Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization.

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.

No late application will be accepted for this Funding Opportunity Announcement.

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from 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 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The overall goal of this funding opportunity announcement (FOA) is to advance new cell therapy strategies into clinical testing for the treatment of solid tumors in adult cancer patients (18 years or older). The successful applications to this FOA (and companion FOAs for the study of pediatric solid tumors and the establishment of a U24 Coordinating Center) will establish the Cancer Adoptive Cellular Therapy (Can-ACT) Network, dedicated to developing innovative cell therapy approaches for treatment of solid tumors. This Network of investigators will, through novel and collaborative approaches to preclinical and translational studies, bring new cell therapy products into clinical trials.

Awards made under this FOA will initially support a two-year maximum, milestone-driven UG3 phase, with a possible transition to a clinical trial implementation phase (UH3) of up to three years duration. Progression to the UH3 phase is based on an administrative review and is dependent on meeting UG3 milestones, NCI programmatic priorities, and the availability of funds. Only UG3 grants that have met scientific milestones and feasibility requirements related to initiation of a clinical trial will be considered for transition to the UH3 phase.

The UG3/UH3 application must be submitted as a single application with the design of the exemplary UH3 clinical trial described in the application, following the instructions described in this FOA. The UG3 phase permits preclinical, translational, and IND-enabling studies. The UH3 phase must include initiation and conduct of an early phase, proof-of-concept, or first-in-human investigator-initiated, single-site, or multi-site clinical trial. NCI may assist UH3-funded multi-site clinical trials using resources from the Immune Cell Network Core (ICN Core) at the Frederick National Laboratory for Cancer Research (FNLCR).

Investigators have the opportunity and are encouraged to use the ICN Core for cell manufacturing in multi-center trials.

Background

Progress in cancer adoptive cell-based therapy (ACT) for hematologic malignancies, along with an enhanced understanding of the tumor immune microenvironment and advances in cellular and molecular technologies, has now permitted the expansion of ACT to solid cancers. ACT can be further divided into several subtypes, among them: 1) chimeric antigen receptor (CAR) T-cell therapy; 2) tumor-infiltrating lymphocyte (TIL) therapy; 3) engineered T cell receptor (TCR)-T cell therapy; and 4) natural killer (NK) cell and dendritic cell (DC) therapies. CAR T-cell therapies are the best studied and most widely known, as several have been approved by the Food and Drug Administration (FDA) for the treatment of patients with acute lymphoblastic leukemia, non-Hodgkin lymphoma, and multiple myeloma. However, improvements in adoptive cell therapeutic strategies are needed to effectively treat adult cancer patients with solid tumors.

The NCI has a long history of supporting the immuno-oncology research community in basic, translational, and clinical studies through grants and clinical trial networks. The NCI convened workshops in 2018 and 2020 to identify areas of need in cell-based immunotherapy for solid tumors. These meetings brought together extramural academic researchers, industry scientists, FDA representatives, and NCI staff, allowing NCI to gain insight on major challenges and future directions in the field (see published meeting summary).

Existing needs identified by the ACT community for further development of cell-based strategies for solid tumors include: improved manufacturing approaches, studies of immune cell fitness/persistence and trafficking, strategies to overcome the immunosuppressive tumor microenvironment, development of novel biomarkers and imaging methods, a core laboratory to measure critical quality attributes of manufactured cell products and perform quality control (QC) testing on cell therapy-related reagents, and support for small proof-of-concept clinical trials to rapidly gain knowledge of promising new treatment approaches.

In an effort to continue to support the ACT community, the NCI has established the Immune Cell Network Core Facility (ICN Core) at the Frederick National Laboratory for Cancer Research (FNLCR). The ICN Core has the capabilities for the production of GMP-grade cell products and vectors, and standardization of assays. The ICN Core will provide guidance for quality systems and regulatory affairs for all sites, when requested, and cell product manufacturing for multi-site clinical trials.

Organization of the Can-ACT Network

The Can-ACT Network is designed to accelerate the development and testing of adoptive cell

therapy for solid tumors in adult and pediatric patients. The UG3/UH3 milestone-driven NCI-collaborative grant mechanism will allow awardees to explore novel cell therapy approaches and to generate preclinical IND-enabling data during the initial UG3 phase, and then rapidly test these approaches in early phase, proof of concept, or first-in-human clinical trials in the UH3 phase. The UG3/UH3 awardees are expected to communicate scientific approaches and data within the network. While single-site trials are permitted, the intent of the network is to leverage the Frederick National Laboratory for Cancer Research (FNLCR) Cell Production and Immune Cell Network Core (ICN Core) facilities and services for small multi-site trials to achieve timely accrual goals. The U24 Coordinating Center will facilitate interaction and cooperation between UG3/UH3 awardees, the FNLCR Cell Production and ICN Core facilities, and NCI project scientists and program officers.

