The NCI Clinical and Translational Exploratory/Developmental Studies (R21 Clinical Trial Optional) is a grant opportunity offered by the National Cancer Institute (NCI), part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH). This Notice of Funding Opportunity (NOFO), identified by the funding number PAR-25-139, is designed to support the development of early-stage, exploratory cancer research projects. This funding mechanism aims to encourage conceptual research that may be high-risk but potentially high-reward, with the capacity to lead to breakthroughs in cancer diagnostics, therapeutics, imaging, and prevention.

The R21 grant mechanism is particularly intended for the early and conceptual phases of research projects. This includes clinical trials in diagnosis, treatment, imaging, symptom and toxicity management, as well as cancer prevention. In addition, the program supports related correlative studies and the development of novel agents, models, radiotherapies, and mechanism-driven combinations. The program also welcomes preclinical studies that utilize clinically relevant models and imaging technologies, especially those with the potential to translate into first-in-human clinical trials. This framework provides a unique opportunity for researchers to pursue innovative research directions that may not yet be ready for larger-scale funding under other mechanisms.

Eligible applicants for this grant span a wide array of entities including state and local governments, public and private higher education institutions, nonprofit organizations, public housing authorities, tribal governments and organizations (both federally recognized and other), school districts, and for-profit organizations including small businesses. Additional eligible institutions include Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Alaska Native and Native Hawaiian Serving Institutions, faith-based and community-based organizations, regional organizations, and non-U.S. entities such as foreign organizations.

Applicants are not required to provide cost sharing or matching funds. The estimated total program funding available is $200,000, with the award ceiling set at $275,000. The closing date for application submission is July 1, 2025, and the opportunity was officially posted on November 4, 2024. While the number of expected awards is not specified, this R21 grant supports discretionary funding, and the availability of funds may influence the number of awards granted.

To apply or learn more, applicants are encouraged to consult the full funding announcement, which is available at https://grants.nih.gov/grants/guide/pa-files/PAR-25-139.html. For assistance with accessing the opportunity or technical issues, applicants can contact NIH Grants Information at grantsinfo@nih.gov. Section VII of the full announcement also includes detailed contact information for programmatic and peer review queries.

This funding opportunity falls under multiple Assistance Listings related to cancer research: 93.393, 93.394, 93.395, 93.396, and 93.399. While it is primarily focused on health and education activities, it is ultimately designed to accelerate cancer research and drive innovation at its most foundational levels.