIA-1 data to other regulatory authorities following the sNDA submission. The FDA has granted Priority Review of Celcuity’s New Drug Application for gedatolisib in patients with HR+/HER2-/PIK3CA wild-type ABC and assigned a Prescription Drug User Fee Act goal date of July 17, 2026. VIKTORIA-1 is a Phase 3 open-label, randomized clinical trial to evaluate the efficacy and safety of gedatolisib in combination with fulvestrant, with or without palbociclib, in adults with HR+/HER2- ABC whose disease progressed on or after prior CDK4/6 therapy in combination with an aromatase inhibitor. The trial enrolled 701 subjects regardless of PIK3CA status while enabling separate evaluation of subjects according to their PIK3CA status. For the PIK3CA MT cohort, 350 subjects who met eligibility criteria and had confirmed PIK3CA mutations were randomly assigned (3:3:1) to receive a regimen of either the gedatolisib-triplet, alpelisib and fulvestrant, or the gedatolisib-doublet. Gedatolisib is an investigational, multi-target PAM inhibitor that potently targets all four class I PI3K isoforms, mTORC1, and mTORC2 to induce comprehensive blockade of the PAM pathway. As a multi-target PAM inhibitor, gedatolisib’s mechanism of action is highly differentiated from currently approved single-target inhibitors of the PAM pathway. Inhibition of only a single PAM component gives tumors an escape mechanism through cross-activation of the uninhibited targets. Gedatolisib’s comprehensive PAM pathway inhibition ensures full suppression of PAM activity by eliminating adaptive resistance cross-activation that occurs with single-target inhibitors. Unlike single-target inhibitors of the PAM pathway, gedatolisib has demonstrated equal potency and comparable cytotoxicity in PIK3CA-mutant and -wild-type breast tumor cells in nonclinical studies and early clinical data.