Gedatolisib (PF-05212384), an investigational pan-PI3K and mTORC1/2 inhibitor, generated statistically significant and clinically meaningful improvements in progression-free survival (PFS) in combination with fulvestrant (Faslodex) and palbociclib (Ibrance), as well as in combination with fulvestrant alone, compared with alpelisib (Piqray) plus fulvestrant in the cohorts of patients with PIK3CA-mutant, hormone receptor (HR)–positive, HER2-negative advanced breast cancer, according to topline results from the phase 3 VIKTORIA-1 trial (NCT05501886).1
A supplemental new drug application (sNDA) submission to the FDA is planned based on these data, and Celcuity, the developer of gedatolisib, intends to pursue additional regulatory submissions internationally.
Data from the primary efficacy analysis of VIKTORIA-1 demonstrated that the gedatolisib triplet significantly improved PFS compared with alpelisib plus fulvestrant in patients with PIK3CA-mutant disease. Data will be presented in full at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. The secondary end point of PFS also showed a statistically significant and clinically meaningful improvement with the gedatolisib doublet vs alpelisib plus fulvestrant, although this comparison was not part of the primary hierarchical testing sequence.
“Patients with PIK3CA-mutant, HR-positive/HER2-negative advanced breast cancer whose disease has progressed [during] or after treatment with a CDK4/6 inhibitor typically derive modest benefit from subsequent therapies that target only PI3Kα or AKT,” Sara A. Hurvitz, MD, senior vice president of the Clinical Research Division and Smith Family Endowed Chair in Women’s Health at Fred Hutch Cancer Center; professor and head of the Division of Hematology and Oncology at the University of Washington School of Medicine; and a coprincipal investigator of VIKTORIA-1. “VIKTORIA-1 represents the first phase 3 study to demonstrate that comprehensively blocking the PI3K/AKT/mTOR, or PAM, pathway can significantly improve outcomes for patients with PIK3CA mutations compared [with] therapies only targeting a single component of this pathway.”
Gedatolisib Clears the Bar in PIK3CA-Mutant Breast Cancer
- The VIKTORIA-1 trial met its primary end point, showing that a gedatolisib-containing triplet generated a statistically significant PFS improvement vs alpelisib plus fulvestrant in patients with PIK3CA-mutant HR-positive/HER2-negative advanced breast cancer, with an sNDA submission to the FDA planned.
- In the trial, both the gedatolisib-based triplet and the gedatolisib-based doublet regimens yielded statistically significant and clinically meaningful PFS improvements vs control, with manageable safety profiles and no new safety signals reported.
- A separate NDA 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.
How was the VIKTORIA-1 trial designed?
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.¹ The trial enrolled patients regardless of PIK3CA mutation status, with prospectively defined separate cohorts enabling independent analysis by PIK3CA mutation status. Notably, results from the PIK3CA wild-type cohort have been previously reported.
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 (OS) and objective response rate (ORR), are expected to be disclosed at the time of full data presentation at ASCO 2026.
What was the safety profile in VIKTORIA-1?
According to the top-line announcement, both the gedatolisib triplet and doublet were generally well tolerated, with manageable safety profiles and no new safety signals identified in patients with PIK3CA-mutant disease.
What is the regulatory history of gedatolisib?
In January 2026, the FDA granted priority review to a new drug application (NDA) seeking the approval of gedatolisib for the treatment of patients with PIK3CA wild-type HR-positive/HER2-negative advanced breast cancer, with a Prescription Drug User Fee Act target action date of July 17, 2026, based on data from the wild-type cohort of VIKTORIA-1.2
What does the future look like for evaluating gedatolisib in solid tumors?
Beyond the planned supplemental NDA submission for the PIK3CA-mutant indication, 2 additional development programs for gedatolisib are ongoing.¹ The phase 3 VIKTORIA-2 trial (NCT06757634) is evaluating gedatolisib plus a CDK4/6 inhibitor and fulvestrant as first-line therapy for patients with endocrine treatment–resistant, HR-positive/HER2-negative advanced breast cancer; this trial is actively enrolling. A separate phase 1/2 trial, CELC-G-201 (NCT06190899), is evaluating gedatolisib in combination with darolutamide (Nubeqa) in patients with metastatic castration-resistant prostate cancer.
References
- Celcuity’s phase 3 VIKTORIA-1 Trial achieves primary end point with clinically meaningful improvement in progression-free survival in PIK3CA mutant cohort. News release. Celcuity Inc. May 1, 2026. Accessed May 4, 2026. https://ir.celcuity.com/news-releases/news-release-details/celcuitys-phase-3-viktoria-1-trial-achieves-primary-endpoint
- Celcuity announces FDA acceptance of new drug application for gedatolisib in HR+/HER2-/PIK3CA wild-type advanced breast cancer. News release. Celcuity Inc. January 20, 2026. Accessed May 4, 2026. https://ir.celcuity.com/news-releases/news-release-details/celcuity-announces-fda-acceptance-new-drug-application
