BMS, Infinity to assess Opdivo-IPI-549 combo in urothelial cancer

Bristol-Myers Squibb Company and Infinity Pharmaceuticals announced a clinical trial collaboration to evaluate Bristol-Myers Squibb’s Opdivo in combination with Infinity’s IPI-549 in patients with advanced urothelial cancer. IPI-549 is an oral immuno-oncology development candidate that is designed to selectively inhibit phosphoinositide-3-kinase (PI3K)-gamma and is the only investigational PI3K-gamma inhibitor in clinical development.

Infinity will operationalize MARIO-275: MAcrophage Reprogramming in Immuno-Oncology, a global, randomized Phase 2 study to evaluate the effect of adding IPI-549 to Opdivo in checkpoint-naïve advanced urothelial cancer patients who have progressed or recurred following treatment with platinum-based chemotherapy. Approximately 150 patients will be randomized between combination therapy and Opdivo monotherapy. The primary endpoint of the trial will be overall response rate, which will be assessed in the overall population as well as in subsets of patients with different baseline levels of myeloid derived suppressor cells (MDSCs). Opdivo is approved for use by the FDA as a single agent in patients with locally advanced or metastatic urothelial cancer who have progressed or recurred following treatment with platinum-based chemotherapy or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. In exploratory analyses of the CheckMate -275 data, high levels of MDSCs were associated with shorter overall survival in patients treated with Opdivo 2. In Infinity’s MARIO-1 trial, MDSCs were reduced in the majority of patients treated with IPI-549 monotherapy.3 IPI-549 in combination with Opdivo has been administered to over 80 patients and demonstrated early evidence of clinical activity with translational studies demonstrating evidence of on-mechanism IPI-549-mediated effects.4

“The expansion of our relationship with Infinity underscores our efforts to follow the science and support potential novel combination therapies in immuno-oncology for cancer patients with limited treatment options,” said Fouad Namouni, M.D., head of Oncology Development, Bristol-Myers Squibb. “Our goal is to determine whether targeting the tumor microenvironment with IPI-549 will enhance the activity of Opdivo for people with urothelial cancer and potentially in other tumor types where MDSCs suppress the immune response.”

“We are excited to advance the development of IPI-549 further into the checkpoint inhibitor treatment-naïve setting with this randomized study in collaboration with the team at Bristol-Myers Squibb.,” said Dr. Sam Agresta, Chief Medical Officer of Infinity. “There continues to be a significant unmet need for additional treatment options for people living with urothelial cancer, and we are excited to evaluate the potential of this combination.”

Infinity is continuing to evaluate IPI-549 in combination with Opdivo in MARIO-1, a Phase 1/1b study in patients with advanced solid tumors.

Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world in July 2014, and currently has regulatory approval in 54 countries including the United States, Japan, and in the European Union.

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