Novel Approaches to Support Therapeutic Development in Ultra-Rare Cancers
Can you apply?
This grant is for institutions and organizations developing novel therapeutic approaches for ultra-rare cancers (approximately 300-400 annual U.S. cases or fewer). Eligible applicants include academic research institutions, cancer centers, nonprofits, and industry partners collaborating on drug development. Projects may focus on pediatric and adult cancers, including molecularly-defined subsets of common cancers.
Funded activities include infrastructure for coordination networks and data repositories, investigations of early clinical endpoints, and collaborative multi-stakeholder efforts. Projects should facilitate regulatory decision-making and overcome challenges in ultra-rare cancer drug development.
Geographic scope is national with potential for international collaboration on data sharing.
This grant is for institutions and organizations developing novel therapeutic approaches for ultra-rare cancers (approximately 300-400 annual U.S. cases or fewer). Eligible applicants include academic research institutions, cancer centers, nonprofits, and industry partners collaborating on drug development. Projects may focus on pediatric and adult cancers, including molecularly-defined subsets of common cancers.
Funded activities include infrastructure for coordination networks and data repositories, investigations of early clinical endpoints, and collaborative multi-stakeholder efforts. Projects should facilitate regulatory decision-making and overcome challenges in ultra-rare cancer drug development.
Geographic scope is national with potential for international collaboration on data sharing.
Program description
Background
The FDA Oncology Center of Excellence (OCE) aims to advance the development and regulation of oncology products for patients with cancer. The Pediatric Oncology Program and Rare Cancers Program were established to facilitate and expedite drug development for pediatric and other rare cancers. OCE’s Project Catalyst connects scientific knowledge, creative insight, and medical professionals to foster early-stage product innovation, which is particularly important to address the challenges related to product development for ultra-rare cancers. In collaboration with the National Institutes of Health (NIH) and the OCE, the Foundation for the National Institutes of Health (FNIH) recently launched the design phase of the Ultra-Rare Cancer Treatment Advancement Program (ULTRA), a new public-private partnership dedicated to accelerating the development of innovative ultra-rare cancer treatments.
For the purposes of this NOFO, the FDA OCE refers to cancers with an approximate annual incidence in the U.S. of 300 to 400 people or less as ultra-rare (a more stringent criterion compared to the threshold for a rare disease specified in the Orphan Drug Act based on a U.S. prevalence of <200,000 people).
Many of the challenges involved in drug development for ultra-rare cancers are similar to those for rare diseases and can include:
- Difficulty enrolling sufficient numbers of patients to clinical trials
- Limited financial incentives for drug development
- Insufficient understanding of the cancer pathophysiology, molecular characteristics, and natural history
- Limited or lack of timely access to molecular testing to determine eligibility for treatment with targeted therapies
- Complexities associated with designing clinical trials that are adequate to establish safety and effectiveness
Advancing technologies such as single cell multi-omic analyses have helped define some ultra-rare cancers at the molecular level, providing new opportunities for targeted drug development. Pediatric oncology has several examples of tumor types with known translocation-induced, oncogenic driver fusion proteins. Other examples of ultra-rare cancers defined today by molecular pathology include: neuroectodermal tumors, pulmonary blastoma, desmoplastic small round cell tumor (DSRCT), epithelioid sarcoma, diffuse intrinsic pontine glioma, fibrolamellar carcinoma, and malignant rhabdoid tumors.
Purpose and Research Objectives
The purpose of this NOFO is to support new approaches that can be applied to facilitate therapeutic development in ultra-rare pediatric and adult cancers, including molecularly-defined subsets of more common cancers.
Specific areas of interest include, but are not limited to, the following examples:
- Development of infrastructure for a coordination network and data repository for patient-level data across institutions and internationally to support drug development and regulatory decision-making for one or more ultra-rare cancers.
- Investigations to explore opportunities to develop and validate early clinical endpoints and other novel efficacy endpoints for evaluation of treatments for ultra-rare cancers.
- Development and implementation of a collaborative multi-stakeholder effort to support generation and use of real-world data leveraging a registry framework for use in development of new therapies for pediatric patients with diffuse midline glioma (DMG) (including diffuse intrinsic pontine glioma, DIPG).
- Innovative approaches to identify new biologically-driven opportunities for clinical development of previously approved drugs or biologics (hereafter referred to as drugs), including drugs for which development has been discontinued, in ultra-rare cancers.
