Immuno-Oncology Translational Network (IOTN): Cancer Immunotherapy Research Projects (U01)

Immuno-Oncology Translational Network (IOTN): Cancer Immunotherapy Research Projects (U01) is sponsored by National Cancer Institute (NCI). This opportunity supports mission-aligned projects and measurable outcomes.

Expired RFA-CA-17-045: Immuno-Oncology Translational Network (IOTN): Cancer Immunotherapy Research Projects (U01) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) of Participating Organizations National Cancer Institute ( NCI ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) 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) U01 Research Project Cooperative Agreements October 31, 2018 - This RFA has been reissued as RFA-CA-19-015 .

October 31, 2018 - This RFA has been reissued as RFA-CA-19-014 . October 12, 2017 - Notice of a Pre-Application Webinar for the Immuno-Oncology Translation Network (IOTN). See Notice NOT-CA-18-005 .

Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity RFA-CA-17-046 , U01 Research Project Cooperative Agreements RFA-CA-17-047 , U24 Resource-Related Research Projects Cooperative Agreements RFA-CA-17-048 , U24 Resource-Related Research Projects Cooperative Agreements Additional Information on Eligibility . Catalog of Federal Domestic Assistance (CFDA) Number(s) 93. 353, 93.

273, 93. 121, 93. 113, Funding Opportunity Purpose This Funding Opportunity Announcement (FOA) is associated 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 goal of the network is to foster collaborative team science approaches to accelerate the discover of 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.

The purpose of this FOA is to establish a Cancer Immunotherapy Consortium (CIC) composed of organ site-specific Cancer Immunotherapy Research Projects as a component of the Immuno-Oncology Translation Network (IOTN).

The CIC 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) resulting in durable anti-cancer responses.

Studies should be largely pre-clinical involving clinically-relevant models and endpoints. Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 30 days prior to the application due date January 16, 2018, 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) It is critical that applicants follow the Research (R) Instructions (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 I. Funding Opportunity Description Section II. Award Information Section III.

Eligibility Information Section IV. Application and Submission Section V. Application Review Information Section VI.

Award Administration Information Section VII. Agency Contacts Section VIII. Other Information Full Text of Announcement Section I.

Funding Opportunity Description This funding opportunity announcement (FOA) will establish 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 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.

of the Immuno-Oncology Translation Network companion FOAs will support the establishment of the IOTN with the following Immunotherapy Consortium (CIC): The CIC will be composed of organ Immunotherapy Research Projects ( to be supported by this FOA, RFA-CA-17-045 ) Immunoprevention Research Projects (to be supported by RFA-CA-17-046 ).

The CIC will form an integrated network of multi-disciplinary, collaborative teams with the overarching goals of accelerating the development of improved immunotherapeutic strategies capable of eliminating established cancers or preventing cancers before they occur.

Approximately, 10-12 U01s are expected to Management and Resource-Sharing Center (DMRC): The DMRC (one U24 to be supported under RFA-CA-17-047 ) will provide overall support, and facilitate collaboration among the adult IOTN-funded components. The DMRC will also promote scientific outreach with other Cancer Moonshot initiatives and the larger scientific community.

Immunotherapy Data Resource (CIDR): The CIDR (one U24 to be supported under RFA-CA-17-048 ) will support a data registry for collecting outcomes of patients receiving cellular immunotherapies, that could be utilized for observational studies or inform subsequent pre-clinical studies and clinical trials.

of the IOTN: The IOTN, including DMRC, CIDR, and the Cancer Immunotherapy and Immunoprevention Research Project components will be governed by the IOTN Steering Committee. ( see Section VI: Terms and Conditions of Cooperative Agreement .)

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

purpose of this specific FOA is to establish the Cancer Immunotherapy Research 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 Scientific Scope of the CIC 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 CIC 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 CIC investigators by 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 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: 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 are also encouraged.

cancers are characterized by an extremely immunosuppressed microenvironment, and not surprisingly show limited responses ( 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. 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 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.

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.

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. Malignancy of the oral cavity, oropharynx, and salivary glands are organ sites of priority to NIDCR. 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.

Tumors : There are unique challenges with developing immunotherapies for brain tumors, given the immune-privileged environment of the brain and inability of certain therapeutics (i.e., antibodies) to cross the blood-brain-barrier (BBB). Early phase clinical testing of checkpoint inhibitors is currently underway but there are 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 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 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 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 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 Avoiding or reducing off-target (or on-target, off-tumor) immune-related adverse events (irAEs) that limit the effectiveness of diverse immunotherapy approaches.

Projects that focus on the immune microenvironment of Pancreatic Ductal Adenocarcinoma supported under the RFA-CA-17-015 Projects that focus on pediatric cancers.

Specimen collection and banking that are not associated with Initiation of new clinical trials of investigational treatment 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 are encouraged to reach out to the Scientific/Research Contact listed in Section VII below to ensure appropriate alignment of projects with available Pre-Application Teleconference A technical assistance teleconference will be held for potential applicants.

NIH staff will be available to answer questions related to this FOA. Time, date, and dial-in information for the call will be announced in VIII. Other Information for award authorities and regulations.

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 Application Types Allowed Glossary and the SF424 (R&R) Application Guide provide details on Funds Available and Anticipated Number of Awards NCI intends to commit $7 million in total costs in FY Each application budget is limited to $500,000 in direct The total project period request may not exceed 5 years.

Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education: o Hispanic-serving Institutions o Historically Black Colleges and Universities (HBCUs) o Tribally Controlled Colleges and Universities (TCCUs) o Alaska Native and Native Hawaiian Serving Institutions o Asian American Native American Pacific Islander Serving Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Nonprofits without 501(c)(3) IRS Status (Other than Institutions For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Institutions) are Non-domestic (non-U.S.) components of U.S. Organizations are not eligible Foreign components, as defined in the NIH Grants Policy Statement , are allowed.

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 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 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. 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.

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 must have an active DUNS number and SAM registration in order to complete the 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 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 This FOA does not require cost sharing as defined in the NIH Grants Policy Statement . 3.

Additional Information on Eligibility 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 A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission 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 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 (R&R) Application Guide , including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise.

Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant 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 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: National Cancer Institute (NCI) All page limitations described in the SF424 Application 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 All instructions in the SF424 (R&R) Application Guide SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide 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 PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Aims: In addition to the specific aims and approach(es), applicants should include the relevance of the research to the objectives of this The Research Strategy should describe the following: Expected impact of treating the cancer of focus if a positive 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.

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 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.

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 The data sharing plan will become a term and condition of award. Do not use the Appendix to circumvent page limits.

Follow all instructions for the Appendix as described in the SF424 (R&R) PHS Inclusion Enrollment Report When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 PHS Assignment Request Form All instructions in the SF424 (R&R) Application Guide 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