Part 1. Overview Information

Key Dates

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).

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

Through this Notice of Funding Opportunity (NOFO), the National Cancer Institute (NCI) intends to establish Next Generation Chemistry (NGC) Centers to identify and develop small molecules that disrupt the activity of fusion oncoprotein drivers for high-risk solid tumors and brain cancers. The NGC Centers will collaborate with other research groups within the Targeting Fusion Oncoproteins in Childhood Cancers (TFCC) Network, to be funded by the National Cancer Institute (NCI). The objective of the NGC Centers is to accelerate the discovery and development of novel small molecule therapeutics for the treatment of fusion-derived childhood cancers. Through the companion NOFO, RFA-CA-23-036, the NCI solicits U01 applications for the TFCC Network, which will be independent research projects intended to advance our understanding of the mechanisms of action of fusion oncoproteins in pediatric cancers with the goal of identifying novel drug targets and critical dependencies. Small molecules are defined here as chemically synthesized drug-like compounds with molecular weights <2000 Da that can cross cell membranes to modulate fusion-oncoprotein functions.

Each NGC Center will consist of a multidisciplinary group of scientists with appropriate expertise to further the development and evaluation of novel compounds that directly inhibit fusion oncoprotein activity, block critical interactions, or selectively degrade fusion oncoproteins or their critical dependencies. It is anticipated that the dynamic interactions of multidisciplinary groups of investigators comprising the UM1 and U01 recipients, and the program staff at the NCI, will pursue a concerted effort necessary to: 1) foster new collaborations between medicinal chemists, molecular biologists and pediatric oncologists; 2) increase the availability of chemical probes, tools, or advanced leads for further optimization to new drug candidates suitable for testing in humans; 3) facilitate the development and validation of new technologies and strategies for targeting fusion oncoproteins or their critical dependencies through inhibition, stabilization or degradation approaches; and 4) help exploit functional domains, critical dependencies and vulnerabilities for effective treatment of childhood cancers.

The intent of the NGC Center program is to accelerate the development of effective compounds suitable for treatment of fusion oncoprotein-driven pediatric cancers, especially in areas of unmet medical need.

Background

Recurrent translocations producing fusion oncoproteins are a hallmark of many childhood cancers and are pathognomonic of specific cancer types. These translocations generate fusions of normal proteins that become oncogenic, often by dysregulating protein complexes that control gene expression or chromatin state, thus altering developmental programs that lead to transformation of the unique cell of origin for each cancer. Fusion oncoproteins are well-defined cancer drivers that are often found in cancers with few other genetic lesions. Therefore, fusion oncoproteins represent highly credentialed targets for potential therapeutic development. While the absolute specificity of fusion oncoproteins for tumor cells suggests that these proteins can be exceptional therapeutic targets, the search for effective inhibitors has been hampered by the largely undruggable nature of transcriptional regulators, the lack of understanding of fusion oncoprotein function, and gaps in our knowledge of the interactome and critical dependencies of fusion oncoproteins. In 2017, the Pediatric Cancer Working Group of the NCI Cancer Moonshot Blue Ribbon Panel (BRP) identified childhood and adolescent cancer fusion oncoproteins as a priority research area. In response to this recommendation, the NCI established the Fusion Oncoproteins in Childhood Cancers (FusOnC2) Consortium, a group of Cancer Moonshot-funded Research Centers each taking a multidisciplinary, comprehensive approach to advancing understanding of the mechanisms of action of fusion oncoproteins in pediatric cancers, with a goal of applying this knowledge towards developing targeted therapeutic approaches. FusOnC2 Consortium members have made tremendous research advances, and NCI hopes to capitalize on the success of the Moonshot program to continue research in this area to develop effective new treatments for patients affected by these cancers.