Three FOAs listed below along with the ICN Core at FNLCR will support the Can-ACT Network:

• Can-ACT for Adult Cancers (RFA-CA-22-028);
• Can-ACT for Pediatric Cancers (RFA-CA-22-029); and
• Can-ACT Coordinating Center (RFA-CA-22-030).

The NCI will work with the U24 Coordinating Center and Can-ACT network to determine how data from the cell therapy products used in the clinical trials supported under these FOAs as well as the clinical trial data will be developed, collected, stored, shared, and maintained.

The Can-ACT Network will be governed by the Can-ACT Steering Committee.

Resources provided by NCI: Immune Cell Network (ICN) Core

The FNLCR houses the ICN Core, which will be providing services for the Can-ACT Network. What follows is the general assistance to be provided by the ICN Core. Based on the applications received, awards made, and ongoing guidance from the Division of Cancer Treatment and Diagnosis (DCTD), minor changes may be made to best align with the needs of the Can-ACT Network.

The ICN Core will facilitate and support the following activities:

• Quality Oversight: The ICN Core will provide Good Clinical Practice (GCP) and Good Manufacturing Practice (GMP) compliance evaluations for the sites, as requested. The ICN core will perform virtual or on-site visits, as appropriate, for Good Clinical Laboratory Practices (GCLP) compliance.
• Product Attributes Evaluation: In consultation with the Can-ACT members and NCI, the ICN Core will develop and standardize characterization assays for cell therapy products to be used for clinical trials. The ICN Core may produce and distribute key assay reagents and Standard Operating Procedures to Can-ACT members. The ICN Core will provide quality assurance and regulatory guidance to Can-ACT members, as well as guidance and review of materials for IND submission to the FDA.
• Multi-site Trial Current Good Manufacturing Practice (cGMP) Production: The ICN Core will be available to Can-ACT member sites for the production, testing, release, and distribution of cGMP cell therapy products for multi-site Can-ACT clinical trials, including the coordination of autologous raw material and final product logistics between clinical and manufacturing sites. The ICN Core will develop innovative engineering and production processes, as needed.

Specific Research Objective and Requirements

The long-term objective of Can-ACT is to foster innovation and promote early-stage clinical testing of novel state-of-the-art cell-based immunotherapies for solid tumors in adults and pediatric patients and leverage NCI resources to support the cell therapy community. A U24 Coordinating Center, in conjunction with NCI staff will facilitate collaborations within the network.

Through this FOA, NCI solicits applications from muti-disciplinary teams for discrete research objectives and clinical trials to establish the adult component of the Can-ACT Network. The teams of investigators will have relevant and complementary expertise and will collaborate to address the unique barriers preventing effective cell therapy in adult cancer patients with solid tumors. The overall goal of this FOA is translation of the tested cell therapy concepts to early phase clinical trials in adult cancer patients. Multiple Project Director/Principal Investigator (PD/PI) and multi-institutional collaborations are encouraged to apply to strengthen novel scientific approaches to adoptive cell therapy research. Awards made under this FOA will initially support a two-year maximum, milestone-driven UG3 phase, with a possible transition to a clinical trial implementation phase (UH3) of up to three years. Progression to the UH3 phase is based on an administrative review and is dependent on success in meeting UG3 milestones, NCI program priorities, and availability of funds. Only UG3 grants that have met scientific milestones and feasibility requirements related to initiation of a clinical trial will be considered for transition to the UH3 phase.

UG3 phase

The UG3 part of the application must address at least 2 objectives that will advance a new cell therapy concept to clinical testing while also conducting research to advance the understanding and clinical use of cell therapies to treat adult cancer patients with solid tumors. Collaborative team members must consist of appropriate interdisciplinary expertise and capabilities across preclinical and/or translational science to achieve their scientific research objectives.

