Eganelisib/Nivolumab Shows Encouraging Efficacy in Advanced, Metastatic Urothelial Carcinoma

Eganelisib (IPI-549), an investigational PI3K-gamma inhibitor in combination with nivolumab (Opdivo) demonstrated promising efficacy compared with nivolumab alone as treatment of platinum-refractory, immunotherapy naïve patients with advanced metastatic urothelial cancer (mUC), according to updated findings from the phase 2 MARIO-275 clinical trial (NCT03980041), announced the developer, Infinity Pharmaceutical, in a press release.

Full data from the trial will be presented at a medical conference in the first quarter of 2021, according to the developer. The results shared will be based on a pool of 49 patients with MUC treated with eganelisib plus nivolumab or nivolumab monotherapy.

“The combination was well tolerated at the 30 mg dose of eganelisib and provided patient benefit relative to the placebo-controlled arm on important response rate and progression-free survival measures, particularly in urothelial cancer patients with low levels of PD-L1 expression who respond poorly to checkpoint inhibitors alone. We are leveraging the clinical and translational learnings from MARIO-275 in planning a new, registration-enabling study of eganelisib in patients with advanced urothelial cancer,” explained, Adelene Perkins, chief executive officer and chair of Infinity Pharmaceuticals, in a statement.

Perkins also announced plans to share the MARIO-275 trial results with regulatory authorities.

MARIO-275 is a global, phase 2, randomized trial. The 160 patients in the ongoing study are randomized 2:1 to receive eganelisib with nivolumab or nivolumab alone for 28-day cycles. The primary end point of the trial is the objective response rate. The study is also evaluating time to response, duration of response, and progression-free survival, as the key secondary end points.

Eligible patients for enrollment include those histologically or cytologically confirmed urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra, measurable disease per RECIST version 1.1, and disease progression or recurrence after treatment. Patients are required to have had at least 1 prior platinum-based chemotherapy regimen for advanced or metastatic disease. Those enrolled are also required to have disease recurrence within disease recurrence within 1 year of completing a platinum-based neoadjuvant or adjuvant therapy. The ECOG performance status requirement for patients was ≤1.

Patients are excluded from the study due to active brain metastases or leptomeningeal metastases, a serious or uncontrolled medical disorder that may interfere with study treatment, and other conditions.

The combination of eganelisib and nivolumab received Fast Track designation from the FDA in March 2020 to advance the development of the combination. Regarding the study, Perkins stated, “The MARIO-275 study provided Infinity with important insights to shape the future of eganelisib in urothelial cancer.”

_Reference:

_{Infinity Pharmaceuticals provides update for eganelisib in patients with metastatic urothelial cancer. News release. Infinity Pharmaceuticals. January 6, 2020. Accessed January 7, 2020. https://bit.ly/39eapBE}