It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) 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 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The overall goal of this funding opportunity announcement (FOA) and the companion FOA, RFA-CA-17-050, is to establish a network of collaborating investigators to identify and advance research opportunities for translating immunotherapy concepts for children and adolescents with cancer toward clinical applications. The primary goals of this network, the Pediatric Immunotherapy Discovery and Development Network (PI-DDN), will be the discovery of pediatric cancer immunotherapeutic targets, the development of new immunotherapy treatment approaches, and the improved understanding of the immunosuppressive tumor microenvironment to advance new, more effective immune-based therapeutic regimens for high-risk pediatric cancers. This FOA solicits U01 applications for discrete research projects that address relevant research opportunities (e.g., mechanisms of immune evasion, model development, validation of a single target, etc.), while the companion FOA, RFA-CA-17-050, solicits multi-component U54 Center applications.

NCI convened the Blue Ribbon Panel (BRP) in 2016 to provide recommendations for achieving the Cancer Moonshot's ambitious goal of making a decade's worth of progress in cancer research in 5 years, now called the Beau Biden Cancer MoonshotSM Initiative. The BRP was charged with assessing the state of the science in specific areas and identifying major research opportunities that could uniquely benefit from the support of the Cancer Moonshot and could lead to significant advances in our understanding of cancer and in how to intervene in its initiation and progression. The recommendations focused on areas in which a coordinated effort could profoundly accelerate the pace of progress in the fight against cancer and were not intended to replace existing cancer programs, initiatives, and policies already underway. The BRP final report was approved by the National Cancer Advisory Board and included a recommendation for the development of a pediatric immunotherapy translational science network that would facilitate the testing of new immunotherapy approaches in childhood cancer and establish a robust research pipeline to help further advance this field of study. The 21st Century Cures Act was signed into law in December 2016 dedicating new funds to support efforts associated with the Beau Biden Cancer MoonshotSM Initiative, including support for this FOA.

The Pediatric Cancer Working Group of the NCI Cancer Moonshot Blue Ribbon Panel identified pediatric immunotherapy as one of two priorities for acceleration of research advances. There have been major advances in applying immunotherapy for childhood cancers, as illustrated by the high rate of sustained complete responses in children with refractory leukemia using anti-CD19 chimeric antigen receptor (CAR) engineered T cells and by the improvement in survival for children with high-risk neuroblastoma using an anti-GD2 chimeric monoclonal antibody. However, for most patients with high-risk or refractory childhood cancers there are no effective immunotherapy options.

There are several major barriers to fully realizing the potential of immunotherapeutic approaches to successfully treating childhood cancers.

• Childhood cancers typically have low mutation burdens, and thus are much less likely to express neoantigens and hence be susceptible to immune checkpoint blockade therapies. For many childhood cancers, the key genomic alterations are loss of tumor suppressor genes through large chromosomal deletions or the activation of oncogenes through either amplification or through translocations leading to fusion oncoproteins. These fusion proteins appear to have low immunogenicity and, to date, efforts to target them using immunotherapy have been unsuccessful. A very small subset of children with cancer have defects in DNA repair that lead to high tumor mutation burden and responsiveness to immune checkpoint blockade.
  
  
• Most immunotherapeutic strategies (for directly targeting tumor cells) that are in the pipelines of pharmaceutical companies are based on targeting specific antigens expressed on cancers occurring in adults and often have little applicability to childhood cancers. As an example, trastuzumab and ado-trastuzumab emtansine are effective in cancers with HER2 amplification and resulting protein overexpression. However, this genomic alteration is rare in children and hence these agents have no role in the treatment of childhood cancers.
  
  
• Identifying the optimal childhood cancer cell surface antigens for targeting with immunotherapy agents remains a challenge, particularly for pediatric solid tumors. Suitable targets for hematological tumors have been identified and effectively targeted (e.g., CD19-based treatments), but similar advances have not occurred for pediatric solid tumors. While a large body of discovery-based genomic profiling work has been completed, the integration of DNA and RNA sequencing approaches with cellular membrane proteomic profiling to define the proteins that are uniquely and abundantly expressed on pediatric cancers and show little or no expression in normal childhood tissues remains at an early stage. While there are examples of candidate antigens (e.g., MCAM and GPC2) that may serve as novel pediatric cancer-specific immunotherapeutic targets, other candidates can almost certainly be identified with additional effort and resources. A further challenge is that little is known about the proportion of the cell surface proteome that is required for tumor cell maintenance; without this understanding, candidate antigens may be selected for therapeutic targeting for which loss of protein expression leads to rapid resistance. Even with effective immunotherapy targeting CD19, antigen loss is emerging as a challenge that limits durability of remission. Additionally, by using T cells with genetically engineered T cell receptors, there is the potential for targeting intracellular proteins that are processed into peptides and presented at the cell surface in the context of major histocompatibility complex (MHC).
  
