It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

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

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

Currently, the IOTN is composed of:

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

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

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

The purpose for i3 Centers to be supported by this FOA is to employ immuno-engineering principles to design more durable, accessible, and less toxic immunoprevention and immunotherapy strategies.

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 translation 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.

The goal of the IOTN consortium is to generate a comprehensive understanding of tumor-specific attributes that can be targeted with therapeutic and preventive interventions. This FOA solicits applications that incorporate innovative engineering solutions to accelerate the preclinical development of immunotherapeutic and immunopreventive interventions that are more effective, safer, and that could benefit a wider patient population - including pediatric, elderly, immunodeficient, underserved, and rare cancer patient populations.

Immuno-engineering to Improve Immunotherapy (i3) Center applicants should have the following capabilities:

• Ability to address the goals of this initiative, to employ immuno-engineering principles to design more durable, accessible, and less toxic immunoprevention and immunotherapy strategies.
• A broader goal that applicants are expected to consider is regenerating compromised immune systems of cancer patients that may have additional immune deficits due to existing co-morbidities or associated with normal aging.
• Multidisciplinary teams (i.e., bioengineers, chemists, immunologists, computational and cancer biologists) capable of incorporating next-generation genetic engineering, engineered biomaterials, nanotechnology, computational and mathematical modeling, or systems biology approaches in the design, implementation and evaluation of next generation immunotherapies.
• Research programs focused on complementary and synergistic innovative immuno-engineering projects that will accelerate translation of promising immunotherapy and immunopreventive approaches toward clinical applications.
• Multi-institutional collaborations that are encouraged to achieve the breadth of expertise required for a comprehensive research program capable of transforming how immune cells are manipulated to traffic to tumors, overcome immunosuppressive barriers, target tumor cells for killing, and generate long-lasting anti-cancer immunological memory.

Center Organization

The proposed i3 Centers must have the following structure:

• Administrative Core to manage and coordinate all i3 Center Research Project activities and serve as the liaison between the i3 Center and the IOTN Data Management and Resource-sharing Center (U24) and other Cancer Moonshot consortiums, including the Pediatric Immunotherapy Discovery and Development Network (PI-DDN). In addition, the administrative core will coordinate collaborative research activities between the i3 Center Research Project PD(s)/PI(s) and IOTN (or other) investigators.
• Research Projects should be comprised of well-developed and multifaceted approaches to advancing immunotherapy. Two to three Research Projects must be proposed for any one i3 Center. The proposed Research Projects of any one i3 Center must have a central organizing theme in which the tools or knowledge developed in one Project would inform the other Project(s), lending synergy to the proposed activities of the i3 Center. The i3 Centers will also be expected to support other cancer moonshot consortium investigators by providing novel immunoengineering solutions to address unmet needs in cancer immunoprevention or immunotherapy. Thus, an i3 Center’s proposed research areas must be broadly applicable to multiple cancer types, organ sites, and/or immunotherapies.

IMPORTANT NOTE: In planning the scientific scope of the i3 Centers to be proposed, applicants should align their proposed i3 Centers with one (and only one) Statement of Interest listed below. Applications that fail to focus on one specific Statement of Interest from the list below may be deemed non-responsive. Applicants wishing to address more than one Statement of Interest may do so by submitting separate applications.

National Cancer Institute (NCI) Statement of Interest (for applications aiming at assignment and funding solely by the NCI):