Progress in our understanding of fusion-driven cancer biology, along with recent technological developments, now provide an opportunity to coalesce a community towards generating fusion-oncoprotein targeted small molecule agents. Remarkable advances in chemical biology have dramatically expanded the universe of druggable protein targets. Success in targeting transcriptional regulators, enhanced chemoproteomic approaches, and other enabling technologies now provide plausible new strategies for direct targeting of fusion oncoproteins and the proteins with which they interact as part of biologically active complexes. Significant advances in medicinal chemistry degrader-based technologies such as heterobifunctional proteolysis targeting chimeras (PROTACs) and molecular glues now provide a rich knowledge base for developing rational therapies for fusion-driven childhood cancers. While directly targeting fusion oncoproteins would be ideal because of their exclusivity in these tumors, other targets (e.g., interacting proteins, synthetic lethal partners, downstream modulators of fusion oncoprotein function) may be more amenable to these strategies. Thus, the design of this Network combines therapeutic approaches with continued mechanistic studies to reveal novel potential drug targets and accelerate development of effective compounds and agents for treatment of fusion-driven cancers.

Research Objectives, Focus, and Requirements

The goal is to establish NGC Centers for Fusion Oncoproteins. Each NGC Center application should contain collaborative research projects by a multidisciplinary group of investigators focused on the discovery and development of small molecules to target fusion oncoprotein-driven pediatric cancers. Successful applicants will work within the context of a collaborative research network, the TFCC Network, to accelerate innovative drug discovery and preclinical development of therapeutics for fusion oncoprotein-driven childhood cancers. Each NGC Center will address discrete, relevant research opportunities pertaining to the development of novel pharmacologic agents for the treatment of one or more fusion oncoprotein-driven pediatric cancers. The NGC Center is expected to have capabilities that encompass relevant aspects of preclinical drug development and biological testing.

Applications focusing on fusion oncoproteins found in tumors that have high risk of treatment failure and for which there has been little progress in identifying targeted agents are strongly encouraged. As such, fusion oncoprotein targets for which clinical proof of concept has been achieved will be excluded from eligibility. Applications focused on pediatric solid tumors and brain cancers are particularly encouraged.

Potential areas of investigation depending upon project scope include, but are not limited to:

• Discovery and preclinical testing of novel compounds for fusion oncoprotein-driven pediatric cancers;
• Identifying and developing small molecules to effectively modulate the activities of individual fusion oncoproteins, block critical fusion protein interactions, interact with coding and/or noncoding RNAs required for fusion protein oncogenesis, or selectively lead to fusion protein degradation;
• Utilization of novel approaches such as chemoproteomics to discover and validate novel drug candidates, including targeted protein degraders;
• Computer-aided drug discovery to allow structure-based drug design;
• Development and validation of novel, fusion oncoprotein-based functional assays for evaluating therapeutic compounds. Measures with potential translational utility are particularly encouraged; and
• Initial Good Laboratory Practice (GLP) toxicology, safety pharmacology, and pharmacokinetics to support an investigational new drug (IND) application.

To properly address the NOFO goals, each proposed NGC Center will be expected to include diverse areas of expertise to facilitate progression from structure-function biochemical data to small molecule drug candidates and setting the stage for preclinical in vivo testing. Relevant areas of expertise that could be included are (among others) chemoproteomics, structural biology, molecular biology, medicinal chemistry, and experimental therapeutics. Multi-institutional collaborations are strongly encouraged to achieve the breadth of expertise required for a comprehensive approach to developing effective therapeutic agents for fusion oncoprotein-derived pediatric cancers. An NGC Center can focus on one or more potential target(s), as appropriate for the proposed scope and budget.

To facilitate collaboration within the TFCC Network as well as with external researchers, each NGC Center will set aside 10% of its budget in years 2-5 for collaborative projects with either companion U01 grantees or with other research teams. Each NGC Center will be responsible for identifying collaborative projects in years 2-5 and for providing NCI with scientific justification for the merit of these projects.

