NCI Clinical and Translational Exploratory/Developmental Studies (R21 Clinical Trial Optional)

The NCI Clinical and Translational Exploratory/Developmental Studies (R21 Clinical Trial Optional) grant opportunity is administered by the National Cancer Institute (NCI), which is a component of the National Institutes of Health (NIH) under the U.S. Department of Health and Human Services. This funding opportunity, designated as PAR-25-139, represents a reissue of PAR-22-216 and is designed to support innovative, hypothesis-driven exploratory and developmental cancer research. It aligns with updated NIH agency priorities as of March 31, 2025, and encourages applications that address key issues in cancer treatment, diagnosis, prevention, symptom management, and the reduction of cancer disparities. The primary aim of this grant is to facilitate early-phase clinical and preclinical studies, including comparative oncology and correlative biomarker research, that may involve considerable scientific risk but hold the potential for significant breakthroughs. Eligible studies may include new molecular agents, repurposed treatments, novel combinations, innovative diagnostics, and biomarker validation. Special consideration is given to research exploring therapeutic responses among diverse populations, including age, sex, racial/ethnic, and health disparity groups, as well as comparative studies in dogs that parallel human cancer. This funding opportunity excludes studies focused on basic cancer biology, phase III clinical trials, early-stage biomarker discovery using only in vitro systems, epidemiological research, behavioral interventions, and risk assessment studies. Proposals must reflect distinct and novel approaches not appropriate for the R01 mechanism and are encouraged to build upon existing basic science to transition discoveries into applied preclinical or clinical applications. Eligible applicants include a wide range of U.S. and foreign entities, such as higher education institutions, nonprofit and for-profit organizations, local and state governments, tribal entities, and other public agencies. Applicants must complete several registrations, including SAM, Grants.gov, eRA Commons, and others, to be eligible to apply. There is no cost-sharing requirement, and organizations may submit multiple distinct applications. Applications are accepted electronically through ASSIST, Grants.gov Workspace, or institutional system-to-system platforms. The application process adheres strictly to NIH guidelines and includes required elements such as a detailed protocol synopsis, human subject protections, statistical design, and milestones for clinical trials if applicable. Evaluation is based on overall impact, significance and innovation, rigor and feasibility, and investigator expertise and resources. Applications must be submitted by 5:00 PM local time on specified dates (e.g., February 13 and June 16, 2025), with final submissions due by September 8, 2025. Reviews and awards are made following NIH's peer review process, with decisions based on scientific merit, alignment with program priorities, and funding availability. For questions, applicants can contact several NCI representatives depending on their research area, including Morgan O'Hayre for preclinical studies, Anita Undale for clinical studies, Marjorie Perloff for prevention and symptom management, and Tiffany Wallace for cancer disparities. Additional support is available through the NIH's eRA and Grants.gov helpdesks.