• The NCI is interested in supporting studies incorporating next-generation genetic engineering, engineered biomaterials, nanotechnology, computational and mathematical modeling, or systems biology approaches in the design, implementation and evaluation of next generation immunotherapies focused on overcoming immunosuppressive barriers, targeting tumor cells for killing, and generating long-lasting anti-cancer immunological memory. Potential areas of investigation include but are not limited to:
• Engineering improved bi- or multi-specific proteins and scaffolds for safe and effective engagement of immune cells with tumor cells;
• Developing next-generation gene-editing or modification of immune and non-immune cells to improve persistence in vivo, control and manipulate the immune system to reduce off-target toxicity, and enhance anti-tumor effectiveness of adoptive cell therapy;
• Developing artificial immune cells and/or functionalized lymphoid structures (scaffolds) using biomimetic strategies to augment or restore immune function;
• Developing biomaterials to control how, where, and when immune cells are stimulated in vivo to qualitatively shape anti-tumor immune responses;
• Developing and evaluating universal anti-tumor immune effector cells for broad populations of cancer patients who would benefit from receiving cell therapies in a timely manner;
• Designing targeted delivery of vaccines and immunomodulatory agents; and
• Deploying systems immunology platforms to enable predictive modeling of tumor and immune cell interactions and effects of therapeutic interventions.

National Institute on Aging (NIA) and NCI Statement of Interest (for applications aiming at NIA assignment with co-funding with the NCI):

The NIA is interested in supporting studies that focus on understanding the mechanisms regulating the immune responses of older individuals including T cell senescence, impairment of innate immune function and host factors that limit effective responses to immune therapies. Examples of NIA’s interests include the following types of research:

• Regulation of inflammatory responses in aged hosts that impede effectiveness of anti-tumor responses;
• Identify mechanisms of T-cell immunosenescence to support the identification of new targets for novel immunotherapeutic approaches;
• Identification of strategies such as artificial antigen presenting cells (APCs) and improved adjuvants to regenerate compromised immune responses in aged hosts for enhanced immunotherapy; and
• Studies that address cancer immunotherapy in older patients that are focused on developing less toxic immunotherapy for use in older individuals with co-morbidities

National Institute of Biomedical Imaging and Bioengineering (NIBIB) and NCI Statement of Interest (for applications aiming at NIBIB assignment with co-funding by the NCI):

The NIBIB is interested in supporting immuno-engineering projects that are focused on the development of technologies and applications of engineering design principles to modulate, control, or track immune cells and their interactions with other immune cells, cancer cells, or the tumor microenvironment. Preference for NIBIB funding, will be given to the meritorious applications focused on the development of technologies that have broad biomedical applicability and pertain to multiple cancers or relevant conditions such as inflammation. Examples of such areas of interest include but are not limited to:

• Engineering biomaterial-based artificial antigen presenting cells that can modulate immune cells or immune cell effectors to enhance immune response or overcome immune-suppression;
• Developing synthetic genetic circuits to sense and respond to tumor microenvironment conditions for the precision, on-demand delivery of immunotherapies and controlling immune cells;
• Design and developing controlled release delivery systems for precision targeting of immunotherapies;
• Developing tools that enable elimination of immune suppression by engineering immunity in tumor microenvironment;
• Deploying microfluidic platforms for scalable processing of engineered immune cells; and
• Developing imaging modalities and molecular imaging probes to track engineered immune cells and guide, monitor, enhance, and assess targeted immunotherapies

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

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

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

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

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

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

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

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

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

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

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• U.S. Territory or Possession

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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

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

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

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:

Kevin Howcroft, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6229
Email: Howcrofk@mail.nih.gov

Component Types Available in ASSIST

Research Strategy/Program Plan Page Limits

Overall

12

Admin Core (use for Administrative Core)

6

Project (use for Research Projects)

12

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required, maximum of 1
• Research Projects: required, minimum of 2, maximum of 3

When preparing your application, use Component Type Overall .

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions. The following additional instructions apply:

Project Summary/Abstract: Succinctly describe the overall research theme of the i3 Center and how immuno-engineering approaches will be utilized in accomplishing the research plan.

Project Narrative: State how the outcomes of the i3 Center will further knowledge in cancer immunotherapy or immunoprevention and the potential impact on public health.

