Adding eganelisib to nivolumab shows survival benefit in bladder cancer

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.

References

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.