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

This funding opportunity announcement (FOA) will expand an Immuno-Oncology Translation Network (IOTN) with the overall goal of accelerating research advances through collaborative team science approaches to improve immunotherapy outcomes for diverse adult cancers that are either resistant or develop resistance to immunotherapies. Specifically, this strategy is expected to discover new immune targets and evaluate novel immune-based therapies and combination approaches that eliminate established cancers in adults or to prevent cancers before they occur.

Currently, the IOTN is composed of:

• Ten U01 Cancer Immunotherapy Research Projects (supported by RFA-CA-17-045);
• Two U01 Cancer Immunoprevention Research Projects (supported by RFA-CA-17-046);
• One U24 Data Management and Resource-Sharing Center (DMRC) (supported by RFA-CA-17-047); and
• One U24 Cellular Immunotherapy Data Resource (CIDR)(supported by RFA-CA-17-048) 

An expansion of the existing IOTN framework will include the following components:

• UG3/UH3 Cancer Immunoprevention Phased Award Projects (to be supported by this FOA, RFA-CA-19-012.
• U54 Immuno-engineering to Improve Immunotherapy (i3) Centers: (to be supported by RFA-CA-19-013)
• Additional U01 Cancer Immunoprevention Research Projects (to be supported by RFA-CA-19-014); and
• Additional U01 Cancer Immunotherapy Research Projects (to be supported by RFA-CA-19-015).

The purpose of this FOA is to support UG3/UH3 Cancer Immunoprevention Phased Award Projects. Applicants responding to this FOA must apply for both the UG3 and UH3 phases together in a single application. Exploratory studies aimed at immune target identification and validation will be supported under UG3. Achievement of the UG3 milestones will be necessary for transition to the UH3 Implementation Phase. UH3 phase may be awarded after administrative review of the UG3 milestones. Provided these milestones are achieved, UH3 phase may continue with development and preclinical testing of specific interventions.

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 establishing a translational science network devoted exclusively to discovering and evaluating novel immune-based approaches to treat and prevent adult cancers. Implementation of the IOTN will address this BRP scientific priority. 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.

Currently the investment in cancer immunoprevention research is minimal. From the pharmaceutical industry perspective, this may reflect the lack of a clear market for preventive vs. therapeutic vaccines. From a scientific point of view, preventive vaccines may have important advantages. Vaccination may trigger a more effective immune response in healthy individuals with normal immune systems compared to cancer patients with a large tumor burden and an immunosuppressive microenvironment. Features of the microenvironment are also likely to be distinctly different and more favorable in newly emerging pre-malignant lesions. Little is currently known about the time-course for appearance of immune targets during the carcinogenic process or the best way to stimulate immunity. The potential for controlling the induced immune response is increasing with the advent of new adjuvants. This is likely to continue in the future. The National Institute of Allergy and Infectious Diseases (NIAID) has funded a major effort to discover and develop new adjuvants. Genomic analyses have been useful in defining patterns of mutations occurring in established tumors, and this will be extended in the future to include pre-malignant lesions. Immunologists have devised strategies for overcoming tolerance to tumor-associated self-antigens such as use of fusion proteins that enhance immunogenicity, a focus on sub-dominant epitopes, and use of enhancer molecules with vaccine peptides.

The Immuno-Oncology Translational Network is designed to accelerate research on cancer immunotherapy and is expected to provide a synergistic environment for all IOTN awardees.

Cancer Immunoprevention Phased Award Projects proposed in response to this FOA should be designed to identify the earliest exploitable changes in the carcinogenic process and develop immune-based interventions.

High-Risk Cohorts for Cancer-Immunoprevention Studies

These Phased Award Projects are expected to focus on cancers that occur in specific organ sites in high-risk sub-populations. Examples of at-risk sub-populations that applicants may consider include but are not limited to those listed below.

