MINNEAPOLIS, Minnesota, USA , June 2, 2026
Celcuity has announced groundbreaking results from the Phase 3 VIKTORIA-1 clinical trial, demonstrating that its investigational therapy gedatolisib, when combined with fulvestrant with or without palbociclib, significantly improved outcomes for patients with HR-positive, HER2-negative, PIK3CA-mutated advanced breast cancer. Presented in a late-breaking oral session at the 2026 ASCO Annual Meeting, the study revealed that both gedatolisib-based regimens reduced the risk of disease progression or death by approximately 50% compared with the currently approved combination of alpelisib and fulvestrant. The findings position gedatolisib as a potential new standard of care for patients whose disease has progressed after treatment with CDK4/6 inhibitors and aromatase inhibitors, an area where effective therapeutic options remain limited. The pivotal trial marks the first Phase 3 study to demonstrate superiority of one PI3K/AKT/mTOR (PAM) pathway inhibitor over another in advanced breast cancer.
Phase 3 VIKTORIA-1 Trial Delivers Landmark Efficacy Results
The Phase 3 trial evaluated gedatolisib, a novel pan-PI3K/mTORC1/2 inhibitor, in patients with hormone receptor-positive, HER2-negative advanced breast cancer carrying PIK3CA mutations. Results showed that the gedatolisib-triplet regimen consisting of gedatolisib, fulvestrant, and palbociclib reduced the risk of disease progression or death by 50%, achieving a median progression-free survival (PFS) of 11.1 months compared with 5.6 months for patients receiving alpelisib plus fulvestrant. Similarly, the gedatolisib-doublet regimen achieved a median PFS of 11.3 months, representing a 49% reduction in disease progression risk.
The study also demonstrated substantial improvements in objective response rates and duration of response. The triplet regimen achieved an objective response rate of 48.9%, while the doublet delivered a response rate of 35.7%, both outperforming the comparator arm. These outcomes represent some of the strongest efficacy results reported in second-line HR-positive, HER2-negative advanced breast cancer clinical trials.
Multi-Target PAM Inhibition Shows Clinical Advantage
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Researchers believe gedatolisib’s success stems from its unique mechanism of action. Unlike currently approved therapies that target only a single component of the PAM pathway, gedatolisib simultaneously inhibits all four Class I PI3K isoforms, mTORC1, and mTORC2, providing more comprehensive pathway suppression. Resistance to endocrine therapy and CDK4/6 inhibitors remains a significant challenge in advanced breast cancer treatment, and activation of the PAM pathway is a major driver of disease progression. By targeting multiple signaling nodes simultaneously, gedatolisib is designed to overcome adaptive resistance mechanisms that often limit the effectiveness of single-target therapies.
Investigators noted that the Phase 3 VIKTORIA-1 trial established several important milestones, including the highest reported progression-free survival and objective response rate achieved by any Phase 3 endocrine-based regimen in this patient population. These findings reinforce the potential value of broad PAM pathway inhibition as a strategy for improving long-term disease control.
Favorable Safety Profile Supports Regulatory Path Forward
In addition to delivering strong efficacy, gedatolisib demonstrated a favorable safety and tolerability profile. Treatment discontinuation rates due to adverse events remained low, with fewer patients discontinuing therapy compared with those receiving alpelisib and fulvestrant. Investigators reported relatively low rates of severe hyperglycemia and rash, adverse events commonly associated with single-target PI3K inhibitors. Celcuity indicated that the data will support a planned supplemental New Drug Application (sNDA) submission to the U.S. Food and Drug Administration and regulatory filings in other global markets. The company is already preparing for potential commercialization, with an FDA decision on a separate gedatolisib application in advanced breast cancer expected later in 2026.
If approved, gedatolisib could become a transformative treatment option for patients with HR-positive, HER2-negative advanced breast cancer, offering both superior efficacy and improved tolerability compared with existing targeted therapies. The VIKTORIA-1 results further strengthen the growing clinical evidence supporting comprehensive PAM pathway inhibition as a next-generation strategy in precision oncology.
Source: Celcuity press release