  
• A barrier to effective T cell immunotherapy for pediatric solid tumors is that tumors establish a disabling, immunosuppressive tumor microenvironment. Thus, the extended application of immunotherapy to treat a broad range of childhood cancers will not only require identifying novel tumor antigens and targeting T cells to recognize these antigens, but in addition, will require strategies to disrupt the immunosuppressive properties of the tumor microenvironment. Accomplishing this goal will require identifying the distinctive processes used by different cancers to limit anticancer activity and strategies to circumvent these mechanisms.

As a result of the apparent low immunogenicity of pediatric cancers, the therapeutic strategies that are being prioritized for childhood cancers involve engineering antibodies and immune cells to recognize specific non-mutated antigens selectively expressed on these cancers. These approaches include antibody-drug conjugates, bispecific T-cell engaging antibodies, CAR T-cells, and engineered NK cells. They are well advanced for lymphoid malignancies as a result of the ability of patients to tolerate temporary loss of selected lymphoid cells expressing the target antigen of the immunotherapy agent. While the remaining challenge for lymphoid malignancies is to optimize existing effective treatments, the challenge to researchers studying pediatric solid tumors is to identify comparable antigens for these tumors and to then develop effective immunotherapy treatments with acceptable toxicity profiles that target these antigens.

This FOA solicits applications for discrete research projects conducted by teams of investigators with relevant expertise who will work in the context of a collaborative research network, the Pediatric Immunotherapy Discovery and Development Network (PI-DDN), with the goal of identifying and advancing research opportunities for translating immunotherapy concepts for children and adolescents with cancer toward clinical applications. However, the conduct of clinical trials is outside of the scope of the PI-DDN. Each PI-DDN U01 program will address a discrete, relevant pediatric immunotherapy research opportunity.

Potential areas of investigation include but are not limited to:

• Identification of antigenic epitopes that are uniquely and abundantly expressed on childhood and adolescent cancers;
• Development of optimized, highly specific binders for novel pediatric cancer immunotherapy targets;
• Development of candidate novel immunotherapy agents;
• Identification of cancer cell intrinsic and extrinsic mechanisms of immune evasion that limit the effectiveness of immunotherapy interventions against pediatric cancers; and
• Development and application of approaches for in vivo preclinical testing of novel immunotherapy agents, including immunocompetent pediatric cancer models and humanized mouse models.

Multiple Project Director/Principal Investigator (PD/PI) and multi-institutional collaborations are encouraged in order to achieve the breadth of expertise required for a comprehensive approach to pediatric immunotherapy research and to accelerate the pace at which effective immunotherapies are realized for childhood cancers.

Successful applicants will form the PI-DDN, a collaborative research network that will work to advance immunotherapeutic approaches to treat childhood cancers. In addition to completing the research goals outlined in their applications, successful applicants will be expected to work collaboratively with all members of the PI-DDN to share data and resources, discuss shared challenges, and work together to move the field forward.

Applicants are encouraged to contact NCI Staff to discuss the alignment of their proposed work with the goals of this FOA

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

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

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)

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)
• 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 Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) 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.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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 DUNS number and 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 his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

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

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. 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 NOT-OD-11-101).

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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); and
• Number and title of this funding opportunity.

The letter of intent should be sent to:

Judy Mietz, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6250
Email: mietzj@mail.nih.gov

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 FOA.

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.

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

Budget requests must include costs for the PD(s)/PI(s) to attend the initial in-person PI-DDN 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 PI-DDN 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.

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 PI-DDN. Describe how the current concepts, methods, and/or technologies in pediatric immunotherapy will be changed if the Specific Aims are achieved.

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 novel immunotherapeutic strategies for childhood cancers. In addition to standard elements, address the following:

• Explain the importance of the problem or critical barrier to progress in pediatric immunotherapy that the application is trying to address, and why the proposed approach or technology is needed to realize a solution. Critically evaluate existing knowledge and approaches that have been or are being applied in this area of research and specifically describe how the proposed approach will advance the field. The uniqueness of the team, the key milestones, and the expected outcomes of the project, if successful, should be clearly described.
• Project Timeline: A timeline (Gantt chart) including milestones is required for all studies. Milestones are goals that create go/no-go decision points in the project and must include clear and quantitative criteria for success. Yearly quantitative milestones are required in order to provide clear indicators of a project's continued success or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. Milestones and the timeline must be provided in a separate heading at the end of the Approach section.
• 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. The BRP recommendations outline a set of opportunities that, if implemented, will transform our understanding of cancer and result in new opportunities to more effectively prevent and treat the disease, which can reduce the burden of cancer in all Americans and the health disparities that currently exist. Minority health populations and those from urban and rural areas who are poor and medically underserved continue to suffer disproportionately from certain cancers and have higher morbidity and mortality rates.

