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The addition of the PI3K-gamma inhibitor eganelisib to the PD-1 inhibitor nivolumab (Opdivo) was associated with a 38% reduction in the risk of death compared with nivolumab alone in patients with advanced urothelial carcinoma enrolled in the phase 2 MARIO-275 trial.1
In the overall study population of 49 patients, the median overall survival (OS) was 15.4 months with the combination compared with 7.9 months with nivolumab alone (HR, 0.62). The 1-year OS rates were 59% versus 32%, respectively.
The OS benefit in patients with PD-L1–negative tumors mirrored the benefit in the overall study population. In the PD-L1–negative subset, the median OS was 15.4 months with the combination versus 7.9 months in the control arm (HR, 0.60). The 1-year OS rates in these patients were 54% versus 17%, respectively.
Overall, the global phase 2 MARIO-275 trial (NCT03980041) randomized patients with advanced urothelial carcinoma in a 2:1 ratio to eganelisib /nivolumab (n = 33) or placebo/nivolumab (n = 16). Prior immune checkpoint-inhibitor therapy was not allowed and patients had to have progressed or recurred following treatment with platinum-based chemotherapy. The primary end point of the study was objective response rate (ORR).
Response data from the trial were presented in February at the 2021 Genitourinary Cancers Symposium.2 In the overall population, the ORR was 30% with the combination versus 25% with placebo. The complete response rates and disease control rates were 12% versus 6% and 55% versus 31%, respectively.
Specifically among patients with PD-L1–negative disease, the ORRs were 26% with eganelisib plus nivolumab versus 14% with nivolumab alone. The complete response rates and disease control rates were 9% versus 0% and 57% versus 14%, respectively.
The most frequently reported adverse events (AEs) across all grades in the eganelisib and placebo arms were pyrexia (33% vs 0%, respectively), decreased appetite (30% vs 19%), pruritis (24% vs 6%), asthenia (21% vs 31%), and transaminase elevation (21% vs 6%).2 The most common grade 3 or higher AEs were hepatotoxicity (15% vs 0%, respectively), transaminase elevation (12% vs 6%), and rash (9% vs 0%).
“The promising survival benefit was noted after over a year of following MARIO-275 patients versus the control arm as well as compared to historical trials including CheckMate-275, particularly given the magnitude of the unmet need in second-line urothelial carcinoma, including in the PD-L1–negative patient population,” Brian Schwartz, MD, consulting Chief Physician, Infinity Pharmaceuticals, the developer of eganelisib, stated in a press release.
“We believe OS represents a key registrational endpoint, and given these exciting new OS data, we are exploring the optimal study design for a potential registration study and expect to provide a program update by the end of 2021,” added Schwartz.
1. Infinity Pharmaceuticals Presents Updated Data from Phase 2 MARIO-275 Trial in Urothelial Cancer (UC) and Phase 2 MARIO-3 Trial in Triple Negative Breast Cancer (TNBC). Published online July 27, 2021. Accessed July 28, 2021. https://bwnews.pr/3y6gEmt.
2. Infinity Pharmaceuticals Presents Data from Randomized, Placebo-Controlled, Phase 2 MARIO-275 Trial of Eganelisib and Nivolumab in Advanced Urothelial Cancer at ASCO Genitourinary Cancers Symposium. Published online February 11, 2021. Accessed July 28, 2021. https://bit.ly/3xbIZXk.