Precision Approaches in Radiation Synthetic Combinations (PAIRS, R21 Clinical Trial Optional)

The National Cancer Institute (NCI), part of the National Institutes of Health (NIH) under the Department of Health and Human Services, administers the Precision Approaches in Radiation Synthetic Combinations (PAIRS) program through funding opportunity PAR-22-199. This grant opportunity supports R21 exploratory/developmental research grants aimed at developing synthetic combination strategies involving radiation therapy and actionable molecular targets in cancer treatment. The PAIRS initiative is rooted in the broader NIH mission to support biomedical research and aims to leverage context-dependent synthetic vulnerabilities in tumors created through radiation therapy. The PAIRS program seeks innovative approaches to exploit cancer vulnerabilities induced or intensified by radiation therapy, promoting combinations with molecularly targeted agents. These synthetic combinations should demonstrate an enhanced therapeutic index, improving cancer treatment efficacy while minimizing toxicity to normal tissues. The program supports a broad range of research, from preclinical models to early-phase clinical trials, and is agnostic to the radiation modality used, including external beam radiation and radiopharmaceuticals. Eligible research must integrate radiation as a core component of the combination therapy design, with applications that do not meet this criterion deemed non-responsive. Funding under this FOA is limited to a maximum of $275,000 in direct costs over a two-year period, with no more than $200,000 in a single year. The opportunity accepts new and resubmission applications, with optional clinical trial inclusion. Eligibility extends to a wide range of applicants including public and private institutions of higher education, nonprofits, for-profits, government entities, and foreign organizations. Each applicant organization may submit more than one application provided each is scientifically distinct. Applications must be submitted electronically using the NIH ASSIST system, Grants.gov Workspace, or an institutional system-to-system solution. Applicants are required to follow detailed instructions in the SF424 (R&R) Application Guide and provide a Data Management and Sharing Plan. A Letter of Intent is requested 30 days prior to application deadlines but is not mandatory. Applications are subject to peer review by NIH review panels and are evaluated based on significance, innovation, approach, investigator qualifications, and environment. The review process emphasizes the rationale for the synthetic combination design, including choice of cancer type, radiation modality, and targeted agents. Key deadlines follow NIH’s standard due dates, with the earliest open date for submissions being September 16, 2022. The expiration date for this FOA is May 24, 2025. Questions about the FOA can be directed to Dr. Pataje Prasanna (scientific/research), Ms. Julie Hong (Letter of Intent), and Shane Woodward (grants management). Applications are reviewed in a multi-phase process that includes scientific peer review and an advisory council review, with awards issued contingent upon funding availability and merit-based selection.