NEW YORK – Infinity Pharmaceuticals on Thursday said that in a Phase II study the combination of eganelisib and nivolumab (Bristol Myers Squibb's Opdivo) benefitted urothelial cancer patients with PD-L1-negative tumors.
Based on the data from the MARIO-275 trial, the company will conduct a registration-enabling study of its PI3K-gamma inhibitor in urothelial cancer patients with low PD-L1 expression and explore its activity in other tumor types with low PD-L1 expression.
In the MARIO-275 trial, eganelisib plus the checkpoint inhibitor nivolumab was compared to nivolumab and placebo as a second-line treatment for advanced urothelial cancer patients. In the overall population, 30 percent of patients on eganelisib-nivolumab responded compared to 25 percent on nivolumab alone. The complete response rate was 12 percent in the combination arm versus 6 percent in the single-agent arms, and the stable disease rate was 24 percent versus 6 percent, respectively.
However, according to Infinity, the "greatest benefit" of the eganelisib-nivolumab combo was in PD-L1-negative urothelial cancer patients. In this subset, the overall response rate was 26 percent on the combination compared to 14 percent for those on nivolumab alone. Nine percent of patients taking eganelisib in addition to nivolumab achieved a complete response and 30 percent had stable disease. In comparison, none of the patients in the nivolumab monotherapy arm had a complete response or stable disease.
The drug combination also reduced the tumor burden in 58 percent of PD-L1-negative urothelial cancer patients versus 17 percent among those on just nivolumab. Eganelisib also extended median progression-free survival to 9.1 weeks compared to 7.9 weeks when nivolumab was given alone.
"These results, in combination with other efficacy measures, including prolonged progression-free survival, are particularly meaningful given that the PD-L1-low patient population has historically poor overall response rates to checkpoint inhibitors of approximately 16 percent," Brian Schwartz, consulting chief physician at Infinity, said in a statement. "Based on the strength of these data and the magnitude of the unmet need in the PD-L1-low population, we are planning a registration-enabling study in advanced urothelial cancer and also are exploring the potential of eganelisib in PD-L1-low patients more broadly across cancer types."
Boston-based Infinity is also studying eganelisib in combination with Genentech's checkpoint inhibitor atezolizumab (Tecentriq) and chemotherapy in front-line triple-negative breast cancer and in combination with atezolizumab and bevacizumab (Genentech's Avastin) in front-line renal cell carcinoma.