Bristol-Myers Squibb Company and Infinity Pharmaceuticals, Inc. announced a clinical trial collaboration to evaluate Bristol-Myers Squibb’s Opdivo in combination with Infinity’s IPI-549 in patients with advanced solid tumours. The dose-escalation portion exploring IPI-549 as a monotherapy in Infinity’s phase 1 study is continuing, and the first dose-escalation cohort studying IPI-549 in combination with Opdivo, a PD-1 immune checkpoint inhibitor, is expected to begin this fall.

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.

Preclinical data suggest that IPI-549 may enhance the effects of checkpoint inhibitors and may also reverse tumour resistance to checkpoint inhibitors by targeting immune cells and altering the immune-suppressive microenvironment, promoting an anti-tumour immune response. Opdivo is designed to overcome immune suppression. The combination phase of this ongoing Phase 1 study in patients with advanced solid tumours will explore the potential of combining these two agents to drive improved and sustained efficacy and tolerability above the current standard of care by targeting the immune-suppressive cells in the tumour microenvironment.

“Targeting the tumour microenvironment is an important part of our Immuno-Oncology strategy as we continue to advance research for cancers with limited treatment options,” stated Fouad Namouni, M.D., Head of Oncology Development, Bristol-Myers Squibb. “Our agreement with Infinity builds on our continued focus to bring forward potential novel combination treatment options for patients with cancer.”

“We are excited to explore the potential clinical benefits of combining IPI-549 with Opdivo in the next phase of our ongoing Phase 1 study, which is expected to begin this fall,” stated Julian Adams, president of research and development at Infinity. “Our preclinical research demonstrates that IPI-549 may enhance the effects of and reverse tumour resistance to checkpoint inhibitors, providing a strong rationale for evaluating this combination in patients with advanced forms of solid tumours.”

The ongoing phase 1 clinical study of IPI-549 is designed to explore the activity, safety, tolerability, pharmacokinetics and pharmacodynamics of IPI-549 as a monotherapy and in combination with Opdivo in approximately 175 patients with advanced solid tumours. Once the dose-escalation phase evaluating Opdivo plus IPI-549 is completed, an expansion phase is planned to evaluate the combination in patients with selected solid tumours, including non-small cell lung cancer (NSCLC), melanoma and squamous cell carcinoma of the head and neck (SCCHN).

Although there has been great progress in the treatment of cancer, there remains a need for additional treatment options. NSCLC, melanoma and SCCHN, which will comprise three of the expansion cohorts in this Phase 1 study, account for more than 17 percent of all new cancer cases in the US.

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.

IPI-549 is an investigational, orally administered immuno-oncology development candidate that is designed to selectively inhibit PI3K-gamma. In preclinical studies, IPI-549 inhibited immune suppressive macrophages within the tumour microenvironment, whereas other immunotherapies such as checkpoint modulators more directly target immune effector cell function. As such, IPI-549 represents a potentially complementary approach to restoring anti-tumour immunity in combination with other immunotherapies such as checkpoint inhibitors. IPI-549 is an investigational compound and its safety and efficacy has not been evaluated by the US Food and Drug Administration or any other health authority.

Cancer cells may exploit “regulatory” pathways, such as checkpoint pathways, to hide from the immune system and shield the tumour from immune attack. Opdivo is a PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 expressed on activated T-cells, and blocks the binding of PD-L1 and PD-L2, preventing the PD-1 pathway’s suppressive signalling on the immune system, including the interference with an anti-tumour immune response.

Opdivo’s broad global development program is based on Bristol-Myers Squibb’s understanding of the biology behind Immuno-Oncology. Our company is at the forefront of researching the potential of Immuno-Oncology to extend survival in hard-to-treat cancers. This scientific expertise serves as the basis for the Opdivo development program, which includes a broad range of phase 3 clinical trials evaluating overall survival as the primary endpoint across a variety of tumor types. The Opdivo trials have also contributed toward the clinical and scientific understanding of the role of biomarkers and how patients may benefit from Opdivo across the continuum of PD-L1 expression. To date, the Opdivo clinical development programmr has enrolled more than 18,000 patients.

Opdivo (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Ltd (Ono), Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Bristol-Myers Squibb and Ono further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.