Celcuity’s Phase 3 VIKTORIA-1 trial shows gedatolisib-based regimens doubled progression-free survival versus alpelisib in HR+/HER2-, PIK3CA-mutated advanced breast cancer, with superior efficacy, favorable safety, and FDA review underway.
Written By: Sana Khan, BPharm
Reviewed By: Pharmacally Editorial Team
Celcuity reported positive Phase 3 VIKTORIA-1 results showing that gedatolisib-based regimens significantly improved progression-free survival compared with alpelisib plus fulvestrant in patients with hormone receptor-positive (HR+), HER2-negative, PIK3CA-mutated advanced breast cancer whose disease had progressed following treatment with a CDK4/6 inhibitor and an aromatase inhibitor. Presented as a late-breaking study at the 2026 ASCO Annual Meeting, VIKTORIA-1 (NCT05501886) is the first Phase 3 trial to demonstrate superiority of one PI3K/AKT/mTOR (PAM) pathway inhibitor over another in this patient population.
Gedatolisib is an investigational pan-PI3K/mTOR inhibitor that targets all four Class I PI3K isoforms as well as mTORC1 and mTORC2, providing broader pathway inhibition than currently approved single-target PAM inhibitors and potentially limiting resistance mechanisms that drive disease progression.
Study Design and Arms
The open-label Phase 3 trial enrolled 350 patients with PIK3CA-mutated HR+/HER2- advanced or metastatic breast cancer whose disease had progressed on prior CDK4/6 inhibitor therapy. Patients were randomized to receive gedatolisib plus fulvestrant and palbociclib (triplet), gedatolisib plus fulvestrant (doublet), or alpelisib plus fulvestrant.
The study directly compared multi-target PAM pathway inhibition with the current standard PI3K inhibitor-based regimen in this treatment setting.
Efficacy Outcomes
The gedatolisib triplet reduced the risk of disease progression or death by 50% compared with alpelisib plus fulvestrant (HR 0.50; p<0.0001). Median progression-free survival (PFS) reached 11.1 months versus 5.6 months in the control arm. Objective response rates (ORR) were 48.9% versus 26.0%, while median duration of response (DoR) improved to 15.7 months from 7.5 months.
The gedatolisib doublet also demonstrated substantial benefit, reducing the risk of progression or death by 49% (HR 0.51). Median PFS reached 11.3 months, while ORR and median DoR were 35.7% and 24.2 months, respectively.
Investigators noted that the triplet regimen achieved one of the strongest efficacy outcomes reported in a Phase 3 study of second-line HR+/HER2- advanced breast cancer incorporating endocrine therapy.
Safety and Tolerability
Gedatolisib-based regimens maintained a favorable tolerability profile. Treatment discontinuation due to adverse events occurred in 2.6% of patients receiving the triplet regimen and 3.8% receiving the doublet regimen, compared with 7.1% in the alpelisib arm.
The triplet regimen was associated with higher rates of neutropenia, largely attributable to palbociclib, while rates of severe hyperglycemia and rash were lower than those reported with alpelisib plus fulvestrant. Overall survival data remain immature but continue to show encouraging trends across both gedatolisib treatment groups.
Regulatory Outlook
Celcuity plans to submit the VIKTORIA-1 PIK3CA-mutant data to the U.S. Food and Drug Administration as part of a supplemental New Drug Application and pursue additional global regulatory filings.
Separately, the FDA is currently reviewing gedatolisib for HR+/HER2-/PIK3CA wild-type advanced breast cancer, with a Prescription Drug User Fee Act (PDUFA) target action date of July 17, 2026.
The company is also advancing multiple Phase 3 studies evaluating gedatolisib in the first-line setting. If approved, experts believe the therapy could establish a new treatment benchmark for patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer whose disease progresses after CDK4/6 inhibitor therapy. If approved, gedatolisib could redefine second-line standards of care in HR+/HER2- advanced breast cancer globally
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About the Writer
Sana Jamil Khan (LinkedIn) is a B. Pharm graduate with a strong interest in medical writing and scientific communication. Her work focuses on interpreting clinical research, exploring developments in pharmaceutical science, and presenting complex medical information in a clear and accessible manner. She is particularly interested in topics related to human clinical studies, drug safety observations, and emerging therapeutic research.