Gedatolisib Combination Extends PFS in PIK3CA-Mutant Breast Cancer

The phase 3 VIKTORIA-1 trial (NCT05501886) evaluating gedatolisib in combination with fulvestrant (Faslodex) and palbociclib (Ibrance) has met its primary end point, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients with PIK3CA-mutant breast cancer compared with alpelisib (Piqray) and fulvestrant.¹

The trial results, which focused on patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2–) advanced or metastatic breast cancer, suggest a potential new treatment pathway for patients whose disease has progressed following prior endocrine therapy and cyclin-dependent kinase 4/6 (CDK4/6) inhibitor regimens.

A secondary end point of the study, PFS with a doublet therapy of gedatolisib plus fulvestrant, also demonstrated statistically significant and clinically meaningful improved compared with alpelisib and fulvestrant.

Full data will be presented as a late-breaking abstract at the 2026 ASCO Annual Meeting, taking place May 29 to June 2, 2026, in Chicago, Illinois.

Primary End Point Achievement in PIK3CA-Wild-Type Cohort

The VIKTORIA-1 trial previously reached its primary end point in the cohort of patients with PIK3CA-wild-type (WT) tumors. As published in the Journal of Clinical Oncology in March 2026, the combination of gedatolisib and fulvestrant resulted in a 55% reduction in the risk of disease progression or death compared with fulvestrant monotherapy (HR, 0.45; P <.0001).²

“This [was] the first study to show benefit of a PI3K-inhibitor in [PIK3CA-WT] disease; thus many were pleasantly surprised by these data. A phase 1b study [NCT02684032] showed that gedatolisib combined with palbociclib and [endocrine therapy] produced very promising efficacy in all patients regardless of PIK3CA mutation status. We were happy to see this level of efficacy generated by a randomized phase 3 study in 100% CDK4/6 pretreated patients with advanced disease and PIK3CA-WT disease,” said Sara Hurvitz, MD, senior vice president and director of the Clinical Research Division, professor in the Clinical Research Division, and Smith Family Endowed Chair in Women’s Health at Fred Hutch Cancer Center, in an interview with Targeted Oncology.

Gedatolisib is an investigational, potent, dual mTOR/PI3K inhibitor. By targeting both nodes of the pathway, the agent aims to overcome the primary resistance mechanisms that frequently emerge during treatment with CDK4/6 inhibitors.

Trial Design and Patient Population

The VIKTORIA-1 study is an open-label, randomized phase 3 trial designed to evaluate the efficacy and safety of gedatolisib in combination with fulvestrant, with or without palbociclib (Ibrance). The study enrolled patients with HR+/HER2– advanced breast cancer who experienced disease progression on or after treatment with a CDK4/6 inhibitor in combination with an aromatase inhibitor. Patients were stratified into 3 distinct groups based on their PIK3CA mutation status. ²

Safety and Tolerability

The safety profile of the gedatolisib and fulvestrant regimen was reported to be consistent with observations from previous phase 2 clinical trials.¹ Common adverse events (AEs) associated with the PI3K/mTOR inhibitor class typically include stomatitis, rash, diarrhea, and hyperglycemia. The discontinuation rate due to treatment-related AEs remained low, supporting the feasibility of the dosing schedule in this pretreated patient population.

Clinical Context and Regulatory Status

The management of HR+/HER2– metastatic breast cancer has evolved rapidly with the integration of CDK4/6 inhibitors into first-line and second-line settings. However, nearly all patients eventually develop resistance, necessitating the development of novel targeted therapies.

The new drug application (NDA) of gedatolisib in patients with PIK3CA-WT disease received priority review in January 2026. The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of July 17, 2026.³ Celcuity, trial sponsor, intends to submit a supplemental NDA based on these findings in the PIK3CA-mutant cohort.¹

REFERENCES

1. Celcuity's Phase 3 VIKTORIA-1 Trial Achieves Primary Endpoint With Clinically Meaningful Improvement in Progression-Free Survival in PIK3CA Mutant Cohort. News release. Celcuity Inc. May 1, 2026. Accessed May 4, 2026. https://tinyurl.com/2tfx66pb

2. Hurvitz A, Layman RM, Curigliano G, et al. VIKTORIA-1 Trial of Gedatolisib Plus Fulvestrant With or Without Palbociclib in Hormone Receptor-Positive/HER2‚àí/PIK3CA Wild-Type Advanced Breast Cancer. J Clin Oncol. 44, 1108-1119(2026). DOI:10.1200/JCO-25-02643

3. 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://tinyurl.com/mxzywcxd