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 tumors.
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 tumor resistance to checkpoint inhibitors by targeting immune cells and altering the immune-suppressive microenvironment, promoting an anti-tumor immune response. Opdivo is designed to overcome immune suppression. The combination phase of this ongoing Phase 1 study in patients with advanced solid tumors 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 tumor microenvironment.
“Targeting the tumor 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 tumor resistance to checkpoint inhibitors, providing a strong rationale for evaluating this combination in patients with advanced forms of solid tumors.”
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 tumors. 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 tumors, 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 U.S.
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 tumor 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-tumor 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 U.S. Food and Drug Administration or any other health authority.
(Source: Business Wire)
Filed Under: Drug Discovery
