Key Takeaways:
Key Takeaways:
Celcuity Inc. said its investigational pan-PI3K/mTORC1/2 inhibitor gedatolisib, combined with fulvestrant and palbociclib, doubled the likelihood of survival without disease progression or death compared with Novartis AG's alpelisib plus fulvestrant in patients with PIK3CA-mutant HR+/HER2- advanced breast cancer, according to data from the Phase 3 VIKTORIA-1 trial presented Tuesday at the American Society of Clinical Oncology annual meeting.
"Therapies that target only PI3K-alpha or AKT typically offer modest benefit for patients with PIK3CA mutant HR+/HER2- advanced breast cancer whose disease has progressed while on or after treatment with a CDK4/6 inhibitor," said Sara Hurvitz, MD, senior vice president of the clinical research division at Fred Hutchinson Cancer Center and co-principal investigator for the trial. "By comprehensively blocking the PI3K/AKT/mTOR, or PAM, pathway, gedatolisib combined with fulvestrant, with or without palbociclib, showed it can offer these patients two times the likelihood of survival without disease progression or death relative to a single-target inhibitor of the PAM pathway."
The gedatolisib-triplet achieved a median progression-free survival of 11.1 months by blinded independent central review, compared with 5.6 months for alpelisib plus fulvestrant, representing a hazard ratio of 0.50 (95% CI: 0.37-0.68; p<0.0001). The objective response rate was 48.9% versus 26.0%, and median duration of response reached 15.7 months versus 7.5 months. The gedatolisib-doublet — without palbociclib — showed a median PFS of 11.3 months (HR=0.51; p=0.0013), an ORR of 35.7%, and a median DOR of 24.2 months. VIKTORIA-1 is the first Phase 3 trial to compare two PAM pathway inhibitors head-to-head in this population.
The results position gedatolisib as a potential new standard of care in PIK3CA-mutant advanced breast cancer, a population where single-target PI3K-alpha inhibitors like alpelisib have shown limited efficacy after CDK4/6 inhibitor progression. Celcuity already has Priority Review from the US Food and Drug Administration for its new drug application in the PIK3CA wild-type cohort, with a PDUFA goal date of July 17, 2026. The company plans to submit a supplemental NDA for the PIK3CA mutant indication and launch commercially in anticipation of potential approval in the third quarter of 2026.
Safety profile favored gedatolisib over alpelisib. Grade 3 or higher treatment-related adverse events included neutropenia (58.8% for the triplet, 0% for the doublet, 0.7% for alpelisib), stomatitis (16.3%, 5.8%, 5.3%), rash (6.5%, 5.8%, 15.1%), and hyperglycemia (2.6%, 0%, 14.5%). Treatment-related adverse events led to discontinuation in 2.6% of patients on the gedatolisib-triplet, 3.8% on the doublet, and 7.1% on alpelisib plus fulvestrant. One Grade 5 TRAE occurred in the triplet group related to palbociclib, while two Grade 5 events were reported in the alpelisib arm.
"Both gedatolisib regimens were well-tolerated with few VIKTORIA-1 patients discontinuing treatment due to an adverse event," said Igor Gorbatchevsky, MD, chief medical officer of Celcuity. "These safety results compare very favorably to those from the patient group treated with alpelisib and fulvestrant."
Overall survival data, a key secondary endpoint, remain immature but showed promising trends for both gedatolisib regimens. Celcuity is also running VIKTORIA-2, a Phase 3 trial evaluating gedatolisib combinations as first-line treatment for HR+/HER2- advanced breast cancer, and a Phase 1b/2 trial in metastatic castration-resistant prostate cancer.
"It is rare in oncology for a targeted therapy to offer both improved efficacy and better safety results relative to another drug in its class," said Brian Sullivan, CEO and co-founder of Celcuity. The positive readout pressures Novartis's Piqray (alpelisib) franchise and validates the multi-target PAM inhibition approach in a biomarker-defined population. Investors will watch for the FDA's decision on the wild-type NDA by July 17 and the timing of the sNDA submission for the mutant cohort.
This article is for informational purposes only and does not constitute investment advice.