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, with the following modification: Addressing the Cancer Moonshot Open Access and Data Sharing Policy: Utilizing the provision outlined in the 21st Century Cures Act, NCI has established a data sharing policy for projects that are funded as part of the Beau Biden Cancer MoonshotSM Initiative that requires applicants to submit a Public Access and Data Sharing Plan that: (1) describes their proposed process for making resulting Publications and to the extent possible, the Underlying Primary Data immediately and broadly available to the public upon publication; and (2) if applicable, provides a justification to NCI if such sharing is not possible. NCI will give competitive preference and funding priority to applications that comply with the strategy described here. The data sharing plan will become a term and condition of award.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

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 Policy on Late Application Submission.

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.

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.

It is anticipated that the terms of award will include, but not be limited to, the following:

In carrying out its stewardship of Beau Biden Cancer Moonshot initiatives, the National Cancer Institute (NCI) will monitor and evaluate progress to meet the expectations set forth by Congress in the 21st Century Cures Act. In addition to standard annual Research Performance Progress Report (RPPR) submissions, Principal Investigators may be expected to supply additional progress-related information.

Investigators will be expected to coordinate with and leverage technology from related NCI-sponsored informatics initiatives, in collaboration with NCI program staff. These initiatives include: 1) the NCI Informatics Technology for Cancer Research (ITCR) program, which supports the development of informatics algorithms, tools, and resources across the continuum of cancer research; and 2) the NCI Cancer Research Data Commons, a program that will provide infrastructure to make diverse cancer research data broadly available and to maximize their reuse and impact.

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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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 Component of the SF424(R&R) Application Package. 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 FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number 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 for responsiveness by the NCI. 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.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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).

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.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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 FOA: How well will the project address a problem or critical barrier to fully realizing the potential of immunotherapeutic approaches to successfully treating childhood cancers?

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?

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 FOA: How well does the proposed project represent an innovative concept, technological solution, and/or approach for improving immunotherapy in childhood cancer?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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 children, justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA: 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 appropriate and adequate are the plans for addressing the Cancer Moonshot Public Access and Data Sharing Policy?

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?

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.

For research that involves human subjects but does not involve one of the six 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 six 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.

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 children 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.

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 Animal Section.

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.

Not Applicable

Not Applicable

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.

Not Applicable

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).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

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.

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by CSR, 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:

• 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.
• Will receive a written critique.

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. 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. Programmatic priority will be given to applications with data sharing plan that comply with the NCI Open Access Program for Data and Results from Cancer Moonshot Research.

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.

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 grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. 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 FOA 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.

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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 FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Part 75, 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 awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH 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 awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• 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 for the performance and proper conduct of the research and administrative functions supported under this Funding Opportunity Announcement 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 PI-DDN investigators, and one another to maximize impact of the PI-DDN and meet Program goals and objectives.
• Serving as voting members of the PI-DDN Steering Committee (PI-DDN SC or SC) that is responsible for governance of PI-DDN activities (as described below).
• Accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the PI-DDN SC.
• Maintaining the confidentiality of the information developed or handled by the PI-DDN, including, without limitation, unpublished data, protocols, data analysis, confidential exchanges between members of the PI-DDN, 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 in a timely manner. All PDs/PIs are expected to share data and resources generated through this award in accordance with the approved plan for making quality-assured data and materials available to the scientific community and the NIH as written in the final version of the grant application, and consistent with sharing policies and recommendations developed and approved by the SC, NIH sharing policies, and the goals of the FOA.
• Ensuring that any industry collaborations should be governed by a 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.
• Complying with OHRP and FDA regulations concerning protection of human subjects if the project involves human subjects and/or NIH-defined clinical research.
• All PDs/PIs must operate in accordance with processes and goals as delineated in the Funding Opportunity Announcement.
• Operating in accordance with processes, goals, and policies established by the SC to the extent of applicable grant regulations.
• Attending an initial face-to-face Kickoff Meeting of the PI-DDN PDs/PIs, followed by at least one PI-DDN investigator meeting annually.
• Adhering to a Network Communication Plan: A consensus Communication Plan will be drafted by the PI-DDN SC during the kickoff meeting of the PI-DDN. This plan will clearly spell out interactive requirements that all PI-DDN investigators are expected to follow, including:
• Participation in regular conference calls with fellow PI-DDN colleagues through contribution to various sub-committees and working groups;
• Participation and presentation of findings at the PI-DDN Annual Investigators' Meeting;
• Coordination of efforts with other members of the PI-DDN; and
• Jointly publishing on PI-DDN collaborations in a timely manner.
• In carrying out its stewardship of Beau Biden Cancer Moonshot initiatives, the NCI will monitor and evaluate progress to meet the expectations set forth by Congress in the 21st Century Cures Act. In addition to standard annual Research Performance Progress Report (RPPR) submissions, PDs/PIs may be expected to supply additional progress-related information.
• Awardees 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 HHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

An NCI Program Director acting as Program Officer will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Additionally, designated NCI Program Director(s) serving as a Project Scientist(s) will be involved in assisting and coordinating interactions and collaborations among the various investigators and any industrial partners and will ensure access to other NIH relevant programs.

