Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute of Environmental Health Sciences (NIEHS)
National Institute of Neurological Disorders and Stroke (NINDS)

Funding Opportunity Title

Immuno-Oncology Translation Network (IOTN): Cancer Immunotherapy Research Projects (U01 Clinical Trial Not Allowed)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

Reissue of RFA-CA-17-045

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-CA-19-015

Companion Funding Opportunity

RFA-CA-19-012, UG3/UH3 Phase Innovation Awards Cooperative Agreements

RFA-CA-19-013, U54 Specialized Center- Cooperative Agreements

RFA-CA-19-014, U01 Research Project – Cooperative Agreements

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.353, 93.273, 93.855, 93.121, 93.113, 93.853

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) is associated with the Beau Biden Cancer MoonshotSM Initiative that is intended to accelerate cancer research. Specifically, this FOA targets the following area designated as scientific priority by the Blue Ribbon Panel (BRP): Recommendation B. Create a translational science network devoted exclusively to immunotherapy approaches to treat and prevent adult cancers. 

The purpose of this FOA is to expand organ site-specific Cancer Immunotherapy Research Projects as components of the Immuno-Oncology Translation Network (IOTN). The IOTN will form an integrated network of multi-disciplinary, collaborative teams with the overarching goals of accelerating translational research of innate and adaptive immune mechanisms that contribute to tumor progression, and evaluating new or improved immunotherapeutic strategies (including combinations with standard or other therapies) that result in durable anti-cancer responses. Studies should be largely pre-clinical involving clinically-relevant models and endpoints.

Key Dates
Posted Date

October 31, 2018

Open Date (Earliest Submission Date)

January 8, 2019

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

February 8, 2019, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

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

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

April/May 2019

Advisory Council Review

August 2019

Earliest Start Date

September 2019

Expiration Date

February 9, 2019  

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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.


There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
  4. Table of Contents

    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

    Part 2. Full Text of Announcement
    Section I. Funding Opportunity Description
    Purpose

    This funding opportunity announcement (FOA) will expand the Immuno-Oncology Translation Network (IOTN) which has the overall goal of accelerating research advances through collaborative team science approaches to prevent cancers before they occur, or 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.

    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:

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

    The purpose of this specific FOA is to re-issue RFA-CA-17-045 to support additional Cancer Immunotherapy Research Projects.

    Background

    NCI convened the Blue Ribbon Panel (BRP) in 2016 to provide recommendations for achieving the Cancer Moonshot's goal of accelerating progress in cancer research, 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. 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.

    It is expected that research proposed in response to this FOA will engage a pool of scientists from diverse backgrounds, including those from underrepresented groups. In line with NIH-wide policies (NOT-OD-18-129), fostering diversity and addressing underrepresentation in the scientific research workforce is one of the key components of the NCI strategy to facilitate scientific discovery and enhance innovation.

    Scientific Scope of the Organ Site-Specific Cancer Immunotherapy Research Projects

    The immune system has the ability to recognize and eliminate cancers. Immunotherapy approaches, such as cancer vaccines, checkpoint blockade, engineered T cells, genetically-modified viruses, and bispecific T cell engagers, that exploit this capability have produced durable, long-term survival in animal models and some patients. However, not all tumors are equally sensitive to immune control. The principal impediments to immune elimination of both "hot" and "cold" tumors are intrinsic resistance mechanisms and an immunosuppressive tumor microenvironment. In addition, adaptive immunity and acquired resistance following successful immunotherapy have also been reported. Further, immune-related adverse events (irAEs) are increasingly being reported as another barrier to the efficacy of immunotherapy in the clinic.

    Tumors which have an inflammatory tumor microenvironment and are heavily infiltrated by effector T cells are considered "hot" tumors and often respond better to checkpoint blockade immunotherapy compared with non-inflamed or “cold” tumors. One of the significant needs is to identify what distinguishes “hot” tumors that respond to immunotherapy from “hot” tumors that fail to respond or “cold” tumors that show little responsiveness.