- Research to develop novel approaches to preserve the availability of drugs for which commercial developers have discontinued adult development that have strong potential in ultra-rare cancers but lack financial incentives for commercial development
- Development of methods to incorporate use of telemedicine and/or pragmatic trial design elements (e.g., collecting laboratory and/or imaging data from local facilities) for patient assessments to facilitate enrollment of patients with ultra-rare cancers
- Development of nanoparticle-based delivery approaches for therapeutic nucleic acids targeting onco-fusion transcription factors in metastatic tumor animal models using targeted bioPROTAC degradation or genomic editing strategies. Successful efforts should demonstrate effective delivery and expression in-vivo to tumor cells, and downregulation of the target transcription factor protein while minimizing off-target effects and limiting sequestration of the nanoparticle by the liver, spleen, and lungs.
- Research to exhaustively characterize the plasma-membrane protein expression (surfaceome) of an ultra-rare cancer and the presumed healthy tissue of origin, as well as the resident-tissue stem cells, by single-cell transcriptomics and proteomics. These studies, and available correlative database analyses, should be designed to identify possible combinatorial signatures of plasma membrane proteins unique to the ultra-rare tumor. Tumors of interest include Sclerosing epithelioid fibrosarcoma and atypical teratoid rhabdoid tumors (ATRT).
Who can apply
Eligible applicants
- 501(c)(3) Public Charity
- City / Municipal Government
- County Government
- Nonprofits
- Private University
- Public Authority
- Public K-12 School
- Public University
- Small Business (SBA-defined)
- Special District
- State Government
- Tribal Nation
- Tribal Organization
Details
This grant is for institutions and organizations developing novel therapeutic approaches for ultra-rare cancers (approximately 300-400 annual U.S. cases or fewer). Eligible applicants include academic research institutions, cancer centers, nonprofits, and industry partners collaborating on drug development. Projects may focus on pediatric and adult cancers, including molecularly-defined subsets of common cancers.
Funded activities include infrastructure for coordination networks and data repositories, investigations of early clinical endpoints, and collaborative multi-stakeholder efforts. Projects should facilitate regulatory decision-making and overcome challenges in ultra-rare cancer drug development.
Geographic scope is national with potential for international collaboration on data sharing.
How to apply
Application links
Required documents
- Standard federal forms (SF-424, SF-424 Supplement)
- Project Narrative
- Budget and Budget Narrative
- Letters of Commitment from partner institutions
- Data Management and Governance Plan (for network/repository proposals)
- Curriculum Vitae for key personnel
Program contact
- 👤 Patrick Johnson Grantor
- 📧 patrick.johnson@fda.hhs.gov
- 📞 3017960154
Funding track record
Recent awards under CFDA 93.103 from the last 3 years — real organizations that won funding through this same program.
Top 10 Largest Recent Awards
-
$121,795,918
-
$76,105,626
-
$50,217,964
-
$47,940,304
-
$36,000,000
-
$35,573,997
-
$35,391,995
-
$30,732,300
-
$23,332,999
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$21,347,288
Top States by Funding
- AZ 3 awards $131.4M
- MD 7 awards $108.5M
- CA 9 awards $106.5M
- VA 5 awards $96.6M
- PA 10 awards $77.4M
Source: USAspending.gov — federal spending transparency. Data covers last 3 years.
FAQ
What is considered an ultra-rare cancer for this grant?
Cancers with approximately 300-400 or fewer new cases annually in the U.S. This is stricter than the Orphan Drug Act threshold.
What types of projects are funded?
Infrastructure for patient data networks, studies of novel efficacy endpoints, and collaborative multi-stakeholder initiatives supporting therapeutic development.
Is cost sharing required?
No, this grant does not require matching funds or cost sharing from applicants.
What is the funding level and project timeline?
Award amounts reach up to $500,000 from a $1,500,000 pool. Specific project duration is not detailed; contact the FDA OCE for timeline expectations.
Who can be a partner in this collaborative effort?
Institutions, cancer centers, nonprofits, and industry partners can participate in network development and data sharing initiatives.
💡 Tips for applicants
- Focus on addressing one of the five core challenges in ultra-rare cancer development: patient enrollment, financial barriers, pathophysiology understanding, molecular testing access, or clinical trial design.
- Build multi-institutional partnerships early. The FDA values collaboration across academic centers, industry, and international organizations.
- Use molecular characterization data to define your target population precisely. Examples include fusion-driven pediatric tumors and molecularly-defined subsets.
- Emphasize how your infrastructure or approach will benefit regulatory decision-making and accelerate drug development timelines.
- Connect to existing FDA resources like Project Catalyst and the Ultra-Rare Cancer Treatment Advancement Program (ULTRA) to strengthen your proposal.
⚠️ Common mistakes
Defining "ultra-rare" too broadly using Orphan Drug thresholds instead of the stricter 300-400 annual incidence criterion. Proposing research without clear connection to therapeutic development acceleration. Underestimating the complexity of multi-institutional coordination; detailed governance and data-sharing agreements are critical.
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