Examples of the major objectives include but are not limited to:

• Efforts to improve cell therapy genetic modifications and/or cell therapy manufacturing, such as new cell expansion methods, genetic engineering inc luding multigene engineering, alternatives to lentiviral or retroviral-based gene delivery, optimization of closed system manufacturing, new strategies for cell product screening, etc.
• Strategies to modulate the immunosuppressive tumor microenvironment to enhance cell therapy efficacy, for example through combinatorial radiation treatment.
• Development of biomarkers for cell product activity and host response to guide therapeutic use of cell therapies.
• Use and optimization of existing imaging agents and quantitative tools for monitoring of cell trafficking, tumor infiltration, and anti-tumor and immunosuppressive tumor microenvironment (TME) modulation effects, as well as to track survival, activation, expansion, exhaustion, and tumor-specific targeting of adoptively transferred cells.
• Development of new imaging agents and imaging approaches for direct longitudinal imaging of cell persistence and long-term anti-tumor immune response.
• Combination of imaging and biomarker approaches to accurately monitor patient disease and response to adoptive cell therapy, toxicity, and to detect the emergence of treatment resistance at the earliest time point.

The UG3 phase is projected to last 2 years and must include clearly outlined milestones and go/no go criteria. Only grants that will complete all milestones outlined in the UG3 phase and will be ready to initiate a clinical trial will be considered for advancing to the UH3 phase.

UG3 phase to UH3 phase transition

An administrative review will be conducted by NCI program staff to decide whether a UG3 phase grant will be transitioned into the UH3 phase based on the following criteria:

• Successful achievement of defined milestones in the UG3 phase of the grant;
• Clear evidence that the Center can initiate a clinical trial in the first year of the UH3 phase;
• Availability of funds; and
• Programmatic priorities.

All tasks needed for launching a clinical trial in the first year of the UH3 phase must be completed. These may include the following:

• Approved IND for clinical trial proposal;
• IRB approval of the clinical trial protocol;
• Plan for patient recruitment to meet enrollment goals;
• Submission of the final clinical protocol and supporting documents to NIH for administrative review, and notification of approval by NIH;
• Clearly defined timeline, milestones, and budget for the clinical study;
• Confirmed availability of therapeutic agents for proposed trial, including manufacturing capacity for cell products; and
• Plan to ensure GCP adherence among multi-site Network trials (full clinical monitoring responsibility remains with the IND-holding Network member).

UH3 phase

The UH3 phase of the application must contain a clinical trial for a novel cell therapy treatment of a solid tumor generally occurring in adults (18 years or older). Note, a lower age limit may be considered if it can be justified based on tumor type. The application must contain a detailed outline of a sample proposed trial, including eligibility criteria, enrollment plan, treatment schema, safety monitoring plan, regulatory plans and reporting, and a statistical analysis plan.

Single-site or multi-site clinical trials are eligible. Investigators submitting applications for multi-center clinical trial are encouraged to request and obtain support from the NCI ICN Core at FNLCR. Single-site trials will not be eligible for cGMP cell manufacturing support from the ICN Core at FCLNR (although ICN-supported multi-center trials may initially begin as a single site prior to expanding to multiple sites).

Continued funding during the UH3 phase will be dependent upon meeting annual UH3 milestones, and it is expected that the study will be completed within the UH3 grant period. Clinical trials supported during the UH3 phase should be hypothesis-driven, milestone-defined, and have the potential for high impact within the research mission of the NCI. The clinical trial must meet all applicable NIH, Food and Drug Administration (FDA), and Office for Human Research Protections (OHRP) policy requirements.

Additional Information

Multi-site Studies: Applications that propose multi-site studies with multiple domestic sites are subject to the NIH Single IRB policy as indicated in NOT-OD-16-094 and the Revised Common Rule cooperative research provision 45 CFR 46.114.

Delayed onset studies will not be supported by this FOA.

Pre-Application Information Session: NIH staff will hold a teleconference for potential applicants to answer questions related to this and companion FOAs. Time, date, and dial-in information for the call will be announced at a later date in an NIH Guide Notice.

Consultation: Potential applicants to this FOA are strongly encouraged to consult with the Scientific/Research Contact(s). Early contact is highly encouraged as it may provide additional guidance on using NCI’s vector and cell manufacturing facilities that can be available through NCI Immune Cell Network Core.

Non-Responsive Applications

The following types of activities remain outside the scope of this FOA, and applications proposing them will be considered non-responsive to this FOA and will not be reviewed:

• Applications that focus on pediatric tumor indications, unless a justification can be made for studying this in adults;
• Applications that focus on hematologic malignancies;
• Basic research and studies of disease mechanisms;
• Animal model development (all in vivo models must be well established, reproducible, and available to the applicant);
• Applications lacking an outline of a proposed clinical study protocol included with the submission (UH3 phase);
• Applications lacking milestones and go/no go decisions for the UG3 and UH3 phases; and
• Applications proposing Phase II/III registration trials.

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

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

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Government

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not 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.

• 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.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; 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 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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support.