• Genetically Predisposed Individuals
• Lynch Syndrome
• BRCA1/2 Carriers
• Familial Adenomatous Polyposis (FAP)
• Neurofibromatosis and Tuberous Sclerosis Complex (neurologic and other cancers)
• Li-Fraumeni, Fanconi's Anemia, Dyskeratosis Congenita and syndromes that are more rare, but with well-defined genetics and biology
• Patients with Diagnosed Premalignancies such as:
• Low-grade lesions of the prostate (Gleason Score 6)
• Colon Polyps
• Ductal Carcinoma In Situ (DCIS)
• Oral Leucoplakia
• Barrett's Esophagus
• Monoclonal Gammopathies of Undetermined Significance (MGUS)
• Environmentally or Occupationally Exposed Individuals
• Asbestos Workers
• Smokers

Animal Models

Animal models that phenocopy the human disease may be employed with the goal of identifying actionable targets arising in pre-cancerous lesions and evaluating whether the immune system can target these earliest cellular changes to inform early intervention (prevention) approaches. In contrast to immunotherapy, where malignant tumors have already grown and evolved at the molecular level, establishing a complex and immunosuppressive microenvironment, early intervention may directly intercept and eradicate emerging premalignant clones. Identification of exploitable immune targets in these earliest lesions could ultimately be the basis for vaccines applied to prevent adult tumors. Lynch syndrome provides a model for this process. In Lynch syndrome, inheritance of one allele of a mutant DNA mismatch repair gene predisposes an individual to colon and endometrial cancers. Acquisition of a mutation in the remaining normal allele constitutes a "second hit" that destabilizes the genome and leads to the emergence of premalignant clones. Since the mismatch repair defect preferentially results in deletions or insertions at coding microsatellite regions of the genome, recurrent frame-shift mutations, which can be detected and confirmed by whole-genome or -exome and transcriptome sequencing (e.g., RNA-seq), can be the basis for a preventive vaccine target. Results of mechanism-directed interventions in this and other high-risk cohorts may enable expansion of vaccine approaches to average-risk cohorts and common solid tumors.

Scientific Goals of the Cancer Immunoprevention Phased Award Projects

While the principal intent of this FOA is to address primary cancer prevention, applications directed toward immunoprevention of progression of premalignant lesions (e.g., adenomas of the colon as seen in Familial Polyposis or progression of benign neurofibromas to malignant tumors) will be considered under this FOA. Studies should be pre-clinical with the potential for translating the findings into clinical interventions in the future. The main characteristics and overall goals of the Cancer Immunoprevention Project are summarized below.

Two-phase Projects

Investigators responding to this FOA must address plans for both the UG3 and UH3 phases in a single application as described below. The UG3 phase (up to 2 years in duration) will be a milestone-driven pilot/innovation phase aimed at 1) discovering and 2) validating immune targets with potential for development of immunopreventive interventions.

Upon successful completion of these milestones, the project may transition to the UH3 phase (up to 3 years in duration with a total project period of 5 years) focusing on development and preclinical testing of interventions. 

Objectives for UG3 Planning-Exploratory Phase:

Phase 1 (UG3) The UG3 phase should include the following types of research activities:

• Define an experimental setting that enables the definition of changes in potential immune targets as a function of time during carcinogenesis. Approaches may be based on classical models of cancer initiation and progression or de novo models. Models should reflect biology inherent to high-risk clinical cohorts who could be the population targeted for prevention (translational studies).
• Evaluate the validity of identified targets for immunoprevention as a function of time. This may involve genetic or pharmacologic manipulations of the target. A clear distinction between validation for treatment vs. prevention should be maintained. For example, the earliest changes may be hypothesized to be most important for prevention and not for treatment.

Objectives for UH3 Implementation Phase:

The Phase 2 of the proposed project must be based on results to be obtained during Phase 1. The goals for the Phase 2 may include the following aspects:

• Develop interventions for the target identified in UG3 Phase that would have practical potential for the future translational studies. These may be vaccine strategies or other interventions that address immune targets.
• Produce the preclinical reagents necessary for demonstration of cancer preventive efficacy. Where animal models are utilized, consideration should be given to species-specific issues for clinical translation.
• Demonstrate and reproduce preventive efficacy in preclinical models. Multiple models should be utilized with careful attention to evidence of toxicity in experimental animals.

Transition from the UG3 to the UH3 phase:

An initial cooperative agreement award for up to 2 years will be made for the UG3 phase.

Prior to the end of the UG3 phase, NIH program staff will review the progress towards the UH3 phase.

Criteria to determine whether the award will transition from the UG3 phase to the UH3 phase will include: 

• Successful completion of established milestones during the UG3 period of the project.
• Demonstration of the feasibility of interventions planned for the UH3 phase.
• Extent to which UG3 pilot/innovation phase activities support the aims of the UH3 phase.

Note: It is anticipated that not all funded projects in the UG3 Planning-Exploratory Phase will be approved for transition to the UH3 Implementation Phase.

