RFA-CA-27-005-Revised-Full-Announcement.html

Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

Note: Not all NIH Institutes, Centers, and Offices (ICOs) participate in Announcements. Applicants should carefully note which ICOs participate in this announcement and view their respective areas of research interest at the ICO-Specific Scientific Interests website. ICOs that do not participate in this announcement will not consider applications for funding.

Funding Opportunity Title

Glioblastoma Therapeutics Network (GTN) (U19 Clinical Trial Required)

Activity Code

U19 Research Program – Cooperative Agreements

Announcement Type

Reissue of

RFA-CA-20-047

Related Notices

Funding Opportunity Number (FON)

RFA-CA-27-005

Companion Notice of Funding Opportunity

None

Number of Applications

Only one application per institution is allowed, as defined in Section III. 3. "Additional Information on Eligibility" See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.394, 93.395

Notice of Funding Opportunity Purpose

Through this Notice of Funding Opportunity (NOFO), the National Cancer Institute (NCI) solicits applications for research on novel therapies for adult glioblastoma (GBM). The goal is to improve the treatment of adult GBM by developing novel effective agents that can cross the blood brain barrier (BBB) and testing them clinically. Successful early-stage trials of new drugs from this NOFO would transition seamlessly to later stage trials using well-established NCI clinical trial mechanisms.

To implement this concept, a highly collaborative GBM Therapeutics Network (GTN) of cross-cutting teams will be established, each team capable of driving therapeutic agent(s) from pre-clinical development, through investigational new drugs (IND) studies, into pilot clinical studies in humans. Appropriate therapeutic agents include: (1) novel agents or (2) agents or combinations approved for other indications and repurposed for treatment of GBM following appropriate preclinical studies. The scope of the NOFO, from late pre-clinical through early (Phase 0/1) clinical studies, uniquely spans a gap in the GBM drug development process.

Funding Opportunity Goal(s)

To improve screening and early detection strategies and to develop accurate diagnostic techniques and methods for predicting the course of disease in cancer patients. Screening and Early Detection research includes development of strategies to decrease cancer mortality by finding tumors early when they are more amenable to treatment. Diagnosis research focuses on methods to determine the presence of a specific type of cancer; to predict its course and response to therapy, both a particular therapy or a class of agents; and to monitor the effect of the therapy and the appearance of disease recurrence. These methods include diagnostic imaging and direct analyses of specimens from tumor or other tissues.

To develop the means to cure as many cancer patients as possible and to control the disease in those patients who are not cured. Cancer Treatment Research includes the development and evaluation of improved methods of cancer treatment through the support and performance of both fundamental and applied laboratory and clinical research. Research is supported in the discovery, development, and clinical testing of all modes of therapy including: surgery, radiotherapy, chemotherapy, and biological therapy including molecularly targeted therapies, both individually and in combination. In addition, research is carried out in areas of nutritional support, stem cell and bone marrow transplantation, image guided therapies and studies to reduce toxicity of cytotoxic therapies, and other methods of supportive care that may supplement and enhance primary treatment.

Key Dates

Posted Date

August 31, 2026

Open Date (Earliest Submission Date)

September 01, 2026

October 01, 2026

October 01, 2026

Not Applicable

July 2027

January 11, 2027

January 11, 2027

Not Applicable

December 2027

All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

Expiration Date

January 11, 2027

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Multi-Project (M) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

Part 1. Overview Information Key Dates Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose The overall goal of this Notice of Funding Opportunity (NOFO) is to improve the treatment of adult Glioblastoma Multiforme (GBM) by developing novel effective agents that can cross the blood brain barrier (BBB) and testing them in the clinic. To implement this initiative, multi-institutional teams are invited to participate in the Glioblastoma Therapeutics Network (GTN). Each GTN team is expected to drive therapeutic agent(s) from late pre-clinical development, through IND studies, into pilot clinical studies in humans. Successful early-stage trials of these new drugs would transition seamlessly to later stage trials using well-established NCI clinical trial mechanisms.

Definitions and Acronyms for this NOFO

Background Limited progress has been made in the treatment of adult GBM despite enormous public and private investments in basic, translational, and clinical research. The standard of care (maximal surgical resection followed by adjuvant radiation and temozolomide chemotherapy) has not changed in 15 years and yields a median survival of about 15 months and a 5-year survival of < 5%. Distinct pathophysiologic challenges at least partially explain the lack of progress in GBM therapies. First, GBM is a locally infiltrative brain malignancy without a well-defined border; surgical resection cannot be extended to obtain a tumor free margin. Therefore, adjuvant chemotherapy and radiation therapy (RT) are required after surgery, and the clinical efficacy of these two modalities is critical to treatment success. Second, agents for brain tumors must cross the blood-brain-barrier (BBB) to have a therapeutic effect; poor BBB penetration can lead to limited anticancer activity despite systemic toxicities. Third, in the setting of RT, the dose is limited by RT tolerance of normal brain parenchyma. Finally, the efficacy of other therapies, including targeted agents and immunotherapy, is impeded by GBM's intratumoral genetic heterogeneity and its immunosuppressive tumor microenvironment, which is marked by scant effector T-cell infiltration, preventing the antitumor efficacy of immune checkpoint inhibitors. Clearly, the development and selection of specific agents for GBM need to break new ground if effective treatments are to be found for this disease.