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications)

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace 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 instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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

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

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

The letter of intent should be sent to:

Kasia Bourcier, Ph.D.
Division of Cancer Treatment and Diagnosis
National Cancer Institute (NCI)
Telephone: 301-846-1101
Email: [email protected]

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

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

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

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

The clinical trial must be directed by PD(s)/PI(s) with experience in the conduct of clinical trials and expertise in the disease area. The application should also indicate the prior experience of other study team members in clinical trial design and implementation. The experience must be documented in the biosketch, including timely submission of primary publications from previous trials. The application must contain information about key personnel in the biosketch of the multidisciplinary team (clinical trialist, clinician, project manager, study coordinator(s), statistician, bioinformatician, etc.) to ensure that contributing institutions can facilitate the implementation of all aspects of the clinical trial, including recruitment of subjects, design/implementation of the trial protocol, and coordination of roles/responsibilities. The PI must dedicate at least 1.8 person months effort per year to the project for the life of the award. If the project has Multi-PIs, then each must dedicate at least 1.2 person months effort per year to the project for the life of the award.

R&R Budget

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

A complete detailed budget is required for both the UG3 phase and the UH3 phase. The applicant should estimate the costs for the UH3 phase based on the scope of work described in the application for the UH3 phase. Budget justifications must be included. The PI must dedicate at least 1.8 person months effort per year to the project for the life of the award. If the project has Multi-PIs, then each must dedicate at least 1.2 person months effort per year to the project for the life of the award.

If it is proposed that NCI will provide cGMP cell product manufacturing and shipment for multi-site clinical trials, costs for these activities are not to be included in the budget.

If parts of the costs of the study are to be borne by sources other than NIH, these contributions must be presented in detail in the budget justification. These outsourced costs do not constitute cost sharing as defined in the current NIH Grants Policy Statement and should not be presented as part of the requested budget.

Budget requests must include travel costs for the PD(s)/PI(s) to attend the initial in-person kick-off meeting, and for the PD(s)/PI(s) and other members of the project team (up to four people in total) to attend the annual Can-ACT Investigators' meetings. Meetings will be held in the Washington DC metropolitan area. PDs/PIs are encouraged to include early career scientists in Can-ACT activities and also, should include a budget for at least one graduate student or postdoctoral fellow to travel to the Annual Investigators Meeting.

The release of the funds will be contingent on accomplishing milestones and this requirement will be specified in the Notice of Grant Award.

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

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

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

Specific Aims: Include distinct aims for UG3 Phase and UH3 Phase clinical trial. Provide a rationale and description of how application advances the cell therapy field and which need of the field is addressed. Describe how the current concepts, methods, and/or technologies in adoptive cell therapies will be changed if the Specific Aims are achieved.

Research Strategy: Applicants should describe both the UG3 phase and UH3 phase using the standard sub-sections of Research Strategy (Significance, Innovation, and Approach) defined in more detail in the SF424 Application Guide with additional guidance as defined below.

Significance: Discuss how the proposed concept addresses gaps in cell therapies for solid tumors. Explain the significance of the problem or critical barrier to progress in adaptive cell therapy that the application is trying to address, and why the proposed approach or technology is needed to realize a solution.

Specific to this FOA:
The scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention should be supported by preliminary data, clinical and/or preclinical studies, information in the literature, or knowledge of biological mechanisms. The results from the UG3 phase should well inform the clinical trial proposed in the UH3 phase.
For trials focusing on clinical or public health endpoints, describe how this clinical trial will contribute to testing the safety, efficacy, or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors, or health care policy. For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, describe how well this trial will advance scientific understanding, and how well the clinical trial results are expected to further the immune cell therapy field for the treatment of solid tumors.

Innovation: Explain how the proposed strategy advances the cell therapy field’s concepts. Evaluate existing knowledge and approaches that have been or are being applied in this area of research and specifically describe how the proposed approach will advance the field. Identify clearly any innovative biological concepts that are proposed to be explored as a potential basis for novel cell therapy strategies for solid tumors.

Approach: This section should include a description of supporting data and the experimental approach. Address benefits of the multi-team approach. Present the uniqueness of the team, the key milestones, go/no go decisions, and the expected outcomes of the proposal.

Specific to this FOA:
The application should adequately address Good Clinical Practices (GCP), Good Laboratory Practices (GLP), and Good Manufacturing Practices (GMP) compliance.

UG3 Phase - UG3 part of the application must address at least two hypotheses-driven objectives that will advance a new cell therapy concept to clinical testing. The proposals should have a clear milestone-driven plan to achieve these goals.