Future Continuation Beyond the UG3/UH3 Scope. Immunoprevention concepts emerging from Cancer Immunoprevention Phased Award Projects are expected to be explored further beyond the scope of this FOA and the UH3 stage.

In this context, prospective applicants are encouraged to consider other suitable NCI-supported resources. In particular, UG3/UH3 projects may be designed in such a way that they expansion can go through the PREVENT Cancer Preclinical Drug Development Program (PREVENT). The PREVENT pipeline (operated by the National Cancer Institute's Division of Cancer Prevention, DCP) offers the full range of preclinical development resources including: animal efficacy testing, vaccine optimization, cGMP vaccine production, toxicology testing and support for preparation of INDAs for filing with the FDA. DCP also conducts early-stage clinical trials for preventive interventions including vaccines.

Whereas the use of the PREVENT pipeline is encouraged, it is not required. Accordingly, investigators considering post-UH3 development will be able pursue any setup suiting their needs (e.g., a partnership with biomedical industry.)

Non-responsive Studies

The following types of studies are beyond the scope of this FOA and will be considered non-responsive (non-responsive applications will not be reviewed):

• Applications which address immunotherapy of established cancers. Such projects may be responsive to the companion FOA for Cancer Immunotherapy Research Projects (RFA-CA-19-015).
• Projects proposing studies that meet the current NIH definition of clinical trials.

Governance of the IOTN: The IOTN components will be governed by the IOTN Steering Committee. (see Section VI: Terms and Conditions of Cooperative Agreement.)

Evaluation of the Program: IOTN awardees will be expected to participate in an external evaluation process of the IOTN program coordinated by NCI Program Staff (see Section VI: Terms and Conditions of Cooperative Agreement.)

Applicants are encouraged to reach out to the Scientific/Research Contact listed in Section VII. Agency Contacts to ensure appropriate alignment of projects with available funding opportunities.

A technical assistance webinar will be held for potential applicants from 12:00 - 1:00 pm (EST) on Tuesday, November 13, 2018. NIH staff will be available to answer questions related to this and companion FOAs. 

To join the webinar, pre-registration is required through WebEx. Webinar information will be provided upon pre-registration at the following link: Register.

Potential applicants are encouraged to submit questions by November 12 to NCIIOTN@mail.nih.gov.

Slides will be available on the Division of Cancer Biology webpage two days following the completion of the webinar.

Participation in this webinar, although encouraged, is optional and is not required for the submission of an application.

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 from 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
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

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) 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, 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)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Robert H. Shoemaker, Ph.D.
National Cancer Institute
Telephone: 240-276-7077
Email: Shoemakr@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.

Any individual designated as a PD/PI must commit a minimum of 1.2 person-months effort per year to the project. This minimal effort level must be maintained during the entire project period.

Applicants must budget for travel and per diem expenses for Steering Committee meetings. In the first year, applicants should plan for at least two senior investigators (all PDs/PIs, if desirable, or the PD/PI and a senior investigator if multi-PD(s)/PI(s) option is not used), to attend a Planning Meeting and one Steering Committee Meeting. In the second and subsequent years, applicants should plan for at least two senior investigators (all PDs/PIs, if desirable, or the PD/PI and a senior investigator if multi-PD(s)/PI(s) option is not used) to attend one Steering Committee meeting per year.

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: Provide the overall goals for the entire application and indicate separately Specific Aims to be accomplished in the UG3 Planning-Exploratory Phase and the UH3 Implementation Phase.

Research Strategy: Organize the Research Strategy into the subsections identified below.

Sub-section A. Background and Significance

Define the high-risk cohort that will be the subject of this research and the rationale for selection. Provide a vision for how an immunopreventive intervention might be implemented in the future.

Preliminary data are not required for this application. However, if preliminary data are available, they may be included in this sub-section.

Sub-section B. Approach (must be divided into the UG3 Planning-Exploratory Phase and the UH3 Implementation Phase):

UG3 Planning-Exploratory Phase--address each of the items listed below.

• Description of proposed experimental setting for conduct of the research. Provide a rationale for how this setting can support identification of targets for immune interventions.
• Describe plan for establishing the validity of targets.
• Plans for transition to the UH3 Implementation Phase.

UH3 Implementation Phase--address each of the items listed below.

• Plans for development of interventions based on targets identified in the UG3 Phase.
• Plans for production or acquisition of reagents necessary for development of interventions.
• Demonstration of preclinical cancer preventive efficacy.