    The overarching goal of the organ site-specific Cancer Immunotherapy Research Projects is to conduct systematic and comprehensive investigation of host immune cell-tumor cell interactions across multiple human cancers, including both “hot” and “cold” cancers, to define how tumor cells recruit and alter immune cell function to generate immunosuppressive tumor-promoting environments, and identify how to reprogram immune cells or the cancer microenvironment to promote anti-tumor immune responses. The IOTN framework will provide a foundation for enabling rapid translation of basic and pre-clinical discoveries by investigators through fostering highly-collaborative approaches among IOTN-funded investigators and between IOTN-funded investigators and existing NCI-supported research communities.

    The purpose of this FOA is to support an integrated network of multi-disciplinary, collaborative teams to accelerate translational research and maximize future clinical benefits by:

    • Investigating the innate and adaptive immune mechanisms contributing to tumor progression or limited responses to anti-cancer interventions, including immunotherapies
    • Discovering and evaluating new or improved immunotherapeutic strategies (including combinations with standard or other therapies) resulting in durable anti-cancer responses with minimal adverse events.

    Specifically, the goal is to improve cancer treatment with immune-based approaches by enhancing our understanding of factors that contribute to immunosuppression, including within the immune cells, tumor cells, or tumor microenvironments. Scientific interests of the NCI and partnering NIH Institutes, the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute of Environmental Health Sciences (NIEHS), and the National Institute of Neurological Disorders and Stroke (NINDS), in specific cancer sites are delineated below:

    NCI

    The NCI solicits applications that have the potential to identify and advance highly-effective immunotherapy approaches (including combination approaches with standard or other cancer therapies) into future clinical application across all major human cancers. Applications that align with cancers prioritized by the Cancer Moonshot Human Tumor Atlas initiative (ovarian, prostate, breast, colorectal and lung cancers) are specifically requested to foster synergy and accelerate the pace of discovery within the Cancer Moonshot program. However, highly-meritorious applications focused on other organ sites, including pancreatic cancer and cancers such as multiple myeloma, cervical cancer, gastric cancer, and non-alcoholic steatohepatitis that are prevalent in ethnic minority or underserved populations, are also encouraged.

    Ovarian cancers are characterized by an extremely immunosuppressed microenvironment, and not surprisingly show limited responses (<15%) to currently available immunotherapies. Although dendritic cells are robustly recruited to ovarian cancers, multiple secreted factors enriched in ovarian cancers conspire to blunt the antigen presentation function of these cells.

    The precise mechanisms underlying the lack of responsiveness to immunotherapy in prostate cancers have not been identified. The large degree of heterogeneity within the tumors along with dynamic expression of newly identified immune checkpoints further complicate the choice of treatment options involving immunotherapy.

    Only a subset of breast cancers is responsive to immunotherapy. Triple negative breast cancer (TNBC), which accounts for 15-20% of all breast cancers, has shown a 12-19% objective response rate to inhibitors of programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1). Whereas extensive tumor-infiltrating lymphocytes are observed in TNBC, the remaining >80% of non-TNBC show relatively poor infiltration of cytotoxic T-cells, increased numbers of immunosuppressive regulatory T cells and myeloid-derived suppressor cells that have been linked to poor survival.

    Analogous to breast cancers, only 15% of colorectal cancers (CRC) respond to immunotherapy. Microsatellite instability (MSI)-high CRC, characterized by mismatch repair deficiency and a high mutational load, are more responsive to immunotherapy. As the frequency of this phenotype diminishes to 4% with advanced stages of CRC, there is an urgent need for additional approaches to improve susceptibility of MSI-low or microsatellite-stable CRC to immunotherapy.

    In contrast to the immunologically “cold” tumors, lung cancers, particularly non-small-cell lung cancers (NSCLC), display relatively stronger responses to checkpoint blockade but present additional challenges for durable effective immunotherapy. Whereas the high mutational loads and neoantigen expression in NSCLC are linked to robust immune cell infiltration and initial responses, tumor cells may escape immune surveillance through both genetic and epigenetic mechanisms including exhaustion of tumor-infiltrating T cells.

    Thus, each of these prioritized organ sites represents unique challenges for maximizing the therapeutic potential of immunotherapy.

