Bristol-Myers Squibb Company and Infinity Pharmaceuticals have entered a clinical trial collaboration to evaluate the PD-1 inhibitor Opdivo (nivolumab) in combination with the PI3K-gamma inhibitor IPI-549 in patients with advanced solid tumors. The clinical trial (NCT02637531) is recruiting participants now.
The first-in-human, dose-escalation Phase 1/1b clinical trial is evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of IPI-549 alone or in combination with Opdivo in 175 patients with advanced solid tumors, including non-small cell lung cancer (NSCLC), melanoma and squamous cell carcinoma of the head and neck (SCCHN).
IPI-549 is an investigational immunotherapy that selectively inhibits PI3K-gamma. In preclinical studies, IPI-549 was shown to boost the effects of checkpoint inhibitors and to inhibit immunosuppressive macrophages within the tumor microenvironment. This contrasts with what is seen with other immunotherapies, such as immune checkpoint inhibitors, that target immune effector cell function more directly.
Opdivo is designed to overcome immune suppression, by blocking the PD-1/PD-L1 immune checkpoint. It is approved in 50 countries worldwide to treat patients with metastatic non-small cell lung cancer (NSCLC), whose disease progressed during or following platinum-based chemotherapy.
The dose-escalation portion of the trial, examining IPI-549 alone, is ongoing, and the first dose-escalation cohort evaluating IPI-549 in combination with Opdivo, is expected to begin in the next few months This later phase will examine the potential of the combo treatment in driving improved and sustained efficacy and tolerability, compared to current standard of care, by targeting the immunosuppressive 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,” Fouad Namouni, MD, head of oncology development, Bristol-Myers Squibb, said in a press release. “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,” said 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,” said Adams.
Upon completion of the dose-escalation phase of Opdivo in combination with IPI-549, an expansion phase is expected to examine the combination treatment in patients with selected solid tumors.