Description of the NGC Center Activities and Organizational Framework

The overarching goal of the NGC Center program is to accelerate the development of novel small molecule therapeutic agents to treat fusion oncoprotein-derived childhood cancers. Each proposed Center is to consist of a multidisciplinary group of investigators with complementary skills that is committed to working together to achieve this goal. The overall structure of the Center is intended to facilitate coordinated and efficient drug discovery and development to produce potential therapeutic agents for recalcitrant fusion oncoprotein-driven pediatric cancers. The Center must include i) a Center Leadership Group (CLG), ii) up to four Research Groups, and iii) an Administrative Group (AG). These functional areas will be integrally connected to all aspects of the research agenda for developing potential therapeutics for fusion oncoprotein-driven childhood cancers.

Center Leadership Group (CLG) , led by the PD(s)/PI(s) of the Center, is responsible for review and discussion of scientific direction, oversight, coordination, and evaluation of NGC Center activities. The CLG will include the Leaders of all Groups within an NGC Center . It will function as a collaborative platform for discussion and prioritization of research concepts, deriving input from key project personnel, consulting expert advisors, and the scientific literature. The CLG will develop, coordinate, monitor and periodically provide updates on Center priorities and initiatives to ensure progress.

NGC Research Groups: Two to four research groups should be specified as components of the NGC Center. These should be selected and organized by the applicant to optimize the likelihood of the Center’s success in identifying small molecules with therapeutic potential against specific fusion oncoproteins. Potential areas of focus for the research groups include, but are not limited to, medicinal chemistry, computational and structural biology, biological testing (e.g., in vitro and in vivo studies, and ADME/DMPK), statistics/data management, etc.

The Administrative Group (AG) provides administrative support for the Center, organizes meetings, compiles summaries, facilitates communications, and prepares reports. The AG will coordinate research and data sharing documents for the CLG.

Non-Responsive Applications

The following types of studies are beyond the scope of this NOFO. Applications proposing such studies will be considered non-responsive and will not be reviewed.

• Applications focusing on studies of the biology of fusion oncoproteins
• Applications focusing on molecular mechanisms by which fusion oncoproteins drive pediatric cancers without any preclinical therapeutic endpoints.
• Development of in vivo or in vitro models of pediatric tumors when the purpose is to interrogate basic oncogenic pathways or mechanisms.
• Applications focusing on developing therapies for targets that already have a clinical proof of concept.
• Applications focusing on developing therapies for targets which are not fusion oncoproteins.
• Applications focusing on the development of agents which are not considered small molecules.

Applicants are advised to contact the Scientific/Research Contact with any questions they may have regarding the responsiveness of their application.

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

Section II. Award Information

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

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Government

• 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

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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 allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) 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. The NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• 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.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an 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.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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 their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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 SF424 (R&R) Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

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:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Joseph K. Agyin, Ph.D., M.B.A.
National Cancer Institute (NCI)
Telephone: 240-276-7873
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The Research Strategy must consist of the following subsections with the indicated page limits:

• Subsection A: NGC Center: Organization, Leadership and Overall Research Plan; 12 pages.
• Subsection B: Research Groups; minimum of two Groups, maximum of four Group; 24 pages.
• Subsection C: Administrative Group: 6 pages.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this NOFO.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

Facilities & Other Resources

• Data Management Facilities: Describe the unique facilities and features of the data management section to support the processes for the reliable and accurate collection and recording of the data, and the features of the facilities that will enable rapid and secure transfer of data types within the Center and from collaborating organizations. Describe data management, key outcome measures, statistical approaches, overall data management, and plans for information transfer to and interactions with the Statistical and Data Management Group.
• Laboratory Resources and Facilities: Describe the unique aspects of the facilities supporting the Research Groups and the existing infrastructure for carrying out small molecule drug development and estimating therapeutic efficacy, safety, and pharmacology.
• Equipment: Describe any special equipment available for handling hazardous chemicals, biohazards, or other potentially dangerous substances.

All instructions in the SF424 (R&R) Application Guide must be followed.

