Gedatolisib Combination Improves PFS in PIK3CA-Mutant HR+/HER2- Breast Cancer Versus Alpelisib

Patients with HR+/HER2- metastatic breast cancer who carry the PIK3CA mutation may soon have a more effective treatment option, following an announcement by Celcuity Inc. Topline results from the Phase 3 VIKTORIA-1 clinical trial show that the investigational drug gedatolisib, when used with fulvestrant (Faslodex) and palbociclib (Ibrance), significantly improved progression-free survival (PFS) for those whose cancer progressed after previous hormone therapies, according to a news release issued by the company.

These findings, which could signal a major shift in how doctors treat advanced breast cancer in the second-line setting, will be presented in a late-breaking session at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, taking place May 29 to June 2.

Main data that support the findings

The primary analysis of the VIKTORIA-1 trial found that a "triplet" regimen consisting of gedatolisib combined with fulvestrant and palbociclib led to a statistically significant and clinically meaningful improvement in PFS, a measure of how long a patient lives without their cancer worsening. This triplet therapy was compared directly against a current treatment option, alpelisib (Piqray) combined with fulvestrant.

Additionally, the trial looked at a "doublet" regimen of just gedatolisib and fulvestrant. Although this comparison was a secondary endpoint and not part of the initial primary analysis hierarchy, researchers reported that this doublet also showed a statistically significant and clinically meaningful improvement in PFS when compared to the Piqray and fulvestrant combination.

According to Dr. Sara Hurvitz, co-principal investigator for the trial, patients with this specific mutation often see only modest benefits from therapies that target only a single part of the PI3K/AKT/mTOR (PAM) pathway. The VIKTORIA-1 results suggest that gedatolisib’s approach of blocking the entire pathway more comprehensively can improve outcomes more effectively than targeting just one component.

Trial details

The VIKTORIA-1 trial focused on a specific patient population: those with HR+/HER2- advanced or metastatic breast cancer who also have a PIK3CA mutation. To be eligible for the study, patients must have seen their cancer progress while receiving or after receiving treatment with a CDK4/6 inhibitor and an aromatase inhibitor.

HR+/HER2- breast cancer is the most common subtype of the disease, representing approximately 70% of all breast cancer cases. Among these patients, about 40% have the PIK3CA mutation. The trial was designed to see if gedatolisib could address the limitations of existing second-line treatments.

Dr. Igor Gorbatchevsky, Chief Medical Officer of Celcuity, noted that when these results are viewed alongside earlier data from patients without the PIK3CA mutation (the "wild-type" cohort), gedatolisib shows potential to improve the standard of care in the second-line setting for all patients regardless of their mutation status. Based on these findings, Celcuity intends to submit a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) and other global regulatory authorities.

Safety

In terms of patient safety, the researchers reported that both gedatolisib regimens, the triplet and the doublet, were generally well tolerated by the trial participants. The safety profiles were described as manageable, and no new safety signals were identified during the study.

Brian Sullivan, CEO of Celcuity, noted that researchers have spent nearly 20 years trying to develop a drug that can block the PI3K/AKT/mTOR pathway comprehensively without causing levels of toxicity that would be unacceptable for patients. The company believes the VIKTORIA-1 results validate their approach to targeting these pathways while maintaining a manageable safety profile for those living with advanced breast cancer. Currently, the FDA is already reviewing gedatolisib for use in patients without the mutation, with a goal date for that decision set for July 17 2026.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI, reviewed by a human editor, but not independently verified by a medical professional.

Reference

 “Celcuity's Phase 3 VIKTORIA-1 Trial Achieves Primary Endpoint With Clinically Meaningful Improvement in Progression-Free Survival in PIK3CA Mutant Cohort,” news release.