    NIAAA and NCI

    The International Agency for Research on Cancer reports that cancers of the upper aerodigestive tract, including oral cavity, pharynx, larynx and esophagus, are related to alcohol consumption, as are cancers of the colon, breast, and liver. Specific mutations in alcohol metabolizing enzymes correlate strongly with esophageal cancer incidence. Alcohol exposure is a major risk factor for hepatocellular carcinoma. While failure of immune surveillance has been reported in some preclinical alcohol-associated cancer models, many questions remain for site-specific tumor environments. The NIAAA solicits applications that have the potential to identify the role played by alcohol use on intrinsic resistance mechanisms and generation of an immunosuppressive tumor microenvironment that influence alcohol-induced cancers, and to accelerate the development of guidelines to improve outcomes of immunotherapy for these forms of cancer.

    NIAID and NCI

    NIAID is interested in applications that propose to: identify innate and adaptive immune mechanisms that can be manipulated to reduce immune-related adverse events (irAEs); evaluate host factors (e.g., genetics, epigenetics) associated with the risk of developing irAEs; and identify new immune targets for immunotherapy and their mechanism of action.

    NIDCR and NCI

    Head and Neck Cancers: Advances in our understanding of the role the immune system plays in the development of Head and Neck Squamous Cell Carcinomas (HNSCC) has offered promising opportunities for immunotherapeutic intervention to improve survival and reduce morbidity associated with the disease. Immune evasion and dysregulation are associated with the initiation and progression of HNSCC. HPV-negative HNSCC are characterized by high mutational burden and a markedly worse prognosis. The rich neoantigen landscape suggests an increased immunogenicity that could respond to immune-modulating therapies. Recent preliminary clinical reports have shown immune PD-1 checkpoint inhibitor to have promising activity in HNSCC. However, the response rates are still low, in the range of 12-20%. Both HPV-positive and HPV-negative HNSCC subtypes demonstrate a prominent immune phenotype with marked CD8+ T lymphocyte infiltration, providing a further rationale for immunotherapy. NIDCR is interested in supporting research that aims to treat HNSCC through stimulation of the immune response focusing on checkpoint inhibition, adoptive T cell transfer, and vaccine therapies, and in combination with other cancer treatment. Malignancy of the oral cavity, oropharynx, and salivary glands are organ sites of priority to NIDCR.

    NIEHS and NCI

    NIEHS is interested in applications that explore how environmental exposures might affect cancer immunotherapy outcomes. Recent contributions in the field of environmental immunology have established the negative impact of toxicants on both the immune system and the effectiveness of immune responses to some vaccines. Current pre-clinical cancer trials or human population studies could potentially utilize available retrospective or actively collected biospecimens (blood, urine, plasma, etc.) appropriate for measurement of environmental exposures of interest, particularly those toxins known to have established links with immune suppression (including heavy metals, endocrine disruptors, and pesticides) to explore variation in efficacy of cancer immunotherapies. In addition to biological measurements, monitoring for air pollution parameters or geographic information systems or other spatiotemporal information on individuals, such as zip code at a certain point of time, could also be used to assess environmental exposure information. Animal studies exploring the interaction of common environmental toxicants with cancer immunotherapies would also greatly inform subsequent human clinical trials.

    NINDS and NCI

    Brain Tumors: There are unique challenges to developing effective immunotherapies for brain tumors, given the lymphatic system within the brain, immunosuppressive cells within the tumor microenvironment, and inability of certain therapeutics (e.g., antibodies) to cross the blood-brain-barrier (BBB). While clinical testing of checkpoint inhibitors, chimeric antigen receptor (CAR) T cells, and dendritic cell vaccines are currently underway, there are still pressing basic science questions to address. For example, do the checkpoint inhibitors need to cross the BBB to be efficacious in the central nervous system (CNS) or is it sufficient to activate T cells in the periphery that then migrate passively into the brain? An additional critical concern is whether or not effective immunotherapies can be developed to attack or prevent the spread of metastatic tumors in the brain. Research on primary brain tumor is considered mission relevant to NINDS while that focused on metastatic disease falls under the purview of NCI. Applications with either focus or both are encouraged.

    Specific Research Objectives

    The ultimate goal is to evaluate new or improved immunotherapy and combination interventional approaches identified through basic investigation of the mechanisms that contribute to immunosuppressed tumor microenvironments or resistance to immunotherapeutic regimens targeting unfavorable innate and/or adaptive immune functions. Studies should lead to the discovery of vulnerabilities that could be exploited to improve design of immunotherapies, including cancer vaccines, checkpoint inhibitors, cellular therapies, viral therapies, bispecific antibodies, and their combinations with other targeted interventions and/or radiation therapy for durable anti-tumor responses. Basic and pre-clinical studies utilizing clinically-relevant models and clinical specimens to enable rapid, efficient translation of these discoveries into future early-phase clinical evaluations are requested, although clinical trials are not supported through this FOA. The proposed pre-clinical studies may include analysis of human specimens that are delinked from patient identity but well-annotated with clinical information, and correlation of pre-clinical study results with available clinical information.