Facilities and Other Resources:

In addition to standard elements, provide documentation for the following aspects reflecting the unique capabilities and attributes of the proposed i3 Centers:

• Provide supporting documentation to characterize the scientific environment(s) at the participating institutions, e.g., a Summary table(s) documenting institutional commitments, and other main characteristics/salient attributes of those institutions that are relevant to the goals and capabilities of the proposed i3 Center.
• If applicable, also include documentation for any active (ongoing) or past collaborations involving members of the multi-institutional teams proposed for i3 Center.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: State the overall vision and goals for the i3 Center. The Specific Aims should be overarching, at a high level, and distinct from the aims of the individual projects.

Research Strategy: In this section, present a concise overall vision and plan for the proposed i3 Center. This section should describe the fundamental question(s) in immuno-engineering that will be addressed by the i3 Center and how they integrate to form an overall research theme. Items to be addressed include:

• Research Theme. Define the overall research theme of the i3 Center. Provide a brief background and rationale and outline the significance of research in the selected area.
• Research Center Organization. Provide a concise description of the structure of the i3 Center and explain the following aspects: (1) how the skills of individual team members will translate into the collective capability of the center to accomplish the stated goals for transdisciplinary research and other activities; (2) your vision of the integration of the components into a Research Center as an entity that would be greater than the sum of its parts in terms of ability to advance fundamental question(s) in immuno-engineering and, (3) how the elements of the i3 Center, including key personnel, will interact to realize this vision. Briefly, state the administrative structure of the Administrative Core and activities directed by the Administrative Core and outreach plans to establish required collaborations that will advance the i3 Center's program and immuno-engineering efforts.
• Research Center Scientific Integration. In a brief overview, outline the rationale for each Research Project and the expected gains in terms of new knowledge advancing the research theme of the i3 Center. Explain how the Center's Research Projects will integrate and synergize. State how the Research Projects integrate to contribute directly to advancing the overall research theme of the i3 Center. Applications should demonstrate that use of the U54 Center mechanism is essential to accomplishing goals that would not occur without the climate, facilities, and research resources that a Research Center can uniquely provide. Outline plans for intra-Center communication that will facilitate scientific integration.

Letters of Support: In addition to standard items, applicants must provide letters from the respective leadership official(s) in the institution(s) of the proposed center documenting specific institutional commitments to the proposed center.

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.
• The Data Sharing Plan should be provided only under the Overall component but it should cover all the activities of the Center.
• The plan should briefly describe the types of data, software, and models that are expected to be generated and shared, consistent with achieving the goals of the IOTN.
• Data, software, and models from this FOA are expected to be shared in an easily accessible format with the scientific community to increase the value of the significant public investment. Note that the NCI Program staff may negotiate modifications to these plans prior to funding. Specifically, applicants will be expected to abide by the data, software, and model sharing plan developed by the IOTN Data Management and Resource-sharing Center and NCI program staff upon availability (see Section VI: Terms and Conditions of Cooperative Agreement).
• 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 items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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. Additional guidance:

Applicants may request primary assignment to the IC that best aligns to the research area that the proposed U54 i3 Center is focused on, as defined by the Statement of Interests listed in Section I of this FOA. If NCI is not requested as primary IC, then NCI should be requested as the secondary assignment.

When preparing your application, use Component Type Admin Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Each applicant must set-aside approximately 8% (Direct Costs) of year 2-5 funds to establish collaboration(s) to advance immunoengineering principles in the design of more durable, accessible, and less toxic immunoprevention and immunotherapy strategies.

An individual designated as a contact PD/PI must commit a minimum of 1.8 person-months effort per year to the Center. Any non-contact PD/PI must commit at least 1.2 person-months effort per year. These commitment levels cannot be reduced during the project period.

Applicants must budget for travel and per diem expenses for Steering Committee meetings. In the first year, applicants should plan for each Core and Project PDs/PIs to attend a Planning Meeting and one Steering Committee Meeting. In the second and subsequent years, applicants should plan for all PDs/PIs to attend one Steering Committee meeting per year.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Succinctly describe the strategies and goals for managing the i3 Center activities.

Research Strategy: The Administrative Core is expected to have appropriate and effective administrative and organizational capabilities to support multidisciplinary research teams, foster synergy and integration within the i3 Center and coordinate participation with the IOTN.

