Celcuity says its lead drug, the investigational PI3K/mTOR inhibitor gedatolisib, cleared a bar that has tripped up other PI3K-pathway agents: in the PIK3CA-mutant cohort of the Phase 3 VIKTORIA-1 trial, a gedatolisib-based regimen beat the trial’s active comparator, alpelisib (Piqray) plus fulvestrant (Faslodex). One caution up front on how to read the headline result. The winning arm is a three-drug regimen — gedatolisib plus fulvestrant and the CDK4/6 inhibitor palbociclib (Ibrance) — measured against a two-drug comparator, alpelisib plus fulvestrant. It is not a like-for-like, single-agent PI3K-inhibitor head-to-head.
VIKTORIA-1 (NCT05501886) is an open-label, randomized Phase 3 study that enrolled 701 patients with HR+/HER2- advanced breast cancer who had progressed on a CDK4/6 inhibitor plus a non-steroidal aromatase inhibitor. Patients were randomized by PIK3CA mutation status. The primary endpoint is progression-free survival by blinded independent central review under RECIST v1.1; overall survival and overall response rate are secondary. No results are posted to the trial registry as of this writing.
In its May 1 topline release, Celcuity said the gedatolisib triplet showed a “statistically significant and clinically meaningful improvement in progression-free survival” over alpelisib, a PI3Kα inhibitor, plus fulvestrant. A secondary, non-hierarchical comparison of the two-drug gedatolisib doublet (gedatolisib plus fulvestrant) against the alpelisib doublet also showed a statistically significant and clinically meaningful PFS improvement, per the company. Both gedatolisib regimens were “generally well tolerated, with manageable safety profiles, and no new safety signals,” the release said. No adverse-event rates, dose interruptions, or discontinuation data have been released; the tolerability characterization is the company’s and cannot yet be checked against trial data.
The numbers aren’t public yet
What that release did not contain: a hazard ratio, a confidence interval, median PFS for any arm, or the cohort’s patient count. The detailed results are slated for a late-breaking abstract oral session at the 2026 ASCO Annual Meeting in Chicago on June 2, 9:45 a.m. to 12:45 p.m. CDT. Separately, Celcuity is hosting its own management webcast and conference call at 8:00 a.m. EDT the same day to discuss the results.
The headline is real; the effect size is still a press-release adjective, not a number.
For context, this is not a class of drugs that should be read as low-risk. PI3K/AKT/mTOR pathway inhibitors as a group are generally associated with clinically significant toxicities — including hyperglycemia, rash and in some cases severe cutaneous reactions, diarrhea, and stomatitis — and the alpelisib comparator itself carries known serious risks of hyperglycemia and hypersensitivity reactions in its approved use. None of this is treatment guidance, and the VIKTORIA-1 regimens’ actual safety profile cannot be assessed until the trial data are released.
Co-principal investigator Sara Hurvitz, MD, senior vice president of the clinical research division at Fred Hutch Cancer Center, said in the release that patients with PIK3CA-mutant HR+/HER2- advanced breast cancer whose disease progresses on or after a CDK4/6 inhibitor “typically derive modest benefit from subsequent therapies that target only PI3Kα or AKT.” Celcuity says it intends to submit the data to the FDA as a supplemental New Drug Application; a separate July 17, 2026 PDUFA date already stands for gedatolisib in the PIK3CA wild-type cohort. The ASCO data will decide how meaningful the mutant-cohort win is.