Advancing Cancer Immunotherapy by Mitigating Immune-related Adverse Events (irAEs) (U01 Clinical Trial Not Allowed) | RFA CA 19 044

Opportunity Information: Apply for RFA CA 19 044

The National Institutes of Health (NIH) published this funding opportunity announcement, RFA-CA-19-044, titled "Advancing Cancer Immunotherapy by Mitigating Immune-related Adverse Events (irAEs) (U01 Clinical Trial Not Allowed)." It uses the U01 cooperative agreement mechanism, meaning projects are expected to involve a more collaborative relationship with NIH staff than a typical research grant, with shared scientific stewardship and coordination as the work progresses. The overall purpose is to support research that explains why immune-related adverse events happen during cancer immunotherapy and to develop approaches that lessen, prevent, or better manage these toxicities without undermining anti-tumor benefit. Clinical trials are not allowed under this FOA, so the emphasis is on preclinical, translational, mechanistic, and biomarker-focused studies rather than interventional trials in patients.

Scientifically, the FOA centers on the problem that many effective immunotherapies, particularly those that broadly stimulate immune function, can trigger inflammatory and autoimmune-like complications. These immune-related adverse events can affect multiple organs and can become dose-limiting or force discontinuation of therapy, reducing the number of patients who can safely benefit. NIH is looking for projects that dig into the mechanisms behind immune reactivity versus immune tolerance, and the autoimmune pathways that get inappropriately activated during treatment. The expectation is that a clearer, more detailed map of the origins, triggers, and signaling cascades that lead to irAEs will reveal actionable targets for mitigation strategies, such as pathway-specific interventions, improved therapeutic designs, or monitoring tools that allow earlier detection and safer clinical management.

The announcement highlights several priority research directions. One major theme is mechanistic work on immune tolerance breakdown and the immunologic circuitry that drives inflammation and autoimmunity in the setting of cancer immunotherapy. Another related theme is improving the target specificity of immunotherapeutic reagents so that the immune system is directed more precisely toward tumor antigens and less toward normal tissues, with the goal of reducing or preventing irAEs at the source. A third, strongly encouraged area is the identification of predictive biomarkers that can flag patients at higher risk for developing irAEs. Biomarkers could include molecular, cellular, genomic, proteomic, or immunologic signatures that predict toxicity before treatment begins or very early after initiation. NIH frames this as especially valuable for patient stratification at the start of therapy and for tailoring the intensity and type of clinical monitoring, potentially making immunotherapy safer and more personalized even before new mitigation drugs or redesigns are available.

In terms of what success looks like, the FOA is aiming to move the field beyond describing adverse events toward understanding causality and immune activation pathways. If the supported work meets its goals, it should help establish a deeper understanding of how inflammatory or autoimmune adverse events originate and become amplified during immunotherapy, and why certain regimens or patient factors make these events more likely. That kind of knowledge is intended to directly inform next-generation immunotherapeutic strategies that maintain anti-cancer efficacy while reducing toxicity, and to improve real-world clinical decision-making through better risk prediction and surveillance.

Organizationally, this is a discretionary federal funding opportunity under a cooperative agreement funding instrument, categorized broadly under health-related activities (with CFDA listings including 93.121, 93.353, 93.393, 93.846, 93.847, and 93.855). The source data list an award ceiling of $375,000, and the original closing date was 2019-04-25, indicating this specific solicitation was time-limited. Even so, the structure and priorities are representative of NIH efforts to address immunotherapy safety as a core barrier to broader and more durable patient benefit.

Eligibility is broad across U.S.-based organizations and governmental units. Eligible applicants include state, county, city/township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; nonprofit organizations (both 501(c)(3) and non-501(c)(3), excluding institutions of higher education where applicable); for-profit organizations other than small businesses; small businesses; public housing authorities/Indian housing authorities; and Native American tribal governments (federally recognized) as well as tribal organizations that are not federally recognized. The FOA also explicitly calls out additional eligible categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions.

There are important restrictions on foreign involvement. Non-domestic (non-U.S.) entities and non-domestic components of U.S. organizations are not eligible to apply, and foreign institutions are not eligible applicants. However, "foreign components" are allowed as defined by the NIH Grants Policy Statement, meaning a U.S. applicant may include certain types of well-justified international collaborations or activities within the project while remaining compliant with NIH policy.

Overall, this FOA is designed to accelerate rigorous, mechanistic, and predictive research that tackles a central safety challenge in modern oncology: the inflammatory and autoimmune toxicities that accompany powerful immune-based cancer treatments. By funding teams that can explain the biology of irAEs, improve therapeutic specificity, and deliver validated predictive biomarkers, NIH is aiming to make immunotherapy both more effective and more tolerable, expanding the number of patients who can receive these treatments safely and with better-informed clinical oversight.

• The National Institutes of Health in the education, food and nutrition, health sector is offering a public funding opportunity titled "Advancing Cancer Immunotherapy by Mitigating Immune-related Adverse Events (irAEs) (U01 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.121, 93.353, 93.393, 93.846, 93.847, 93.855.
• This funding opportunity was created on 2019-02-20.
• Applicants must submit their applications by 2019-04-25. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $375,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA CA 19 044

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