Gedatolisib Triplet Boosts Progression-Free Survival in Breast Cancer

Gedatolisib combo improved PFS in patients with advanced breast cancer after prior therapies: © stock.adobe.com.

Gedatolisib, when combined with Faslodex (fulvestrant) and Ibrance (palbociclib), led to a statistically significant and clinically meaningful improvement in progression-free survival for patients with HR-positive, HER2-negative, PIK3CA wild-type, locally advanced or metastatic breast cancer. This was observed in patients whose disease had progressed on or after treatment with a CDK4/6 inhibitor and an aromatase inhibitor. The benefit of this combination was seen compared to gedatolisib and Faslodex alone, according to a press release from Celcuity.

“Patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer whose disease has progressed while on, or after, treatment with a CDK4/6 inhibitor typically derive limited benefit from subsequent endocrine-based therapy,” Dr. Sara Hurvitz stated in the news release. “The topline data for both gedatolisib regimens from VIKTORIA-1 are potentially practice-changing. To my knowledge, we have not seen Phase 3 results in patients with HR-positive, HER2-negative advanced breast cancer before where there was a quadrupling of the likelihood of survival without disease progression relative to the study control.”

Dr. Hurvitz is the senior vice president of the Clinical Research Division at Fred Hutchinson Cancer Center, Professor and Head of the Division of Hematology and Oncology at the University of Washington, Department of Medicine, and a co-principal investigator for the trial.

In the trial, both gedatolisib-based regimens demonstrated statistically significant and clinically meaningful improvements in progression-free survival (PFS) compared with Faslodex alone. The triplet combination of gedatolisib, Ibrance, and Faslodex reduced the risk of disease progression or death by 76% and achieved a median PFS of 9.3 months, compared with 2 months for Faslodex alone. The doublet regimen of gedatolisib plus Faslodex showed a 67% reduction in the risk of progression or death, with a median PFS of 7.4 months versus 2 months with Faslodex.

The gedatolisib triplet and doublet regimens showed more favorable outcomes than previously observed in a Phase 3 trial for patients with HR-positive, HER2-negative advanced breast cancer. Compared with Faslodex alone, the triplet extended median progression-free survival by 7.3 months and the doublet by 5.4 months—both larger gains than previously reported in this setting. Gedatolisib is also the first treatment targeting the PI3K/AKT/mTOR pathway to demonstrate positive Phase 3 results in patients whose disease progressed on or after a CDK4/6 inhibitor and who have PIK3CA wild-type tumors.

“The topline data from VIKTORIA-1 demonstrate the potential for gedatolisib to become a transformative new medicine for the treatment of patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer whose disease progressed on or after treatment with CDK4/6 inhibitors,” Dr. Igor Gorbatchevsky, chief medical officer of Celcuity, said in the news release. “The 7.3 and 5.4-month incremental improvement in median PFS relative to Faslodex for the gedatolisib regimens are potentially paradigm-shifting results. We are also very excited that treatment with gedatolisib combined with Faslodex with or without Ibrance was well-tolerated by the VIKTORIA-1 patients, and that only a few patients discontinued treatment due to a side effect.”

Fewer patients stopped treatment due to side effects with the gedatolisib triplet and doublet than in the earlier Phase 1b trial or in any Phase 3 trials of currently approved drug combinations for HR-positive, HER2-negative advanced breast cancer. These combinations were also better tolerated than in the Phase 1b trial, with lower rates of hyperglycemia and mouth sores.

Full results from the PIK3CA wild-type group in the VIKTORIA-1 trial will be shared at a medical conference later this year. Celcuity plans to file for Food and Drug Administration approval of gedatolisib in late 2025. Initial findings from the PIK3CA mutation group are also expected by year’s end.

Reference

1. “Celcuity Announces Clinically Meaningful Improvement in Both Progression-Free Survival (“PFS”) Primary Endpoints from PIK3CA Wild-Type Cohort of Phase 3 VIKTORIA-1 Trial.” Celcuity. News Release. July 28, 2025.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.