    Potential Areas of investigation include but are not limited to
    • Identification of factors contributing to tumor escape from immune surveillance, such as the altered expression of checkpoint proteins and immune-modulating proteins in tumors and other cells within tumor microenvironment, and the recruitment and activity of immunosuppressive cells in the tumor microenvironment
    • Identification and functional characterization of novel immune checkpoint proteins and changes in their expression following treatment with established checkpoint inhibitors or other immune-modulating approaches
    • Efficient priming of cytotoxic T cells, and enhancing expression of human leukocyte antigens, antigen presentation and dendritic cell (DC) function within the tumor microenvironment, as well as enhancing the trafficking of DCs between neighboring lymph nodes and the tumor site(s).
    • Studies focusing on pathways contributing to T cell exhaustion and experimental approaches to sustain T cell cytotoxic activity in vivo
    • Identification of tumor-specific T cell receptors and cognate tumor neoantigens
    • Discovery and evaluation of new or improved anti-cancer immunotherapies and/or combinations with immune-stimulating chemotherapies, radiation therapies, or other approaches for synergistic and durable anti-tumor responses
    • Optimization of safe and effective sequences of combination therapies involving immunotherapies
    • Investigation of intrinsic and extrinsic pathways leading to acquired resistance developed after treatment with immune-modulating regimens
    • Studies on identification of adjuvant therapies that target the gut microbiome to enhance anti-tumor efficacy or reduce toxicity of immunotherapies
    • Identification of tumor subtypes or locations within the tumor (e.g., necrotic core versus invasive edge) exhibiting enhanced or reduced susceptibilities to immunotherapies, and establishment of the mechanisms associated with these differential responses
    • Identification of immunotherapy approaches that will work in both the periphery, as well as the CNS, in an attempt to circumvent driving cancers into the brain after “curing” them in the periphery
    • Identification of immunotherapies that selectively target metastatic lesions that may exhibit distinct immune profiles or immunosuppressive microenvironments not present in the primary tumor
    • Avoiding or reducing off-target (or on-target, off-tumor) irAEs that limit the effectiveness of diverse immunotherapy approaches.
    Non-responsive Studies
    • Projects that focus on pediatric cancers; and
    • Specimen collection and banking that are not associated with experimental hypothesis.
    Eligibility and Scope of Work

    Applicants for cooperative agreement support should have the capacity to generate pre-clinical data based on preliminary findings in areas related to adult immunotherapy and tumor immune microenvironments. Hypothesis-driven applications should be focused on the study of basic mechanisms that render cancers susceptible or unresponsive to immune checkpoint inhibition, cancer vaccines, engineered T cell therapies, genetically-modified viral therapies, or other novel immune-modulating therapeutic approaches.

    Transdisciplinary approaches involving cell and molecular biologists, immunologists, pathologists, oncologists, surgeons, bioengineers, molecular imaging and radiation biologists, systems biologists, as well as bioinformaticians are encouraged.

    Every component citing and/or proposing preclinical research should ensure it meets the scientific rigor guidelines published by NIH (see https://grants.nih.gov/reproducibility/index.htm). Characteristics of any preliminary research results provided in support of a proposed project, whether conducted by the applicant or others, should be described in the application so that peer review may evaluate the strength of the supporting evidence. If preclinical data (e.g., animal studies) do not meet the rigor guidelines, the applicant should discuss the limitations of those data.

    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 required 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.

    Pre-Application Webinar

    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.

    Section II. Award Information
    Funding Instrument

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

    Application Types Allowed

    New
    Resubmission

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

    Clinical Trial?

    Not Allowed: Only accepting applications that do not propose clinical trials

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

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

    NCI intends to commit $7,000,000 in total costs in FY2019 to fund 8-9 awards.

    Award Budget

    Each application budget is limited to $500,000 in direct costs per year.