UH3 Phase - Clinical trial proposal

Recognizing that a final clinical trial approach and design is predicated on the observations and discoveries during the UG3 phase, the applicant should provide an example trial and how the UG3 phase will impact their proposal. The UH3 proposed sample clinical trial example should provide the following:

• Scientific justification to the approach proposed including the hypothesis being tested;
• Primary and secondary objectives;
• Treatment plan including the schedule and types of evaluations being performed, supportive care, and treatment modifications when appropriate;
• The rationale for the trial approach and design;
• The trial endpoints and the method(s) of their assessment (e.g., safety, clinical outcomes, and changes in correlative biological markers);
• The plan for correlative/mechanistic studies with justification for any longitudinal sample collections and plan for collection, preparation, and storage of collected samples;
• Explain how the proposed clinical trial will ensure the appropriate enrollment of patients reflective of the focus areas proposed for the clinical trials;
• Describe considerations around equity and diversity of participation including racial/ethnic minorities and women.
• Feasibility of conducting the trial including accrual plans, expected ineligibility rate, and enrollment timeline;
• Detail on the specific investigational agent(s), handling, preclinical data if available (or how this will be incorporated), potential toxicities, and administration of the agent(s);
• A statistical design (primary/secondary endpoints) including stratification strategies as appropriate and sample size justification;
• An analysis plan including plans for formal interim analysis as needed;
• A description of the safety and data monitoring plan to ensure adherence to the protocol including the strategy for reporting data and outcomes to the Safety and Data Monitoring Board (SDMB), IRB of record, institutional officials, NIH, and FDA;
• Description of the documentation process for consent, agent administration, adverse events, and clinical outcomes;
• Description of the methods and platform proposed to assure the reporting fidelity of study monitoring, data recording, query resolution, exception, and deviation management, and locking final dataset for analysis (e.g., paper or electronic data collection systems, and CFR 21 part 11 compliance);
• Description of planned Data software capabilities (e.g., data sharing and compatibility for uploading to established NIH Data commons such as dbGAP);
• Description of standards for data types, formats, minimal requirements, compatibility for storage and analysis, integration, and sharing of clinical and correlative data among the network members in accordance with NIH Policy for Data Management and Sharing (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-21-013.html); and
• Description of how the ICN Core and Cell/Vector Production Facility would be used for multi-site trials that plan to use the facility.

This section should also provide a description of the following facilities:

• Local cell production facilities as applicable, excluding the ICN Core, if proposed;
• Clinical outpatient and inpatient facilities including ICUs and types of clinical consultation services available to assure the safe conduct of the trial;
• Pharmacy and Blood Bank/Autologous Cell Facilities; and
• If applicable, a description of monitoring of participating facilities such as labs or pharmacies for adequate handling and storage of investigational products and study specimens.

Specific to this FOA:
The collaborative objectives in the UG3 phase led by institutions should significantly contribute to the advancement of the cell therapy field. Describe how appropriate the administrative, data coordinating, enrollment, and laboratory/testing centers are for the trial proposed. The application should adequately address the capability and ability to conduct the trial at the proposed site(s) or centers, and describe plans to add or drop enrollment centers, as needed. If multi-sites/centers, provide evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure.

Milestones and Timeline

A timeline including milestones is required for all phases of the application (UG3/UH3). Milestones are goals that create go/no go decision points in the project and must include clear and quantitative criteria for success. 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. The application must include clearly-specified, well-defined milestones, quantitative go/no go decision points, and timelines for assessing progress in both the UG3 and UH3 stages, including specific milestones and timeline for UG3 and UH3 phases. Milestones and the timeline for each stage must be provided in a separate heading at the end of the Approach section for each UG3 and UH3 component and include the following:

• Detailed quantitative criteria by which milestone achievement will be assessed;
• Detailed timeline for the anticipated attainment of each milestone and the overall goal;
• Impediments that could require an addendum to the research plan, milestones, or timeline with a discussion of alternative approaches; and
• Strong understanding of the regulatory requirements of the project (e.g., FDA pre-submission meeting(s), submission of an IDE, etc.).

Health Disparities: If applicable to the type of research projects being proposed, the Research Strategy must address how minority health, health disparity populations, or data will be integrated into the proposed studies.

Letters of Support: Letters of support from clinicians or clinical department chairs whose support is necessary to the successful conduct of the trial must be provided. This includes letters from the Cell Manufacturing facilities, if applicable.

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.

