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

The overall goal of this Notice of Funding Opportunity (NOFO) and the companion NOFO, RFA-CA-23-037 , is to form a new dynamic network of investigators that will use rigorous and collaborative efforts to advance our understanding of the mechanisms of action of fusion oncoproteins in pediatric cancers and to apply novel chemical strategies to accelerate innovative drug discovery and preclinical development of therapeutics for fusion oncoprotein-driven childhood cancers. The primary goals of this network, the Targeting Fusion Oncoproteins in Childhood Cancers (TFCC) Network, are to build upon an enhanced understanding of the biology of childhood cancer fusion oncoproteins and upon advances in chemical biology and chemoproteomic approaches to identify additional therapeutic targets and develop novel treatment strategies. This NOFO solicits U01 applications for discrete research projects focused on molecular mechanisms by which fusion oncoproteins drive pediatric cancers with the goal of identifying potential drug targets and their critical dependencies. The companion NOFO, RFA-CA-23-037 , solicits UM1 applications for Next Generation Chemistry (NGC) Centers for Fusion Oncoproteins that will contain independent research projects utilizing innovative chemical biology technologies, medicinal chemistry, and chemoproteomic approaches to develop therapeutics that target fusion-driven cancers.

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 multi-disciplinary, comprehensive approach to advancing our 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 in order 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 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 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 through RFA-CA-23-037 with continued mechanistic studies through this NOFO 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

Research Scope and Objectives

Through this NOFO, NCI solicits applications for discrete research projects focused on molecular mechanisms by which fusion oncoproteins drive pediatric cancers. Successful applicants will work in the context of a collaborative research network, the Targeting Fusion Oncoproteins in Childhood Cancers (TFCC) Network, to advance our understanding of the mechanisms of action of fusion oncoproteins in pediatric cancers and to accelerate innovative drug discovery and preclinical development of therapeutics for fusion oncoprotein-driven childhood cancers. Each TFCC U01 recipient will address a discrete, relevant research opportunity pertaining to the mechanisms of action of fusion oncoproteins in pediatric cancers.

Applications must focus 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. As such, fusion oncoprotein targets for which clinical proof of concept has been achieved are excluded from eligibility. Applications focused on pediatric solid tumors and brain tumors are particularly encouraged.

Potential areas of investigation include but are not limited to:

• Defining the critical dependencies created by specific fusion oncoproteins through functional genomic screening in order to reveal potential drug targets;
• Defining how fusion oncoproteins influence gene expression, altering normal cellular programs to block lineage differentiation and development; and
• Identifying and characterizing protein complexes, non-coding RNAs, and/or post-translational modifications associated with fusion oncoproteins.

Collaborative Requirements

Once funded, the U01 recipients will be expected to work collaboratively with all members of the TFCC to share data and resources, discuss shared challenges, and work together to move the field forward.

Structure and Governance of the TFCC Network

The TFCC Network will include multiple U01 and UM1 recipients and will be governed by a Steering Committee (SC). The SC will be composed of representatives from the funded U01 and UM1 teams and the NCI. All U01 and UM1 recipients must be willing to serve on the Steering Committee. The SC will provide input towards and oversight of TFCC collaborative activities, as well as overall integration of efforts among all TFCC recipients. The initial Chair and any co-Chair of the SC will be PDs/PIs of TFCC cooperative agreement awards and will be selected by NCI staff. After the first year, subsequent Chairs or co-Chairs will be elected by the SC. Any member of the SC can offer nominations for the Chair and co-Chair, including self-nomination. Though the SC will make recommendations for Network activities and guidelines, all decisions must comply with NIH, DHHS, and Federal Guidelines, and NCI retains the right of final approval.

Additional details on the composition and functions of TFCC Steering Committee are provided in Section VI.2, Cooperative Agreement Terms and Conditions of Award.

Non-responsive Applications

The following types of activities remain outside the scope of this NOFO, and applications proposing them are non-responsive to this NOFO and will not be reviewed.

• Applications focusing on the large-scale detection and identification of new fusion proteins.
• Applications focusing of fusion oncoprotein targets for which clinical proof of concept has already been achieved.
• Applications primarily focusing on developing therapeutics for treatment of cancers caused by fusion oncoproteins.

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:

Keren Witkin, Ph.D.
National Cancer Institute
Telephone: 240-276-5371
Email: [email protected]

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

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.

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

R&R or Modular Budget

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

The PD/PI must commit a minimum of 1.8 person-months effort per year to the U01 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.

Budget requests must include costs for the PD(s)/PI(s) to attend the initial in-person TFCC kick-off meeting, and for the PD(s)/PI(s) and other members of the project team (up to four people in total) to attend the annual TFCC Investigators' meetings. PDs/PIs are encouraged to include early career scientists in Network activities and should include budget to travel at least one graduate student or postdoctoral fellow to the Annual Investigators Meeting.

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:

Specific Aims: Include the specific aims of the Research Project and provide a rationale and description of how it fits into organizing framework of the TFCC.

Research Strategy: Describe the research strategy using the standard sub-sections of Research Strategy (Significance, Innovation, and Approach) defined in the SF424 Application Guide with additional guidance as defined below. Identify clearly any innovative biological concepts that are proposed to be explored as a potential basis for mechanistic studies of fusion oncoprotein-driven childhood cancers. In addition to standard items, address all the aspects listed below in the sub-sections as indicated.

Under "Significance," address the following:

Explain the importance of the proposed research project in understanding fusion oncoprotein-driven pediatric cancers, and how the proposed approach could move the field forward towards identifying critical dependencies or potential drug targets.

Under "Innovation", address the following:

Highlight any innovative and/or unique concepts, experimental approaches, methodologies, novel cancer models, etc., that you have available and plan to use. Describe how these innovative features will enable unique understanding of the mechanistic basis of fusion oncoprotein-driven oncogenesis.

Under "Approach", address the following:

Project Timeline: A timeline of the initiation and completion of the specific aims/sub-aims is required. The timeline must be provided in a separate heading at the end of the Approach section.

In applications that include multiple institutions (particularly in separate geographical areas), descriptions of the logistics involved in carrying out the proposed aims to completion within the project period (how tasks that require various and sequential expertise, and how information sharing will be coordinated) must be included.

Health Disparities: If applicable to the type of research projects being proposed, the Research Strategy must address how minority health, health disparity populations or data will be integrated into the proposed studies.

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.

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.

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 for this NOFO: How well are the vision and scientific focus of the proposed project designed to enable a unique understanding of the mechanistic basis of fusion oncoprotein-driven oncogenesis? How well will the project lead to a better understanding of difficult to treat fusion oncoprotein-driven pediatric cancers with limited therapeutic avenues? How well does the project integrate with the mission of the TFCC Program through its potential to reveal a novel drug target or critical dependency for a fusion-driven cancer?

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?

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?

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: To what extent are the project timeline and milestones appropriate and realistic for the proposed research objectives? If applicable, how well does the application address health disparity populations? How well defined are the mechanisms for facilitating sharing of samples and resources consistent with achieving the goals of this program?

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 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.
• 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.
• 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).
• Informing the network about pre-clinical resources available through NIH including drug development capabilities to which the teams 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 U01 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 who 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 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 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, protocols, and procedures for collaborative projects.
• 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]

Keren Witkin, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5371
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.