Gedatolisib combinations beat alpelisib regimen in PIK3CA-mutant HR-positive breast cancer

Gedatolisib generated statistically significant and clinically meaningful improvements in progression-free survival in combination with fulvestrant and palbociclib, as well as in combination with fulvestrant alone, compared with alpelisib plus fulvestrant in patients with PIK3CA-mutant, hormone receptor-positive, HER2-negative advanced breast cancer, according to topline results from the phase 3 VIKTORIA-1 trial. A supplemental new drug application submission to the FDA is planned on the basis of these data, and additional regulatory submissions internationally are intended.

The primary efficacy analysis of VIKTORIA-1 demonstrated that the gedatolisib triplet achieved a statistically significant improvement in progression-free survival compared with alpelisib plus fulvestrant in patients with PIK3CA-mutant disease. The secondary end point of progression-free survival for the gedatolisib doublet vs alpelisib plus fulvestrant also demonstrated a statistically significant and clinically meaningful improvement in progression-free survival in the gedatolisib arm, although this comparison was not part of the primary hierarchical testing sequence.

VIKTORIA-1 is a phase 3, open-label, randomized clinical trial evaluating the efficacy and safety of gedatolisib in combination with fulvestrant, with or without palbociclib, in adult patients with HR-positive/HER2-negative advanced breast cancer whose disease progressed on or after prior CDK4/6 inhibitor therapy combined with an aromatase inhibitor. The trial enrolled patients regardless of PIK3CA mutation status, with prospectively defined separate cohorts enabling independent analysis by PIK3CA mutation status.

Eligible patients with confirmed PIK3CA mutations were randomly assigned in a 3:3:1 ratio to receive the gedatolisib triplet, alpelisib plus fulvestrant, or the gedatolisib doublet. The trial is fully enrolled. Additional details regarding dosing, cycle length, patient stratification factors, crossover policy, and additional secondary end points, including overall survival and objective response rate, are expected to be disclosed at the time of full data presentation at the 2026 ASCO Annual Meeting.

According to the topline announcement, both the gedatolisib triplet and doublet were described as generally well tolerated, with manageable safety profiles and no new safety signals identified in the cohorts of patients with PIK3CA-mutant disease.

Gedatolisib is an investigational pan-PI3K and mTORC1/2 inhibitor. It is an intravenously administered, ATP-competitive, multi-target inhibitor of the PI3K/AKT/mTOR pathway that blocks all four class I PI3K isoforms plus mTOR.

A separate new drug application for gedatolisib for the treatment of patients with PIK3CA wild-type HR-positive/HER2-negative advanced breast cancer is already under FDA priority review, with a PDUFA goal date of July 17, 2026, based on data from the wild-type cohort of VIKTORIA-1. As Celcuity awaits an FDA approval decision for gedatolisib in HER-positive, HER2-negative, PIK3CA wild-type advanced breast cancer, the company is setting its sights on a supplemental NDA filing based on the top-line readout in a PIK3CA-mutant breast cancer cohort.