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• A Resource Sharing Plan for data (including genomic data), unique materials (including biological materials such as patient-derived cells, organoids and tissues), tools, model organisms, reagents, and therapeutics, along with IP and knowhow management should be provided by each Research Project application and should cover all the activities proposed for the UG3/UH3 Research Project and within the context of the Can-ACT, where applicable.
• Resource Sharing Plan should briefly describe the types of data and computational resources and unique biological resources that are expected to be generated and shared, consistent with achieving the goals of the Can-ACT.
• Resource Sharing Plans are expected to describe plans for anonymization, annotation, multimodal data integration; harmonization; transfer learning; development of robust statistical-, Artificial Intelligence-and/or Machine Learning-ready datasets to facilitate formats that are accessible to increase the value of these data and unique resources for sharing with the scientific community.
• Formats, analytical algorithms, computational modeling and visualizations, and other bioinformatics tools resulting from this FOA are expected to be compatible with the NIH-approved bioinformatics platforms, such as those designed and implemented by the NCI Center for Bioinformatics platforms (https://cbiit.cancer.gov/data-sharing).
• To facilitate the establishment of a Can-ACT database, Network members will be expected to adhere to data collection and harmonization policies set forth by the Can-ACT Coordinating Center in collaboration with NCI and the Network members.

Note that NCI Program staff may negotiate modifications to these plans prior to funding. Specifically, applicants will be expected to abide by the policies and procedures for unique resources and data, software, and computational model sharing within the context of the NCI Cancer Data Ecosystem including infrastructure and resources for access of multi-modal data, elastic computation, and analysis through the Cancer Research Data Commons developed upon availability (see Section VI: Terms and Conditions of Cooperative Agreement).

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

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

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

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

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit 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) must include their eRA Commons ID in the Credential fieldof the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the NCI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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

Section V. Application Review Information

1. Criteria

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.

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.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Overall Impact

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

Scored Review Criteria

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

Significance

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

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Specific to this FOA:

How well are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? How well will results from the UG3 phase inform the clinical trial proposed in the UH3 phase? How well does the clinical trial address a gap in the immune cell therapy field for the treatment of solid tumors?

For trials focusing on clinical or public health endpoints, how well will this clinical trial contribute to testing the safety, efficacy, or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors, or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, how well will this trial advance scientific understanding? How well are the clinical trial results expected to further the immune cell therapy field for the treatment of solid tumors?

Investigator(s)

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

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Innovation

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

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Specific to this FOA:

How well does the proposed project represent an innovative concept, technological solution, and/or approach for improving adaptive cell therapy for adult patients with solid tumors? How innovative is the design/research plan, and how well will any innovative elements enhance its sensitivity, potential for information, or potential to advance scientific knowledge or clinical practice?

Approach

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Specific to this FOA:

How well is a collaborative project in phase UG3 taking advantage of a multi-center approach to spearhead a new translational application? To what extent are the project timeline and milestones appropriate and realistic for the proposed research and clinical trial objectives? How adequately does this application address Good Clinical Practices (GCP), Good Laboratory Practices (GLP), and Good Manufacturing Practices (GMP) compliance? For multi-site trials proposed in the UH3 phase, how well does the applicant plan to leverage the resources of the ICN Core?

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?

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Specific to this FOA:

How appropriate are the collaborative objectives in the UG3 phase led by institutions that can significantly contribute to the advancement of the cell therapy field? If proposed, how appropriate are the administrative, data coordinating, enrollment, and laboratory/testing centers for the trial proposed? How well does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? How appropriate are the plans to add or drop enrollment centers, as needed? If multi-sites/centers, how adequate is their evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and (4) operate within the proposed organizational structure?

Additional Review Criteria

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

Milestone plan

• To what extent do the proposed milestones provide sufficient detail for the planned tasks?
• To what extent do the proposed milestones have quantitative criteria that will facilitate making go/no go decisions?
• To what extent do the proposed timelines demonstrate the feasibility of achieving the milestones?
• As reflected in the milestone plan, how strong is the applicant’s understanding of the regulatory requirements of the project (e.g., FDA pre-submission meeting(s), submission of an IDE, etc.)?
• How appropriate are the milestones for the UH3 phase and do they reflect the ability to accrue the appropriate population to meet the projected accrual? Are the milestones appropriate for the proposed correlative/mechanistic studies?

Study Timeline

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by 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 will receive a written critique.

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.

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 National Cancer Advisory Board. The following will be considered in making funding decisions:

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

Recipients 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.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

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.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/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.