Specific activities of substantially involved NCI staff members will include:

• Advising the awardees on specific scientific issues as well as programmatic priorities;
• Facilitating access to drug development capabilities and other resources available through NCI to which the teams may have access;
• Co-organizing and participating in PI-DDN SC meetings;
• Assisting in the management of the PI-DDN SC including the development of draft sharing and operating policies that are in accordance with NIH guidelines;
• Reviewing the compliance of PI-DDN awardees with the recommendations developed by the SC; and
• Coordinating external evaluation of the PI-DDN.

The NCI reserves the right to terminate any PI-DDN 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 PI-DDN policies and procedures; (3) substantive changes in the management of the PI-DDN award that are not in keeping with the objectives of the FOA; and/or (4) failure to make substantial progress towards milestones keeping in mind the agreed upon go/no-go decisions.

Areas of Joint Responsibility include:

The PI-DDN Steering Committee (PI-DDN SC or SC). The SC will be the main governing body for the PI-DDN that is responsible for governance of PI-DDN activities as described below.

The PI-DDN SC will consist of the following voting members:

• Two representative PD(s)/PI(s) of each PI-DDN Center or a PD/PI and a designated senior investigator) who will have one vote each; and
• The NCI Project Scientists for the PI-DDN Centers will have one vote in total.

Additional NIH staff members may participate in SC meetings as non-voting members as needed (for example to provide additional expertise).

Additional non-voting members to serve in an advisory capacity may be added to the SC as needed by a decision of the existing voting committee members.

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

The PI-DDN SC will be constituted at the initial PI-DDN meeting and will meet regularly (monthly or quarterly), including at least once in-person during the annual PI-DDN Investigators' Meeting. Operating procedures for the SC will be established at the Consortium Kickoff Meeting.

The chair of the PI-DDN SC will be selected from the representatives of all awardees and is responsible for coordinating the PI-DDN activities, preparing meeting agendas, and chairing SC meetings. At the end of 1 year of service, the SC may ask the Chairperson to serve a second 1-year term, or choose a replacement for that role. The SC may also choose to replace the PI-DDN SC chairperson at any time based on poor job performance or failure to follow the relevant procedures and guidelines.

All major scientific and policy decisions will be determined by voting policies as established by the PI-DDN SC.

Steering Committee responsibilities will include the following:

• Developing collaborative protocols Network policies;
• Identifying impediments to success and strategies to overcome them;
• Developing shared tools for disseminating information about PI-DDN;
• Discussing important issues relevant to immunotherapeutic approaches in childhood cancer;
• Helping with the planning of major events (such as the annual meeting);
• Identifying opportunities for sharing techniques, materials, information and tools developed within each individual PI-DDN Center;
• Facilitating communication and fostering collaboration across the PI-DDN;
• Reviewing progress of the PI-DDN towards meeting the overall Network goals;
• Developing publication policies to facilitate collaborations and co-publications by PI-DDN members;
• Ensuring the PI-DDN leverages existing NIH resources and programs;
• Evaluating collaborative activities, and providing feedback to the NCI Program Staff; and
• Discussing implementation of recommendations or suggestions from the NCI and any external consultants and plan a timely implementation strategy.

Dispute Resolution:

Disagreements that may arise in scientific/technical matters, publication/authorship matters or programmatic matters (within the scope of the award) between award recipients, or between award recipients and the NCI, may be brought to arbitration after first attempting to resolve the issue through the PI-DDN SC or its subcommittees, as appropriate. An Arbitration Panel composed of three members will be convened. The Panel will be composed of: a designee of the PI-DDN SC chosen without NCI staff voting, one NCI designee, and a third designee with expertise in the relevant area who is chosen by the other two members; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure in no way affects the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.

When multiple years are involved, awardees 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.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees 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 Award Term and Conditions for Recipient Integrity and Performance Matters.

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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Nita Seibel, M.D.
National Cancer Institute (NCI)
Telephone: 240-276- 6560
Email: seibelnl@mail.nih.gov

Judy Mietz, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6250
Email: mietzj@mail.nih.gov

Syed Quadri, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-435-1211
Email: quadris@mail.nih.gov

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: wolfreyc@mail.nih.gov

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.