In line with the interdisciplinary collaborative nature of this initiative, it may be appropriate to have at least one PD/PI with medicinal chemistry and at least one with biologically active small molecules evaluation and drug development expertise.

R&R Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

Applicants must budget for the following:

• In the budget justification, provide a detailed apportionment of the PD(s)/PI(s) time to oversee management and research activities associated with the NGC Center functions.
• Include separate budget justifications for each Research Group.
• In line with the interdisciplinary collaborative nature of this initiative, it may be appropriate to have up to four PDs/PIs. This could potentially include at least one PD/PI with medicinal chemistry and at least one with biologically active small molecules evaluation and drug development expertise.
• 10% of budget in years 2-5 is required to be set aside for collaborative projects with the companion U01 grantees or other collaborations approved by the NCI.
• The PD/PI must commit a minimum of 1.8 person-months effort per year to the UM1 award. The commitment cannot be reduced in later years of the award. If there are multiple PD(s)/PI(s), each must devote a minimum of 1.2 person-months effort per year.
• One day initial Kick-Off Meeting within the first 6 months of the award to be held either online or in-person for the PD(s)/PI(s) and key personnel.
• Annual Programmatic meetings, to be held annually beginning in Year 2, likely in the Rockville, MD area (2 days per annual meeting) for the NGC Centers PD(s)/PI(s) and key personnel to update NCI on progress and future directions.
• Total budget for the CLG and AG should be limited to 6% ($150,000) of the total cost of the NGC Center budget.

The budget justification should include a breakdown of the apportionment of funds for each of the proposed Groups for the first year. The budgets for out-years should represent best estimates for the general research plan. Resource allocations are expected to change over time from what is initially proposed.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy: Organize the research strategy section with subsections in the specified order and using the instructions provided below. Start each subsection with the appropriate subsection heading:

Subsection A. NGC Center: Organization, Leadership and Overall Research Plan (page limit: 12 pages)

• Organization
  • Describe the overall scientific problem the NGC Center is designed to address, including the fusion oncoprotein target(s), the rationale for selecting this target, and the central theme and goals of the NGC Center
  • Describe how the overall structure and organization of the NGC Center is uniquely designed to address this scientific problem.
• Leadership
  • Briefly describe the organization of the CLG and discuss how the structure promotes effective leadership in establishing the CLG research agenda and the Research Groups. Include the following:
    • Describe decision-making in the proposed organization toward the ability to prioritize and recommend potential research directions based on results from the Research Groups (e.g., decision-making for prioritizing leads for preclinical testing in pediatric cancer models).
    • Discuss processes, procedures, and plans, including frequency, of the CLG to convene scientific and programmatic meetings to communicate scientific progress, and to identify new research opportunities and potential avenues of collaboration, both within the TFCC Network and with other stakeholders. Without duplicating information in the biosketches, discuss the suitability of the PD(s)/PI(s) to develop, manage, and direct an integrated and focused NGC Center, and manage collaborations.
    • Discuss the procedures and processes by which the CLG will direct and oversee dissemination of results to the research community.
• Overall Research Plan
  • Provide the overarching research plan for the proposed NGC Center that encompasses contributions from each individual Research Group to meet NGC Center goals and objectives.
  • Explain the proposed contribution of each of the individual Research Groups towards achieving the objectives of the Center, including a clear description of how each Research Group is required for the attainment of NGC Center’s objectives, including available professional and technical personnel to permit efficient and successful conduct of the proposed research.
  • Describe the innovative elements of the research plan and the potential to advance scientific knowledge and contribute to the quest for effective treatment modalities for fusion oncoprotein-driven pediatric cancers.
  • Describe the feasibility of the proposed research plan of the NGC Center to develop potential drug candidates for fusion oncoprotein target(s) within the proposed budget and project duration.
  • Summarize the special features in the collaborative arrangements that make this application strong or unique.
  • Describe the system procedures and workflows for the collection, storage, access, backup, and archiving data for the NGC Center, and the exchange of data across the Research Groups of the NGC Center.
  • Provide a tentative sequence or timetable for the overall research program.