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 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

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, 2 CFR Part 200, 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 recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH's 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

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

The PD(s)/PI(s) of each award will have the primary authority and responsibility for the project as a whole, including determining research approaches, designing protocols, setting project milestones in consultation with NCI staff, ensuring scientific rigor, conducting specific studies, analysis and interpretation of research data, and preparation of publications.

Specific rights and responsibilities will include the following:

• Conducting the scientific research in the project, reporting progress and milestones or objectives to NCI staff, reporting results to the scientific community, and disseminating approaches, methods, models, and tools broadly;
• Assuming responsibility and accountability to the applicant organization officials for the performance and proper conduct of the research and administrative functions supported under this Funding Opportunity Announcement in accordance with the terms and conditions of the award, as well as all pertinent laws, regulations, and policies;
• Participating in a cooperative, interactive, and collaborative manner with NCI staff, other Can-ACT investigators, and one another to maximize the impact of the Can-ACT and meet Program goals and objectives;
• Serving as voting members of the Can-ACT Steering Committee (Can-ACT SC or SC) that is responsible for the governance of Can-ACT activities (as described below);
• Accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the Can-ACT SC;
• Maintaining the confidentiality of the information developed or handled by the Can-ACT, including, without limitation, unpublished data, protocols, data analysis, confidential exchanges between members of the Can-ACT, as well as any confidential information received by third-party collaborators;
• Facilitating the public release and dissemination of results, data, reagents, models, technologies, and other products generated through this award in a timely manner. All PDs/PIs are expected to share data and resources generated through this award in accordance with the approved plan for making quality-assured data and materials available to the scientific community and the NIH as written in the final version of the grant application, and consistent with sharing policies and recommendations developed and approved by the SC, NIH sharing policies, and the goals of the FOA;
• Ensuring that any industry collaborations should be governed by a research collaboration agreement with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH policies and procedures, and any policies and procedures developed by the SC;
• Complying with OHRP and FDA regulations concerning the protection of human subjects if the project involves human subjects and/or NIH-defined clinical research;
• Operating in accordance with processes and goals as delineated in the Funding Opportunity Announcement;
• Operating in accordance with processes, goals, and policies established by the SC to the extent of applicable grant regulations;
• Attending an initial face-to-face Kickoff Meeting of the Can-ACT PDs/PIs, followed by one Can-ACT investigator meeting annually; and
• Adhering to a Network Communication Plan: A consensus Communication Plan will be drafted by the Can-ACT SC during the kickoff meeting of the Can-ACT. This plan will clearly spell out interactive requirements that all Can-ACT investigators are expected to follow, including:
  • Participation in regular conference calls with fellow Can-ACT colleagues through contribution to various sub-committees and working groups;
  • Participation and presentation of findings at the Can-ACT Annual Investigators' Meeting;
  • Coordination of efforts with other members of the Can-ACT;
  • Jointly publishing on Can-ACT collaborations and scientific achievements in a timely manner; and
  • recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

NCI program staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. The substantially involved NCI program staff member(s), acting as Project Scientist(s), will coordinate in a centralized fashion various activity of the recipients. Specific responsibilities of the NCI Project Scientist(s) will include, but will not be limited to:

• Advising the recipients on specific scientific issues as well as programmatic priorities;
• Assisting the Network recipients as a liaison in stimulating their broader interactions with other NCI and NIH programs to disseminate results and outcomes and effectively leverage existing NIH/NCI resources and infrastructures (e.g., databases);
• Informing the Network about pre-clinical resources available through the NCI such as the NExT program (resources for GMP manufacturing, viral vectors, and toxicology);
• Participating in the development and evaluation of trans-Network activities;
• Assisting in avoiding unwarranted duplications of effort across the Network;
• Monitoring the operations of the UG3/UH3 recipients and making recommendations on overall project directions;
• Approving transition from UG3 to UH3 phase;
• Facilitating collaborations with other scientists having relevant research projects or technology platforms;
• Reviewing the progress of individual UG3/UH3 recipients and specific activities shared among them;
• Helping coordinate collaborative research efforts that involve multiple recipients including approving restricted supplemental funding to UG3/UH3 recipients for collaborative activities;
• Co-organizing and participating in Can-ACT SC meetings;
• Assisting in the management of the Can-ACT SC including the development of draft sharing and operating policies that are in accordance with NIH guidelines;
• Reviewing the compliance of Can-ACT recipients with the recommendations developed by the SC; and
• Coordinating external evaluation of the Can-ACT.

