Celcuity (CELC) Study result summary

Study design and background

• VIKTORIA-1 is a global, randomized, open-label phase III trial evaluating gedatolisib-based regimens (triplet and doublet) versus alpelisib plus fulvestrant in HR-positive/HER2-negative, PIK3CA-mutant advanced breast cancer after progression on CDK4/6 and aromatase inhibitors.

• 362 patients were randomized 3:1:3 to gedatolisib + palbociclib + fulvestrant, gedatolisib + fulvestrant, or alpelisib + fulvestrant, with balanced baseline characteristics and a high proportion of visceral metastases.

• Key eligibility included measurable disease, ≤2 prior lines of endocrine therapy, and no prior mTOR/PI3K/AKT inhibitors or chemotherapy for advanced disease.

• Patients were assigned to cohorts based on PIK3CA mutation status, with Study 2 focusing on PIK3CA-mutated disease.

• Gedatolisib is a multi-target PAM inhibitor, blocking all class I PI3K isoforms, mTORC1, and mTORC2, differentiating it from single-target inhibitors.

Efficacy results

• Gedatolisib triplet and doublet regimens significantly improved median progression-free survival (11.1 and 11.3 months) versus alpelisib plus fulvestrant (5.6 months), with hazard ratios of 0.50 (triplet) and 0.51 (doublet).

• Objective response rates were 49% (triplet) and 36% (doublet), the highest reported for any phase III regimen in this setting.

• Median duration of response was 15.7 months (triplet) and 24.2 months (doublet), both longer than with alpelisib plus fulvestrant.

• Subgroup analyses confirmed consistent benefit across all patient subgroups, including age, menopause status, visceral metastasis, and prior therapies.

• Overall survival trends were promising but data were immature at analysis time.

Safety and tolerability

• Most adverse events with gedatolisib regimens were grade 1 or 2; hyperglycemia and diarrhea rates were notably lower than with alpelisib.

• Stomatitis was the most common treatment-related adverse event, with higher rates in the triplet due to palbociclib.

• Discontinuation rates due to adverse events were lower for gedatolisib regimens (2.6% triplet, 3.8% doublet) than for alpelisib plus fulvestrant (7.1%).

• Most common Grade 3+ adverse events for the triplet included neutropenia (58.8%), stomatitis (16.3%), rash (6.5%), and hyperglycemia (2.6%).

• No new safety signals emerged, and the safety profile was consistent with prior studies.