    Award Project Period

    The total project period request may not exceed 5 years. 

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

    Section III. Eligibility Information
    1. Eligible Applicants
    Eligible Organizations

    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
    • U.S. Territory or Possession

    Other

    Foreign Institutions

    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.

    Required Registrations

    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.

    Eligible Individuals (Program Director/Principal Investigator)

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

    2. Cost Sharing

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

    3. Additional Information on Eligibility
    Number of Applications

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

    The NIH will not accept duplicate or highly overlapping applications under review at the same time.  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).
    Section IV. Application and Submission Information
    1. Requesting an Application Package

    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.

    2. Content and Form of Application Submission

    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.

    Letter of Intent

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

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

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

    The letter of intent should be sent to:

    Nancy Boudreau, Ph.D.
    National Cancer Institute (NCI)
    Telephone: 240-276-6702
    Email: nancy.boudreau@nih.gov

    Page Limitations

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

    Instructions for Application Submission

    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.

    SF424(R&R) Cover

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

    SF424(R&R) Project/Performance Site Locations

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

    SF424(R&R) Other Project Information

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

    SF424(R&R) Senior/Key Person Profile

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

    R&R or Modular Budget

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

    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.

    R&R Subaward Budget

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

    PHS 398 Cover Page Supplement

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

    PHS 398 Research Plan

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

    Specific Aims: In addition to the specific aims and approach(es), applicants should include the relevance of the research to the objectives of this FOA.

    Research Strategy: The Research Strategy section should describe the following:

    • Expected impact of treating the cancer of focus if a positive outcome is achieved;
    • Significance of the proposed project for future clinical treatment of the cancer of focus;
    • Pre-clinical research approaches (along with potential pitfalls and alternative strategies) that address the overall goals of the FOA;
    • Clinical relevance of the pre-clinical study models and the proposed therapeutic strategies; and
    • Timeline for achieving the project goals.

    Health Disparities: If applicable to the type of research being proposed, address how minority health, 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 minority health 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.

    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 address a 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 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; (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" (https://biospecimens.cancer.gov/bestpractices/).

    Appendix:

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

    PHS Human Subjects and Clinical Trials Information

    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.

    PHS Assignment Request Form

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

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

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

    4. Submission Dates and Times

    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.

    5. Intergovernmental Review (E.O. 12372)

    This initiative is not subject to intergovernmental review.

    6. Funding Restrictions

    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.

    7. Other Submission Requirements and Information

    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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

    Post Submission Materials

    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.

    Section V. Application Review Information
    1. Criteria

    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.

    Overall Impact

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

    Scored Review Criteria

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

    Significance

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

    Specific to this FOA: How well does the project propose acceleration of translational research on immune resistance mechanisms leading to development of novel immune-based approaches to treat the cancer of focus in the application?  

    Investigator(s)

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

    Specific to this FOA: How well do Program Director (PD)/PI, multiple PD(s)/PI(s) and key personnel/consultants demonstrate strong scientific expertise in immuno-oncology and other scientific specialties required in the team to achieve the proposed goals? Are the investigators willing to collaborate with members of the IOTN Steering Committee?   

    Innovation

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

    Specific to this FOA: Does the applicant propose innovative plans for leveraging expertise and resources, integrating clinically-relevant information, and speeding translational research to maximize clinical benefits from cancer therapeutic approaches involving immunotherapies?   

    Approach

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

    Specific to this FOA: Is the clinical relevance of the pre-clinical study models and/or the proposed therapeutic strategies adequately addressed? How well do the proposed studies have potential to reduce cancer burden in the diverse population of the United States, including minority and underserved population? Are proposed studies appropriately powered, controlled, randomized, and blinded? Which project resources could be potentially shared among IOTN investigators and the broader scientific community? Does the application contain acceptable plans for addressing the NCI Cancer Moonshot? Public Access and Data Sharing Policy? 

    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?  

    Environment

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

    Additional Review Criteria

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

    Protections for Human Subjects

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

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

    Inclusion of Women, Minorities, and Individuals Across the Lifespan 

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

    Vertebrate Animals

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

    Biohazards

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

    Resubmissions

    For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

    Renewals

    Not applicable

    Revisions

    Not applicable

    Additional Review Considerations

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

    Applications from Foreign Organizations

    Not applicable

    Select Agent Research

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

    Resource Sharing Plans

    Reviewers will comment on whether the 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).