Health Disparities. If applicable to the type of research being proposed, address how health disparity populations or data will be integrated into the proposed studies. Highlight, as relevant, any opportunities that, if implemented, can reduce the burden of cancer in the health disparities that currently exist. In this context, efforts are encouraged to address the needs of racially/ethnically diverse populations and those from urban and rural areas who are poor and medically underserved, who continue to suffer disproportionately from certain cancers and have higher morbidity and mortality rates.

Sub-section C. Milestones and Timelines

Using separate sub-headings, provide detailed timelines and milestones that are aligned with objectives of each phase:

• Milestones for UG3 Planning-Exploratory Phase (including specific milestones that will serve as criteria for progressing to the UH3 Implementation Phase); and
• Milestones for UH3 Implementation Phase.

The description of milestones for each phase must include objective criteria for determining whether a milestone has been achieved.

In addition, outline the anticipated steps/activities for the future expansion of the project beyond the UH3 phase.

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:

• All applications, regardless of the amount of direct costs requested for any one year, should addressa Data Sharing Plan.
• Addressing the Cancer Moonshot Public Access Pilot Program: Utilizing the provision outlined in the 21st Century Cures Act, NCI has established a data sharing policy for projects that are funded aspart 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 resultingPublications and to the extent possible, the Underlying Primary Data immediately and broadly available to the public 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 with a data sharing plan that complies with the strategy described here. The data sharing plan will become a term and condition of award.
• Guiding Principles for Cancer Moonshot Biobanking Activities: The goal in developing these guiding principles is to accelerate research by a) increasing the availability of biospecimens for Cancer Moonshot-related and other biomedical research through facilitation of investigator to investigator sharing of biospecimens, and b) increasing the reproducibility of Cancer Moonshot research through improved biospecimen practices and corresponding annotation. These guiding principles also seek to facilitate, where possible, increased engagement of research participants through researchers' communication of aggregate research results and, in some cases, individual genomic findings that may be medically actionable for research participants. NCI will give competitive preference and funding priority to applications that conform to the "Guiding Principles for Cancer Moonshot Biobanking Activities" (http://biospecimens.cancer.gov/programs/cancermoonshot/principles) and are consistent with the "2016 NCI Best Practices for Biospecimen Resources"

Appendix:

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

When involving NIH-defined human subjects research, clinical research, and/or 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.

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.

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 responsiveness by the 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. Any instructions provided here are in addition to the instructions 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 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?

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?

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? 

Specific to this FOA:

• How well are the high-risk cohorts addressed by this application defined?
• Has a clear path to clinical translation been described?
• As described, how feasible is the plan for immune target identification?
• What is the potential for mechanism-based cancer preventive intervention development in the UH3 Phase?

Milestones:

• How clearly are the steps and milestones defined?
• How feasible and quantifiable are the milestones with respect to proposed objectives?
• How adequate are the criteria provided for the UG3 Phase to determine successful completion of milestones?
• Are the milestones for the UH3 Phase appropriate to allow for future project expansion?

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?

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 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.

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.

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 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:

• 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 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 appropriate national Advisory Council or 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.

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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/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. 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 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, 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:

• Defining objectives and approaches, and to ensure scientific rigor in the planning, conducting, analyzing, and publishing of results, interpretations, and conclusions of studies conducted underthis program;
• Setting project milestones in consultation with NIH staff, and reporting progress and objectives to NIH staff;
• Coordinating efforts and cooperating with the other U01 and U24 components of the IOTN and withIC Project Scientists. These actions may involve (but will not be limited to) participation in appropriate coordinating meetings and/or working groups, and/or teleconferences as needed;
• Overseeing the implementation of an approved data sharing plan and resource sharing plan. Institutions/organizations participating in the Consortium will be expected to share with each other knowledge, data, research materials, and any other resources necessary and relevant to the IOTN consortium;
• Leveraging, where feasible, technology from related NCI-sponsored informatics initiatives, for example 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;
• Coordinating with and leveraging, where feasible, the technology of 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 (cbiit.cancer.gov/cancerdatacommons);
• Maintaining the confidentiality of the information shared by the IOTN consortium, including, without limitation, unpublished data, protocols, data analysis, confidential exchanges between members of the IOTN consortium, as well as any confidential information received by third party collaborators;
• Annotating samples through the use of Consortium-defined Common Data Elements (CDEs) .Participating and presenting findings at annual grantee meetings convened by NIH IC Project Scientists through the DMRC;
• Adhering to a Consortium Communication Plan: A consensus Communication Plan will be drafted by the Steering Committee during the Kickoff Meeting of the IOTN Consortium. This plan will clearly spell out interactive requirements that all IOTN Consortium PD(s)/PI(s) are expected to follow, including:
• Participating in regular conference calls and contributing to various sub-committees and working groups;
• Participating and presenting findings at IOTN annual investigator meetings; and
• Coordinating efforts with other members of the IOTN consortium.
• Meeting yearly milestones as defined by PD(s)/PI(s) and NIH IC Project Scientists at the time of award;
• Working with, and cooperatively interacting with, and actively seeking input from NIH IC Project Scientists;
• Participating in NCI-coordinated evaluation of the IOTN program.