Subsection B: Research Groups (minimum of 2 Groups, maximum of 4 Groups; page limit: 24 pages)

• Describe the aims and functions of each Research Group (6-page limit for each Research Group) in a separate section that addresses their research approaches and contributions to the NGC Center.
• Describe the specific aims, any preliminary data (if available), novel strategies, technologies, and techniques of each Research Group and how they will be used to design, synthesize, and characterize promising drug candidates to target fusion oncoprotein-driven childhood cancers, as well as strategies to optimize potential leads.
• Describe the scientific integration of each Research Group within the NGC Center and the proposed organizing framework and a rationale for how each project will help, within the funded period, generate sufficient results to drive the development of novel therapeutic strategies for fusion-derived childhood cancers based on the proposed organizing framework.
• For Research Groups that include medicinal chemistry activities, provide clear descriptions of any special capabilities of the Program, such as nuclear magnetic resonance (NMR), x-ray crystallography, chemical biology, computer-aided drug design, chemoproteomics for small molecule drug discovery and expertise in targeted protein degradation techniques using proteolysis targeting chimera (PROTAC), molecular glue degraders, or other innovative approaches. Summarize each Group’s track record of previous accomplishments in developing promising drug candidates targeting undruggable fusion oncoproteins.
• For Research Groups that include the biological evaluation of preclinical small molecule drug candidates, describe (as relevant) the model systems available for in vitro and in vivo testing, the strategy for PK-PD modeling or other mathematical and computational approaches to integrate data across different model systems or platforms to better predict therapeutic outcomes of drug candidates for childhood cancers, ADMET or other approaches to help predict and identify drug candidates, and new/innovative assays that will be assessed and implemented for use, including how decisions will be made on their use.
• Outline the system procedures and workflows for the collection, storage, access, backup, and archiving of data, and for the exchange of data with other Research Groups of the NGC Centers. Include plans for system security and for long-term maintenance of data and data systems.
• Discuss the potential difficulties and limitations of the proposed procedures and alternative approaches to achieve the aims.

Subsection C: Administrative Group (AG) (page limit: 6 pages)

• Describe the AG Leader's experience in similar preclinical drug development research efforts.
• Describe the organizational structure, proposed staffing plans, and lines of authority for the AG.
• Discuss the processes and procedures to establish effective project management of AG activities.
• Describe the fiscal management plan for the Center to administer and track the Center budget and associated expenditures and reports.

Letters of Support:

The Letters of Support attachment should begin with a table of letter authors, their institutions, and the type of each letter (institutional commitment, supply of study materials, or resources; collaboration or role in the project; potential or current user of a resource or service proposed in the application).

Provide all appropriate letters of support, including any letter necessary to demonstrate the support of NGC Center participants, laboratories, and other collaborators. If parts of the research costs are to be borne by sources other than NIH, these contributions must be presented in detail as part of supporting letters signed by an Authorized Organization Representative. These outsource costs do not constitute cost sharing as defined in the current NIH Grants Policy Statement and should not be presented as part of the requested budget.

To document their commitment, include letters of support from the following:

Product development partnerships; laboratories; and sources for the availability of study reagents, candidate compounds and pharmaceutical products.

Resource Sharing Plan:

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

• Applications must address an Intellectual Property (IP) plan. Since this research will include several institutions, including the private sector, complex IP situations may arise. To avoid delays in implementing drug development goals, the Center is required to provide a plan as part of the application, detailing (1) the approach to be used for obtaining patent coverage and for licensing, where appropriate; (2) a statement demonstrating acceptance of the approach, signed by all parties; (3) a description of procedures to be followed for the resolution of legal problems that potentially may develop; and (4) a list of existing patents/licenses related to the proposed research.