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

The NCI reserves the right to terminate any Can-ACT award in the event of: (1) a substantial shortfall in accomplishing the management goals and responsibilities as stated in the reviewed application; (2) a failure to meet the Can-ACT policies and procedures; (3) substantive changes in the management of the Can-ACT award that is not in keeping with the objectives of the FOA; and/or (4) failure to make substantial progress towards milestones keeping in mind the agreed upon go/no go decisions.

Additionally, an NCI Program Director acting as the Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility

The Can-ACT Steering Committee (Can-ACT SC or SC) will serve as the main governing body for the Can-ACT. The U24 Can-ACT Coordinating Center (CC) will facilitate SC activities.

Applicants should familiarize themselves with the functions of the Can-ACT CC (Companion RFA CA-22-030). Briefly, the CC will have the following functions:

• Form a Steering Committee for Can-ACT Network;
• Coordinate solicitation and evaluation of administrative supplements;
• Coordinate with ICN Core to achieve multi-site clinical trial coordination, data collection, harmonization, quality, and sharing;
• Provide overall guidance for the further development of the ICN Core and Can-ACT Network through the Steering Committee; and
• Coordinate and organize meetings for the UG3/UH3 centers.

Steering Committee

The Can-ACT Steering Committee will serve as the initiative’s main governing board of the Can-ACT. The Steering Committee will be jointly established by the PDs/PIs from each UG3/UH3 recipient site, the PD/PI from the Can-ACT-U24 Coordinating Center, a representative of the ICN Core, and NCI-designated staff members. The Can-ACT Steering Committee will provide strategic coordination for cross-site activities. The Steering Committee will hold monthly meetings to share ongoing work, discuss current challenges, provide overall advice on future research directions, and foster the exchange of ideas, data, and collaborations across the Network.

Voting members of the Can-ACT Steering Committee will include:

• One representative from each UG3/UH3 project award (a PD/PI or a designated senior investigator) who will have one vote;
• One representative from the U24 (a PD/PI or a designated senior investigator) who will have one vote; and
• NCI Program Officers and Project Scientists will have voting privileges. The ratio of NIH Project Scientists votes to recipient votes will be adjusted to ensure the ratio does not exceed 1:3.

Non-voting members of the Can-ACT Steering Committee will include a representative of the ICN Core. The Can-ACT Steering Committee may decide to add non-voting members as needed, e.g., associate members, patient advocates and/or scientific experts.

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

• Recommending research topics to be solicited by the U24 site for the eventual awarding of administrative supplements;
• Encouraging the use of the ICN Core;
• Encouraging and fostering collaboration and research data sharing among network members;
• Evaluating progress at network sites and making recommendations to NCI officials for expanding or reducing areas of research focus;
• Providing overall guidance for the use and further development of the ICN Core;
• Providing guidance to NCI regarding the use of supplemental funds;
• Establishing network policies and procedures;
• Establishing policies and procedures for collaborative projects, and protocols;
• Advising the Coordinating Center regarding the formulation of policies and procedures for data management, harmonization, and sharing;
• Identifying impediments to success and implementing strategies to overcome them;
• Identifying opportunities for sharing techniques, materials, information, and tools;
• Ensuring the Can-ACT leverages existing NIH resources and programs;
• Evaluating collaborative activities, and providing feedback to the NCI Program Staff; and
• Serving as a hub for a broader outreach to the entire extramural research community investigating adaptive cell therapies in solid tumors.

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

The Steering Committee will formulate strategic decisions and procedures for Network-wide activities. The Can-ACT recipients will be required to accept and implement these decisions and policies to the extent consistent with applicable grant regulations. All SC scientific and policy decisions and recommendations that require voting will be based on a majority vote. The Can-ACT Steering Committee will be constituted at the initial Can-ACT meeting and will meet regularly (monthly or quarterly), including at least once in-person during the annual Can-ACT Investigators Meeting. The chairperson of the Can-ACT Steering Committee will be elected from the representatives of all recipients and is responsible for coordinating the Can-ACT activities with Can-ACT Coordinating Center. The Steering Committee may also choose to replace the Can-ACT Steering Committee chairperson at any time based on poor job performance or failure to follow the relevant procedures and guidelines.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the SC 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 recipient. This special dispute resolution procedure does not alter the recipient'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.

Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

3. Reporting

When multiple years are involved, recipients 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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

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

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

Section VII. Agency Contacts

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

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: [email protected] (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: [email protected]

Kasia Bourcier, Ph.D.
National Cancer Institute (NCI)
Telephone: 202-657-7589
Email: [email protected]

Zhang-Zhi Hu, M.D.
National Cancer Institute (NCI)
Telephone: 240-276-6622
Email: [email protected]

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: [email protected]

Section VIII. Other Information

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

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.