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 DHHS, PHS, and NIH policies. IOTN PD(s) are also encouraged to organize and participate in collaborative activities and scientific or programmatic working groups.

In carrying out its stewardship of Beau Biden Cancer Moonshot initiatives, the NIH Project Scientists will monitor and evaluate progress toward meeting 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.

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

Designated Program Director(s) from NCI and other NIH Institutes supporting this initiative will have substantial involvement as Project Scientists. Additionally, a Program Director from NCI (or another appropriate NIH Institute), acting as Program Official, will be responsible for the normal, scientific and programmatic stewardship of the award and will be named in the award notice.

In carrying out its stewardship of Beau Biden Cancer Moonshot initiatives, the NCI staff members will monitor and evaluate progress to meet the expectations set forth by Congress in the 21st Century Cures Act.

Activities of substantially involved staff members from NCI and other NIH Institutes involved will include:

• Coordinating and facilitating interactions among the activities awarded under this initiative;
• Working closely with investigators on research projects to facilitate interactions/collaborations between U24 and U01 awardees across the consortium;
• Assisting the awardees as a resource in facilitating their broader interactions with other NCI and NIH programs for the purpose of leveraging and coordinating existing NIH/NCI resources and infrastructures, such as those within the NCI ITCR program and the NCI Cancer Research Data

Commons;

• Assisting in avoiding unwarranted duplication of effort with other NCI efforts;
• Suggesting reprogramming efforts, including options to modify projects/programs when certain objectives of this FOA are not met -- specifically, the NIH IC Project Scientists may recommend withholding of support, suspension, or termination of an award for lack of adherence to required

IOTN Consortium policies and/or procedures;

• Developing working groups and trans-project efforts as needed; and
• Monitoring progress and direction of awardees and working groups as needed;
• Organizing and conducting regular meetings, as needed, to share progress between the U01 and
• U24 awardees of the IOTN Consortium either by teleconference, videoconference, or face-to-face nteraction.

The NCI reserves the right to reduce the budget or withhold an award in the event of substantial awardee underperformance or other substantial failure to comply with the terms of award.

Areas of Joint Responsibility include:

A Steering Committee (SC) will serve as the main governing board of the IOTN program as described below.

Awardees will join an existing IOTN Steering Committee (SC) which will continue to serve as the main governing board of the IOTN program as described below.

Awardees added as voting members to the existing IOTN SC include:

• One representative from each new U01, U54, and UH2/UH3 award (a PD/PI or their designee) who will have one vote; and
• Other PD(s)/PI(s) can participate in SC meetings as non-voting members according to established IOTN Steering Committee bylaws;  

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

• Conducting monthly teleconference meetings;
• Establishing IOTN consortium policies, procedures, and guidelines;
• Establishing policies and procedures for collaborative projects and protocols;
• Developing guidelines for the collection and distribution of specimen reference sets for collaborative research;
• Identifying impediments to success and developing strategies to overcome them;
• Serving as a nucleus for a broader outreach to the entire extramural immuno-oncology research community;
• Organizing agendas for annual Steering Committee meetings;
• All major scientific and policy decisions will be determined by voting policies as established by the SC. Developing shared tools for disseminating information about the IOTN consortium; and
• The SC may decide to establish sub-committees for specific purposes and NIH IC Project Scientists will serve on such sub-committees, as they deem appropriate.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award 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 awardee. This special dispute resolution procedure does not alter the awardee'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.

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, application errors and warnings, documenting system problems that threaten on-time submission, and 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)

General Grants Information (Questions regarding application processes and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Robert H. Shoemaker, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-7077
Email: Shoemakr@mail.nih.gov

Referral Officer
National Cancer Institute
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: Crystal.wolfrey@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.