Sachin Yende, MD, MS, and Derek Angus, MD, MPH, recently received an R34 planning grant from the National Institutes of Health for a project titled, “Immunotherapy of sepsis using anti-PDL1 antibody.” This planning grant will enable the Primary Investigators to finalize the logistical and design elements of a phase-2, multicenter, randomized trial that will test a novel immunomodulatory therapy, which has been successfully used to treat patients with cancer, in severe sepsis patients.
The project employs a multi-PI model, with Yende, Associate Professor of Critical Care Medicine and Clinical and Translational Sciences and Director of the Clinical Epidemiology Program in the CRISMA Center, and Angus, Chair of the Department of Critical Care Medicine and Directory of the CRISMA Center, joining Richard Hotchkiss, MD, Professor of Anesthesiology, Washington University and the PI of a previous proposal on the topic.
The project is noteworthy in several aspects. It employs an academic-industry collaboration, receiving industry support from Bristol Myers Squibb, Inc. (BMS). A consortium of investigators from the University of Pittsburgh, Washington University, Emory University, Vanderbilt University, University of Florida, and Ohio State University will work alongside investigators from BMS. Phase 1 of the trial will be funded by BMS and the investigators anticipate the National Institutes of Health will fund Phase 2. The study also uses an adaptive trial design, in which enrollment and allocation can be altered during the trial, in effect personalizing the treatments for the patients in the study.
“For years, immunomodulatory therapy for sepsis targeted the exaggerated immune response,” notes Yende. “In contrast, this trial will test a therapy to reverse immunosuppression. The key challenge here is to understand which patients are most likely to benefit from this therapy and personalize it. We hope that the adaptive study design will help us identify biomarker subgroups to target anti-PDL1 therapy while the phase 2 trial is underway.”