Under "Approach," describe the administrative structure to support the proposed i3 Center, including but not limited to:

Management and Communication Plan. Describe the plans for management and integration of i3 Center activities and evaluation of progress across the Center. Describe the leadership and communication strategies to manage and track progress of the multiple projects and sites that make up the i3 Center. Include a description of the Center leadership structure and concisely describe oversight mechanisms that will be used by the Center PD(s)/PI(s).

Network Activities. Provide a brief description of strategies for connecting and integrating the i3 Center with the IOTN. Funded i3 Center PD(s)/PI(s) are expected to participate in Annual Investigators meetings to present results and to communicate with other IOTN investigators. The i3 Center PD/PI (contact PD/PI for applications with multiple PDs/PIs) is expected to participate in the Program’s Steering Committee. The i3 Centers are also encouraged to organize and participate in other IOTN meetings and workshops, organize collaborative activities, and participate in scientific and programmatic working groups.

Outreach Plan. Provide a plan that describes how outreach will be conducted to the IOTN members to establish collaborations using the immuno-engineering tools and approaches developed by the i3 Center. Applicants do not have to identify prospective collaborators in the application but should present an outreach plan that will be used to identify and establish collaborations.

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. Resource Sharing Plans should only be provided in the Overall component of the application.

Appendix:

Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Administrative Core)

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

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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

When preparing your application in ASSIST, use Component Type Project.

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

SF424 (R&R) Cover (Research Projects)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Projects)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Projects)

• Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.
• Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.
• Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Research Projects)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Projects)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Research Projects)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Projects)

Specific Aims: This section should include the specific aims of the Research Project and key milestones.

Research Strategy: Describe the research strategy using the standard sub-sections of Research Strategy (Significance, Innovation, and Approach) defined in the SF424 Application Guide with additional guidance as defined below.

Clearly describe the immuno-engineering technologies and approaches addressed by the Project. Explain how the proposed approaches are expected to improve over existing immunotherapeutic or immunopreventive modalities. Highlight clearly any benefits/improvements that may have substantial transformative potential.

Milestones: At the end of Approach, use a separate heading "Milestones" to address the following aspects:

• A timeline (Gantt chart) including milestones is required. Milestones are intermediate steps towards the completion of concrete goals, that create go/no-go decision points in the project and must include clear and quantitative criteria for success.
• Yearly quantitative milestones are required in order to provide clear indicators of a project's continued success or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years.

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

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. Resource Sharing Plans should only be provided in the Overall component of the application.

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Research Projects)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads 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.

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 (SAM). 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.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this FOA, note the following:

Reviewers will provide an overall impact score for the entire i3 Center application. In addition, assigned reviewers will provide individual "criterion scores" for the Overall criteria but not for the other components.

All other components of the Center (i.e., Administrative Core and Research Projects) will be evaluated but each will receive only one overall adjectival (not numerical) rating. The merit assessment of all individual components will be reflected in the overall impact score.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the proposed i3 Center 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 i3 Center proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a proposed i3 Center that by its nature is not innovative may be essential to advance a field.

Does the proposed i3 Center 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 proposed i3 Center 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: What is the likelihood that the i3 Center, as proposed, will succeed in the design of immunotherapy and immunoprevention strategies that are more durable, widely accessible, and less toxic?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the proposed i3 Center? 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 strong is the applicants' scientific expertise in immuno-engineering and other complementary scientific specialties required for the team to achieve the proposed goals?

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: What is the likelihood that the immuno-engineering approaches will succeed in the design of immunotherapy and immunoprevention strategies that are more durable, widely accessible, and less toxic?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the proposed i3 Center? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the proposed i3 Center involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific for this FOA: Are the proposed immunoengineering Projects complementary and synergistic? Do the Research Projects integrate to contribute directly to advancing the overall research theme of the proposed i3 Center? Does the application contain acceptable plans for addressing the NCI Cancer Moonshot? Public Access and Data Sharing Policy?

