Development

Celcuity's gedatolisib triplet beats alpelisib in Phase III breast cancer trial

Edited by Robert McTiernan··3 min read

Celcuity (Nasdaq: CELC) reported that gedatolisib combined with fulvestrant and palbociclib met the primary endpoint of the Phase III VIKTORIA-1 trial, producing a statistically significant improvement in progression-free survival over alpelisib plus fulvestrant in patients with PIK3CA-mutant HR+/HER2− advanced breast cancer who had progressed on a CDK4/6 inhibitor and aromatase inhibitor — data that position the pan-PI3K/mTOR inhibitor as a potential challenger to three already-approved agents in a biomarker-defined second-line setting.

The VIKTORIA-1 trial is a Phase III open-label, randomized study enrolling adults with HR+/HER2− advanced breast cancer whose disease progressed on or after prior CDK4/6 therapy combined with an aromatase inhibitor, stratified by PIK3CA status; the PIK3CA mutant cohort assigned patients 3:3:1 to the gedatolisib triplet, alpelisib plus fulvestrant, or the gedatolisib doublet.

The primary efficacy analysis compared the gedatolisib triplet — gedatolisib, fulvestrant, and palbociclib — against alpelisib plus fulvestrant, demonstrating a statistically significant and, by the company's characterization, clinically meaningful improvement in progression-free survival. A secondary comparison of the gedatolisib doublet against alpelisib plus fulvestrant also reached statistical significance for the same endpoint. Specific hazard ratios, confidence intervals, and median PFS values were not disclosed in the topline release; full data will be presented as a late-breaking oral abstract at the 2026 ASCO Annual Meeting on June 2. Both regimens were described as generally well tolerated with no new safety signals identified.

Celcuity is developing gedatolisib under an exclusive license deal with Pfizer signed in 2021, granting full global rights to the molecule to Celcuity.

The competitive context

The results carry weight in a competitive landscape that has become notably crowded since alpelisib's 2019 FDA approval. Three agents targeting the PI3K/AKT/mTOR axis now hold approval in this space: Novartis's alpelisib (Piqray), which inhibits PI3Kα selectively and is paired with fulvestrant; capivasertib (Truqap), an AstraZeneca pan-AKT inhibitor approved in November 2023 alongside fulvestrant for patients with PIK3CA, AKT1, or PTEN alterations; and inavolisib (Itovebi), a Genentech/Roche PI3Kα inhibitor with an additional mutant p110α degradation mechanism, approved in October 2024 as part of a triplet with palbociclib and fulvestrant. Gedatolisib's active comparator in VIKTORIA-1 was alpelisib.

The AllSci BriefSystematic R&D and deal news. Daily.

Gedatolisib's mechanistic premise is that selective inhibition of a single PI3K pathway node leaves tumors with escape routes through cross-activation of uninhibited targets. As a pan-class I PI3K and mTORC1/2 inhibitor, gedatolisib is designed to block the pathway comprehensively, eliminating the adaptive resistance loops that single-target agents may permit. That rationale also underpins its potential activity in PIK3CA wild-type disease — a cohort for which Celcuity has already submitted a New Drug Application, with the FDA having assigned a PDUFA goal date of July 17, 2026 under Priority Review. The PIK3CA mutant topline data reported this week are intended to support a supplemental NDA submission. Cross-trial comparisons between gedatolisib and inavolisib or capivasertib are limited by differences in trial design, patient populations, and the absence of head-to-head data.

The VIKTORIA-1 trial results in the PIK3CA mutant cohort also extend the scope of gedatolisib's potential label beyond what the pending NDA covers. Where the wild-type NDA, if approved, would address patients whose tumors lack PIK3CA mutations, the mutant cohort data — if they support regulatory filing — would cover the approximately 40% of HR+/HER2− advanced breast cancer patients whose tumors carry those mutations. That subset represents a commercially meaningful slice of a disease type that accounts for roughly 70% of all breast cancers globally.

Celcuity said it intends to present the detailed VIKTORIA-1 trial results at the 2026 ASCO Annual Meeting on June 2, with the late-breaking abstract session scheduled for the morning of that date. The company plans to submit the PIK3CA mutant cohort data to the FDA as a supplemental NDA following the ASCO presentation, with subsequent submissions to other regulatory authorities thereafter. The next concrete milestone for the program is the July 17 PDUFA date for the pending wild-type NDA.

This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/

Spot something wrong? Report an issue with this article