    Authentication of Key Biological and/or Chemical Resources:

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

    Budget and Period of Support

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

    2. Review and Selection Process

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

    As part of the scientific peer review, all applications:

    • 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.
    3. Anticipated Announcement and Award Dates

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

    Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

    Section VI. Award Administration Information
    1. Award Notices

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

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

    2. Administrative and National Policy Requirements

    All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, 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.

    NCI Responsibilities under Terms and Conditions of Cooperative Agreement:

    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.

    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 under this program;
    • Setting project milestones in consultation with NIH staff, and reporting progress and objectives to NIH staff;
    • Coordinating efforts and cooperating with the other components of the IOTN and with NIH Institute/Center (IC) 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).
    • 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;
    • Serving as a voting member on the IOTN Steering Committee;
    • 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;
    • Participating in NCI-coordinated evaluation of the IOTN program. 

    In addition to standard annual Research Performance Progress Report (RPPR) submissions, Principal Investigators 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 DHHS, PHS, and NIH policies. IOTN PD(s)/PI(s) are also encouraged to organize and participate in collaborative activities and scientific or programmatic working groups.

    NIH staff will 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.

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

    • Serving as a voting member on the IOTN Steering Committee;
    • Coordinating and facilitating interactions among investigators across the IOTN;
    • Working closely with investigators on research projects to coordinate and facilitate interactions/collaborations between 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 NIH 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;
    • Monitoring progress and direction of awardees and working groups as needed; and
    • Organizing and conducting regular meetings, as needed, to share progress between the awardees of the IOTN Consortium either by teleconference, videoconference, or face-to-face interaction.

    Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

    Areas of Joint Responsibility include:

    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 UG3/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 and procedures, guidelines and agreements;
    • 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. The 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.

    3. Reporting

    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.

    Section VII. Agency Contacts

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

    Application Submission Contacts

    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

    Scientific/Research Contact(s)

    Nancy Boudreau, PhD
    National Cancer Institute (NCI)
    Telephone: 240-276-6702
    E-mail: nancy.boudreau@nih.gov

    Minkyung (Min) Song, PhD
    National Cancer Institute (NCI)
    Telephone: 240-276-6139
    E-mail: songm@mail.nih.gov

    Gary J. Murray, PhD
    National Institute on Alcohol Abuse and Alcoholism (NIAAA)
    Telephone: 301-443-9940
    E-mail: gary.murray@nih.gov

    Katarzyna (Kasia) Bourcier, PhD
    National Institute of Allergy and Infectious Disease (NIAID)
    Telephone: 240-627-3482
    Email: bourcierkd@mail.nih.gov

    Chiayeng Wang, PhD
    National Institute of Dental and Craniofacial Research (NIDCR)
    Telephone: 301-827-4647
    E-mail: chiayeng.wang@nih.gov

    Kimberly A. McAllister, PhD
    National Institute of Environmental Health Sciences (NIEHS)
    Telephone: 919-541-4528
    E-mail: mcallis2@niehs.nih.gov

    Jane W. Fountain, PhD
    National Institute of Neurological Disorders and Stroke (NINDS)
    Telephone: 301-496-1431
    E-mail: fountai@ninds.nih.gov

    Peer Review Contact(s)

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

    Financial/Grants Management Contact(s)

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

    Judy Fox
    National Institute on Alcohol Abuse and Alcoholism (NIAAA)
    Telephone: 301-443-4707
    Email: jfox@mail.nih.gov

    Tina Carlisle
    National Institute of Allergy and Infectious Diseases (NIAID)
    Telephone: 240-669-2947
    Email: tc48k@nih.gov

    Diana Rutberg, MBA
    National Institute of Dental and Craniofacial Research (NIDCR)
    Telephone: 301-594-4798
    E-mail: rutbergd@mail.nih.gov

    Ashley Singh
    National Institute of Environmental Health Sciences (NIEHS)
    Telephone: 919-316-4593
    Email: ashley.singh@nih.gov

    Tijuanna Decoster, PhD
    National Institute of Neurological Disorders and Stroke (NINDS)
    Telephone: 301-496-9223
    E-mail: decostert@ninds.nih.gov

    Section VIII. Other Information

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

    Authority and Regulations

    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.

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