5 November 2018 - - US-based Bristol-Myers Squibb Company (NYSE: BMY) and Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) have forged a clinical trial collaboration to evaluate Bristol-Myers Squibb's Opdivo in combination with Infinity's IPI-549 in patients with advanced urothelial cancer, the companies said.

IPI-549 is an oral immuno-oncology development candidate that is designed to selectively inhibit phosphoinositide-3-kinase -gamma and is the only investigational PI3K-gamma inhibitor in clinical development.

Infinity will operationalize MARIO-275: MAcrophage Reprogramming in Immuno-Oncology, a global, randomised 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 Opdivo2.

In Infinity's MARIO-1 trial, MDSCs were reduced in the majority of patients treated with IPI-549 monotherapy.

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.

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.

Opdivo is a programmed death-1 immune checkpoint inhibitor that is designed to uniquely harness the body's own immune system to help restore anti-tumor immune response.

By harnessing the body's own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo's leading global development program is based on Bristol-Myers Squibb's scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types.

To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union, and Japan.

In October 2015, the company's Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.