This long-standing unmet need is being addressed by the GTN, which has advanced several agents into early phase clinical trials, with the potential for introduction of additional novel agents in the future. The GTN is a unique framework for team science and improved rigor in preclinical drug development within the GBM community, providing a hub to accelerate movement to the clinic. Key elements of the ongoing GTN, including network coordination, cross-GTN collaborative pilot projects, and administrative oversight by Steering and Executive Committees, will remain in the proposed GTN. The future GTN will incorporate increased emphasis on engaging the external GBM community and timely movement of agent(s) to the clinic.

Specific Research Objectives of this NOFO The purpose of this NOFO is to build upon momentum established in the GTN's initial phase by establishing a network (GTN) of highly collaborative U19 teams, each team capable of driving therapeutic agent(s) from pre-clinical development, through IND studies, into pilot clinical studies in humans. Agents proposed for development in the GTN should not have been tested previously in GBM patients. Appropriate development candidates include: (1) novel agents or (2) agents or combinations approved for other indications and repurposed for treatment of GBM following relevant preclinical studies. As developing drugs from the discovery phase is a long, expensive process that often encounters obstacles and failures, this NOFO focuses on agents in the Preclinical Development stage. A unique aspect of the GTN will be the ability of members to leverage models and methodologies for cross-validation of promising agents across the network.

NCI's current research infrastructure (notwithstanding its extensive clinical trials capabilities) needs to expand critical drug development capabilities that are required for a comprehensive, full-scale effort to develop and test effective GBM therapeutic strategies. This would include the qualification of new BBB-penetrating drugs and combinations of therapeutic modalities (including other small molecule and biological agents, and radiation therapy), and the development of functional biomarkers to demonstrate that drugs and/or combinations reach their tumor or microenvironment targets. Successful evaluation of these novel agents and combinations in clinically relevant preclinical models and early-phase proof-of-mechanism clinical trials (that include pharmacokinetics [PK], molecular pharmacodynamic [PD] assays, and imaging) could lead to the translation of new agents into later-stage GBM clinical trials.

Research Scope and Structure of this NOFO Overall:

Refer to the NCI NCAB videocast (September 4, 2025) for further details on the GTN. Information specific to biopharmaceutical development may be found here.

Network Coordinating functions in Administrative Cores:

Upon funding, the GTN Coordinating Working Group will meet to determine necessary functions and how they will jointly perform them.

Research Projects and Shared Resources Cores:

Steering Committee (SC): A Steering Committee (SC) will be formed during the first year of the GTN. Refer to Section VI.2 Cooperative Agreement Terms and Conditions for details.

Executive Committee (EC): An Executive Committee will be formed during the first year of the GTN. Refer to Section VI.2 Cooperative Agreement Terms and Conditions for details.

Responsiveness to this RFA The following non-exhaustive list of examples, in support of a focused drug development effort with a near term trajectory to pilot clinical testing would be responsive to this RFA. Studies that:

Non-responsive Applications Applications considered to be non-responsive to this NOFO and not eligible for review include applications that:

IMPORTANT NOTE: Applicants uncertain whether their intended project meets the requirements of this NOFO are encouraged to send an email as listed in Section VII.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument

Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed

New

Renewal

The OER Glossary and the How to Apply - Application Guide provides details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Required: Only accepting applications that propose clinical trial(s).

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

NCI intends to commit $4.4 million (total costs) in FY 2027 to fund 3-4 awards. Future year amounts will depend on annual appropriations.

Award Budget

Application budgets are limited to direct costs of $700,000 per year. Costs need to reflect the actual needs of the proposed project.

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 5 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Local Governments

Federal Governments

Eligible Agencies of the Federal Government

U.S. Territory or Possession

Other

Independent School Districts

Public Housing Authorities/Indian Housing Authorities

Native American Tribal Organizations (other than Federally recognized tribal governments)

Faith-based or Community-based Organizations

Regional Organizations

Foreign Organizations/International Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organization) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Required Registrations

Applicant organizations Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code. Foreign organizations must obtain a NATO Commercial and Government Entity (NCAGE) Code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.

Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. Obtaining an eRA Commons account can take up to 2 weeks.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply - Application Guide.

Investigators can serve as a PI/multi-PI on only one GTN U19 application. However, investigators may have other roles (i.e., project leader, Core director) on multiple GTN U19s concurrently, even from more than one institution. Each lead institution is limited to one GTN U19 application.

2. Cost Sharing This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2- Definitions of Terms.

3. Additional Information on Eligibility Number of Applications

Only one application per institution (normally identified by having a unique entity identifier (UEI) number or NIH IPF number) is allowed The NIH will not accept duplicate or highly overlapping applications under review at the same time per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

Section IV. Application and Submission Information

1. Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this NOFO. See the administrative office for instructions if planning to use an institutional system-to-system solution.