The agreement among the institutions comprising the Center, signed, and dated by the organizational officials authorized to enter into such arrangements for each Group member and member institution, must be submitted with the application. If the Group wishes to place all inventions and discoveries resulting from these studies within the public domain, a letter to that effect must be submitted in lieu of the agreement. The letter must be co-signed by the PD/PI(s), each of the Group Leaders, and each of the business officials representing the respective institutions.

• It is NIH policy that the results and accomplishments of the activities that it funds should be made available to the public. PD/PIs and recipient organizations are expected to make the results and accomplishments of their activities available to the research community and the public at large. Investigators conducting biomedical research frequently develop unique research resources. NIH considers the sharing of such unique research resources (also called research tools) an important means to enhance the value of NIH-sponsored research. Restricting the availability of unique resources can impede the advancement of further research. At the same time, NIH recognizes the rights of recipients to elect and retain title to subject inventions developed with federal funding pursuant to the Bayh-Dole Act. See the Office of Extramural Research, Division of Extramural Inventions & Technology Resources (DEITR), Intellectual Property Policy page: http://grants.nih.gov/grants/intell-property.htm.

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
• If applicable, all investigators funded under this NOFO will be expected to share their data publicly through NCI supported Bioinformatics Center(s). Therefore, if needed, the Data Management and Sharing (DMS) plan should include a summary of how the applicant will manage data submission and interactions.

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) 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, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NCI, NIH. Applications that are incomplete, non-compliant, and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this NOFO: To what extent will this program, as proposed, advance the development of small molecule therapeutics targeting fusion oncoprotein-driven childhood cancers? What is the likelihood that the results of the proposed studies will contribute to the development of small molecule drugs for fusion-driven pediatric cancers?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the project?

Specific to this NOFO: How sufficient are the proposed commitment and level of effort of the PD/PI to ensure the success of the projects? How well does the proposed Research Group members experience relevant to developing and evaluating small molecule drug candidates?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this NOFO: To what extent are the proposed approaches novel in their application to therapeutics development for fusion oncoprotein-derived pediatric cancers?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this NOFO: How well are the structure of the NGC Center and its scientific leadership plan as implemented through the CLG aligned to provide the direction needed to integrate and direct the activities of the Research Groups to successfully meet the Center’s objectives? To what extent do the proposed Research Groups provide complementary expertise that contributes to the likelihood of success in meeting the small molecule identification objective? How well do the Research Groups plans for data management and the Center’s plans for access to data across the different Research Groups meet the Center’s needs in supporting collaborative development of small molecules? If models are proposed to test novel drug candidates, are these appropriate and clinically relevant?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment, and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable.

Renewals

Not Applicable.

Revisions

Not Applicable.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NCI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a condition of receiving the grant, to administer programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity, The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. See https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

• For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH's purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

The PD(s)/PI(s) will have the following primary responsibilities:

• Planning and conducting the operations defined by the terms and conditions of the cooperative agreement award. This includes determining research approaches, designing protocols, setting project milestones in consultation with NCI staff, and ensuring scientific rigor.
• Design and implement the CLG to provide scientific direction, oversight, coordination, and evaluation of NGC Center activities.
• Conducting the scientific research in the project, reporting progress and milestones or objectives to NCI staff, reporting results to the scientific community, and disseminating approaches, methods, models, and tools broadly.
• Assuming responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of the research and administrative functions supported under this NOFO in accordance with the terms and conditions of award, as well as all pertinent laws, regulations and policies.
• Participating in a cooperative, interactive, and collaborative manner with NCI staff, other TFCC Network investigators, and one another to maximize impact of the TFCC Program and meet Program goals and objectives. This includes becoming a member of the TFCC Network Steering Committee (SC), that is responsible for the governance of TFCC activities (as described below).
• Maintaining the confidentiality of the information developed or handled by the TFCC Network, including, without limitation, unpublished data, protocols, data analysis, confidential exchanges between members of the TFCC Network, as well as any confidential information received by third party collaborators.
• Facilitating the public release and dissemination of results, data, reagents, models, technologies, and other products generated through this award broadly and in a timely manner. The PD/PI is expected to share resources generated through this award in accordance with the approved plan for making quality-assured materials available to the scientific community and the NIH as written in the final version of the grant application, and consistent with NIH resource sharing policies and goals of the NOFO, and recommendations developed and approved by the SC.
• Ensuring that any industry collaborations are governed by an appropriate research collaboration agreement with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH policies and procedures and any policies and procedures developed by the SC.
• Operating in accordance with processes and goals as delineated in the NOFO, and in accordance with the goals, priorities, procedures, protocols, and policies agreed upon by the TFCC SC, to the extent consistent with grants regulations. This includes compliance with program policies including, as applicable, policies on: the use of common protocols, publication of study results, collaborative procedures, confidentiality, and sharing plans to be developed by the SC in collaboration with NCI.
• Identifying collaborative projects in years 2-5 that involve either TFCC Network U01 research teams or external research teams and then providing NCI with scientific justification for the merit of these projects
• Attending an initial face-to-face Kickoff Meeting of the TFCC PDs/PIs, followed by at least one TFCC investigator meeting annually.
• Adhering to a Network Communication Plan: A consensus Communication Plan will be drafted by the TFCC SC during the kickoff meeting. This plan will clearly spell out interactive requirements that all TFCC investigators are expected to follow, including:
  • Participation in regular conference calls with fellow TFCC colleagues, including contribution to various subcommittees and working groups.
  • Participation and presentation of findings at the TFCC Annual Investigators' Meeting.
  • Coordination of efforts with other members of the TFCC Network.
  • Jointly publishing on TFCC collaborations in a timely manner.
• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

NCI program staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. The substantially involved NCI program staff member(s), acting as Project Scientist(s), will coordinate in a centralized fashion the various activities of the recipients . Specific responsibilities of the NCI Project Scientist(s) will include, but will not be limited to

• Advising the recipients on scientific topics as well as programmatic priorities.
• Assisting the network recipients as a liaison in stimulating their broader interactions with other NCI and NIH programs to disseminate results and outcomes and effectively leverage existing NIH/NCI resources and infrastructures (e.g., databases).
• Inform the network about pre-clinical resources available through NIH including drug development capabilities to which the groups may have access.
• Participating in the development and evaluation of trans-network activities.
• Assisting in avoiding unwarranted duplication of effort across the network.
• Monitoring the operations and progress of the UM1 recipients and making recommendations on overall project directions.
• Helping coordinate collaborative research efforts including approving restricted supplemental funding for collaborative activities.
• Attending TFCC SC meetings.
• The NCI Project Scientist and Program Officer will review the scientific progress of TFCC projects and will review all projects for compliance with sharing and operating policies developed by the TFCC SC and the NCI. Based on this review, the Project Scientist in conjunction with the Program Officer may recommend to the NCI to continue funding, or to withhold or restrict support for the grantee for lack of progress or failure to adhere to TFCC Network or NIH policies. Review of progress may include regular communications between the PD/PI and NCI staff, site visits, or fiscal review. The NCI also retains the option of organizing periodic external review of progress of the work supported by the TFCC award.
• The NIH reserves the right to terminate any TFCC award in the event of (1) A substantial shortfall in accomplishing the management goals and responsibilities as stated in the reviewed application, (2) A failure to meet the TFCC Network policies and procedures, (3) Substantive changes in the management of the TFCC award that are not in keeping with the objectives of the NOFO and/or (4) failure to make substantial progress towards milestones keeping in mind the agreed upon go/no-go decisions.

Additionally, an NCI Program Director acting as the Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

The TFCC Network Steering Committee (SC) serves as the main governing board of the Consortium. Close interaction among the participating investigators will be required, as well as significant involvement from the NCI, to develop Consortium guidelines and meet Program goals.