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

Specific for this FOA: How well will the scientific environment at the participating institution(s) stimulate trans-disciplinary research collaborations? How well will multi-institutional teams, if applicable, take advantage of the distinctive strengths available through multi-institutional collaborations? How sufficient is the evidence of institutional support for the proposed i3 Center at the participating institution(s)?

As applicable for the i3 Center proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

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

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

When the proposed i3 Centers involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

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

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

Not applicable

Not applicable

Not applicable

As applicable for the i3 Center proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Not applicable

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

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

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

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

Reviewers will consider each of the review criteria outlined below to assess the scientific merit of the Research Projects. Reviewers will provide only one overall adjectival impact rating for each project (criterion scoring is not used for this component). The evaluation of each Research Project will be factored into the overall impact score.

Significance

Does the Research 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 Research 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?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Research 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? How well do applicants demonstrate strong scientific expertise in immuno-engineering and other scientific specialties required for the team to achieve the proposed goals of the Research Project?

Innovation

What is the likelihood that the proposed immuno-engineering approaches will provide a substantial improvement over current cancer immunotherapy or immunoprevention modalities?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Research 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? Are the approaches and goals of the Research Project integrated and complementary with the other i3 Center Research Project(s) in this application?

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?

Reviewers will provide one adjectival rating for the Administrative Core; individual criterion scores are not used for this component. The evaluation of each Administrative Core will be factored into the overall impact score. Reviewers will consider the following aspects while determining scientific and technical merit of this component:

• How well will the Core function to integrate the Research Projects?
• How well thought out are the plans and strategies to establish collaborative projects?
• Is sufficient attention devoted to outreach activities of the Core and plans for interactions/collaborations with other IOTN awardees and/or other immunotherapy investigators in years 2-5?

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

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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

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

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

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

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

• Defining objectives and approaches, and to ensure scientific rigor in the planning, conducting, analyzing, and publishing of results, interpretations, and conclusions of studies conducted under this program;
• Setting project milestones in consultation with NIH staff, and reporting progress and objectives to NIH staff;
• Serving as a voting member on the IOTN Steering Committee;
• 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;
• 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;
• Implementing Consortium-defined Common Data Elements (CDEs).
• Adhering to and complying with the decisions and recommendations of the IOTN Steering Committee to the extent consistent with applicable grant regulations.
• 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. The Communication Plan will clearly spell out interactive requirements that all IOTN Consortium PD(s)/PI(s) are expected to follow:
• Participating in regular conference calls and contributing to various sub-committees and working groups;
• Participating and presenting findings at IOTN annual investigator meetings;
• 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.
• 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 (https://cbiit.cancer.gov/ncip/cancer-data-commons).

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.

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

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

• 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 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;
• Monitoring institutional commitments and resources to the awardees;
• Suggesting reprogramming efforts, including options to modify projects/programs when certain objectives of this FOA are not met;
• Facilitating the development of 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.

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

Additional U54 Specific Responsibility of substantially involved NIH staff members include:

Meeting annually with other Moonshot coordinating centers to learn about the overarching capabilities of other coordinating centers; and coordinating, to the extent permitted, the standardization, harmonization and sharing of data and research resources, tools/platforms, including access to newly established biorepositories.

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

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel will be convened. The panel will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, 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 instructions, 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

Kevin Howcroft, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6702
Email: Howcrofk@mail.nih.gov

Minkyung Song, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6139
Email: songm@mail.nih.gov

Rebecca Fuldner, PhD
National Institute on Aging (NIA)
Telephone: 301-496-6402
Email: fuldnerr@nia.nih.gov

David Rampulla, Ph.D.
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Telephone: 301-451-4774
Email: David.rampulla@nih.gov

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

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

Linda Whipp
National Institute on Aging (NIA)
Telephone: 301-402-7731
Email: WhippL@nia.nih.gov

James Huff
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Telephone: 301-451-4786
Email: james.huff@nih.gov

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.