2. Content and Form of Application Submission It is critical that applicants follow the Multi-Project (M) Instructions in the How to Apply - Application Guide, except where instructed in this notice of funding opportunity to do otherwise (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts) and where instructions in the How to Apply - Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

Required

Required

Required

Required

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in How to Apply- Application Guide and should be used for preparing a multi-component application.

Overall Component When preparing the application, use Component Type 'Overall'.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions, as noted.

SF424(R&R) Cover (Overall) Complete entire form.

PHS 398 Cover Page Supplement (Overall) Follow standard instructions.

Research & Related Other Project Information (Overall) Follow standard instructions.

In addition to standard items, describe existing facilities and/or other resources (such as existing institutional shared resource cores) available to the proposed U19.

As applicable and pertinent to the proposed research, describe partnerships (e.g., with industrial entities) that will provide relevant capabilities.

Project/Performance Site Locations (Overall) Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Research and Related Senior/Key Person Profile (Overall) Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this NOFO) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

Budget (Overall) The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A minimum total effort for each Overall PD/PI or MPI of the U19 is 2.4 person months (PM) in aggregate for all functions served on the U19; effort cannot be reduced below this level during the entire project period.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

PHS 398 Research Plan (Overall)

Overall Specific Aims: List the aims of the proposed U19. Summarize the expected outcome(s) of the U19 as a whole, including the impact that the results of the proposed translational research will have on GBM treatment. Briefly, describe how the U19 is structured and how the components alone and together fit into the overall goals.

Overall Research Strategy: This section should summarize the structure and the overall research strategy for the multi-component, multi-institutional application. The overall concept of the U19 should be conveyed by describing how the development and testing of novel therapies for GBM will be approached. Summarize the special features in the environment and/or resources that make this U19 strong or unique to the overarching goals of the GTN. The Research Strategy should be organized into sections that address the following: Overall Significance; Overall Innovation; Overall Approach; Overall Investigators; and Overall Environment. Specifics of Research Projects and Cores should be described separately.

Overall Significance

Overall Innovation

Overall Approach

Overall Investigators

Overall Environment

Renewal applications:

Letters of Support: Attach letters of support relevant to the Program as a whole (e.g., letters of institutional support). Letters of support relevant to specific Projects or Cores should be attached in the relevant Project or Core Research Plan forms.

Resource Sharing Plan:

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s):

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed. The Data Management and Sharing (DMS) Plan must be provided in the Overall component.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in How to Apply- Application Guide; any instructions provided here are in addition to the How to Apply - Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall) When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - Application Guide, with the following additional instructions:

If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information All instructions in the How to Apply - Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply- Application Guide must be followed.

PHS Assignment Request Form (Overall) All instructions in the How to Apply- Application Guide must be followed.

Administrative Core When preparing your application, use Component Type 'Admin Core.' All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Administrative Core) Complete only the following fields:

PHS 398 Cover Page Supplement (Administrative Core) Follow standard instructions.

Research & Related Other Project Information (Administrative Core) Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions.

Vertebrate Animals: Answer only the 'Are Vertebrate Animals Used?' question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Administrative Core) List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Administrative Core) ASSIST will default to "Project Lead". If you would like to use a different category, then replace "Project Lead" below with a different Category (e.g., Core Lead).

Budget (Administrative Core) Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

At least one of the U19 overall PD/PI(s) is expected to serve as Core Lead of the Administrative Core with a minimum effort of 0.6 person months. If multiple PD/PIs serve as co-leads of the Administrative Core, each is expected to devote at least 0.6 person months. The minimum total effort for each PD/PI or MPI of the U19 is 2.4 person months in aggregate for all functions served on the U19. A Network Coordinating Subgroup (NCS) Administrator with a minimum of 0.6 person month effort must be designated as key personnel.

Restricted Funds for cross-GTN Projects

Travel Travel funds must be included in the proposed budget to support travel for at least one U19 PD/PI to participate in face-to-face Steering Committee Meetings, if appropriate.

Budgets and activities for the Network Coordinating Subgroup and the U19 Administrative Core should not overlap.

PHS 398 Research Plan (Administrative Core) Specific Aims: Succinctly describe the specific objectives and goals of the Administrative Core.

Research Strategy: The following aspects should be addressed:

Leadership

Administrative management

Planning and evaluation

Integration of U19 components Explain how coordination and communication among the Research Projects, Shared Resources Core(s), and participating institutions will be achieved at the overall program level.

Interactions with other U19s

Interaction with the Network Coordinating Subgroup (NCS) Explain how leadership of the U19 Administrative Core will support responsibilities of the Network Coordinating Subgroup

Renewal applications:

Include a Progress Report that discusses the accomplishments of the Administrative Core during the current funding period, and the rationale for significant changes that may have occurred during the current funding period.

Network Coordinating Subgroup (NCS) The Administrative Core of each U19 Center must include an NCS with responsibilities and leadership distinct from those of the U19 Center's Administrative Core. The overarching function of the Network Coordinating Subgroup (NCS) is to work with NCSs from other U19 Centers for harmonization of administrative, scientific and clinical activities. Although the responsibilities of each NCs will be shared with other NCSs, each NCS must explain their capabilities to perform the functions listed below.