The SC will consist of the following members:

• PD(s)/PI(s) of each TFCC Project who will collectively have one vote for each U01 or UM1 grant funded through RFA-CA- 036 and RFA-CA-23-037 respectively, regardless of the number of PD/PIs designated;
• Designated NCI program staff, including potentially Program Directors and Project Scientists for each grant. NCI will collectively have one vote, regardless of the number of NCI staff members present;
• Other designated NIH program staff, patient advocates, TFCC Project staff, and external experts approved by NCI staff may attend the SC meetings on a regular or ad hoc basis but will not be voting members;
• Associate Members of the TFCC Network may be added by NIH staff as non-voting members through a process established by the SC.

The SC may decide to establish subcommittees for specific purposes. The NCI Project Scientists and Program Officers may serve on such subcommittees, as they deem appropriate.

All major scientific and administrative decisions will be determined by voting policies as established by the TFCC Network SC. NCI Project Scientists involved with the management of the TFCC Network will help the SC develop and draft sharing and operating policies that are in accordance with NIH guidelines.

The SC will formulate strategic decisions and guidelines for network-wide activities. The TFCC recipients will be required to accept and implement these decisions and guidelines to the extent consistent with applicable grant regulations. All SC scientific and administrative decisions and recommendations that require voting will be based on a majority vote. The TFCC SC will be constituted at the initial TFCC meeting and will meet regularly (monthly or quarterly), including at least once in-person during the annual TFCC Investigators' Meeting. The initial chairperson(s) of the TFCC SC will be selected by majority vote by the SC from the representatives of all recipients and is responsible for coordinating the TFCC activities, preparing meeting agendas, and chairing SC meetings in collaboration with NCI staff. At the end of 1 year of service, with NCI concurrence, the SC may ask the Chairperson(s) to serve a second 1-year term or choose a replacement for that role. NCI staff may also choose to replace the TFCC Network SC Chairperson(s) at any time based on poor job performance or failure to follow the relevant procedures and guidelines or other reasons. The replacement for the chairperson will also be selected by majority vote.

Primary responsibilities of the TFCC SC include, but are not limited to, the following activities:

• Establishing network policies and procedures.
• Establishing policies and procedures for collaborative projects, and protocols.
• Formulating policies and procedures for data collection and harmonization.
• Identifying impediments to success and strategies to overcome them.
• Developing shared tools for disseminating information about TFCC.
• Discussing important issues relevant to therapeutic development for pediatric cancers.
• Helping with the planning of major events (such as the annual meeting).
• Identifying opportunities for sharing techniques, materials, information, and tools.
• Facilitating communication and fostering collaboration across the TFCC.
• Reviewing the progress of the TFCC towards meeting the overall Network goals.
• Developing publication policies to facilitate collaborations and co-publications by TFCC members.
• Ensuring the TFCC leverages existing NIH resources and programs.
• Evaluating collaborative activities and providing feedback to the NCI Program Staff.
• Discussing the implementation of recommendations or suggestions from the NCI and any external consultants and plan a timely implementation strategy.

TFCC Network External Scientific Consultants (ESCs)

2-4 independent external experts may be appointed by NCI as External Scientific Consultants (ESCs). The ESCs would not form a committee but would be independent consultants who would meet in conjunction with a meeting of the TFCC Network, and/or meet by phone or web as needed to provide guidance and/or help the NCI with evaluation of the TFCC program. The ESCs would provide their perspectives to NCI on potential adjustments and future directions for the TFCC Network activities. This could include providing their assessments of the progress of the entire TFCC Network or individual recipients as well as commenting on potential changes in priorities for the Program based on scientific advances within and outside the Consortium. The ESCs would be senior, scientific experts who are not directly involved in the activities of the TFCC Network. NCI staff would have the opportunity to attend executive meetings with the ESCs. All members of the ESC would be given the opportunity to listen to SC meetings and to attend the annual TFCC Network Investigator meetings.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 and 2 CFR Part 200 Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Joseph K. Agyin, Ph.D., M.B.A.
National Cancer Institute (NCI)
Telephone: 240-276-7873
Email:[email protected]

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: [email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.