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

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

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

This funding opportunity Announcement (FOA) solicits applications for Cancer Immune Monitoring and Analysis Centers (CIMACs) that will serve as laboratory resource conducting correlative studies in clinical trials involving cancer immunotherapy. The CIMACs activities will be facilitated by the Cancer Immunologic Data Commons (CIDC) (to be supported by the companion FOA (RFA-CA-17-006) through biomedical informatics and information technology methodologies suitable for immune-related biomarkers. Together, the CIMACs and the CIDC will be the primary units of the CIMACs-CIDC Network. CIMACs-CIDC Network is intended to serve as infrastructure for correlative studies in NCI-sponsored clinical trials involving cancer immunotherapy to address the critical importance of biomarkers in management of cancer patients.

Specifically, the Network is intended to address scientific and technical aspects of correlative studies across the NCI-supported early Phase (1 and 2) clinical trials in immunotherapy. Each Center within the Network will encompass a multidisciplinary group with basic, clinical, and computational research expertise. Each CIMAC will offer a wide range of molecular and cell-based analyses using state-of-the-art platforms that will lead to informative biomarker tests to tailor immunotherapy to individual patients. The long term goals are to identify molecular biomarkers that define immune response categories to: (1) predict the likelihood of benefit or toxicity from therapies; (2) help develop rational combination therapies to overcome intrinsic or acquired resistance; (3) aid in understanding resistance mechanisms; (4) provide monitoring strategies; and (5) evaluate target inhibition via pharmacodynamic biomarkers. An additional goal for the Network is to advance biomarker development by establishing and promoting public access to data through a controlled access portal.

Through these collaborative efforts, CIMACs-CIDC Network can accelerate the integration and translation of important research findings generated by individual laboratories in clinically-based studies into applications to enhance efficacy of immunotherapy to benefit patients.

Immunotherapies-promises and challenges. Immunotherapies have emerged as highly promising approaches to treat cancer patients. For example, there have been many clinical successes using immune checkpoint antagonists, including antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) and its ligand, PD-L1. Several checkpoint inhibitors demonstrated significant clinical benefit in cancer patients with tumors of different histologies including melanoma, non-small cell lung cancer (NSCLC), bladder cancer, and renal cell carcinoma (RCC). Some of these inhibitors have been approved by the FDA.

However, the clinical efficacy is limited to a minority of cancer patients. Thus, new approaches to improve the efficacy of immunotherapies for most patients are critically needed. Strategies to improve the efficacy of immunotherapy rely on both an enhanced understanding of the tumor/immune interface at the cellular and molecular level and an ability to select appropriate patients for a specific immunotherapy agent or combination therapy. Optimized biomarker strategies could help elucidate both of these areas and allow cancer immunotherapy to be tailored to the individual patient's disease.

Critical role of biomarkers in optimizing immunotherapeutic strategies. Various experimental findings point to the value of biomarkers for the individualized selection of immunotherapy. For example, high expression levels of PD-L1 (PD-1 ligand) in tumor tissue are associated with a higher likelihood of clinical benefit in NSCLC patients treated with anti-PD-1 checkpoint inhibitors. These data led to the FDA approval of the immunohistochemistry (IHC)-based assay for PD-L1 as a companion diagnostic to one of the PD-1 inhibitors. However, the clinical utility of the PD-L1 IHC assay to predict patient benefit is limited due to technical and biological pitfalls of the biomarker testing in different laboratories. Different IHC assays for PD-L1 use different monoclonal antibody (MAb) clones, different platforms and scoring systems and different cut-points for positivity. Consequently, different methods to assess PD-L1 using different tests make it difficult to compare results across trials. Contradictory data from clinical trials of PD-1 blockers have been reported.

Other biomarkers associated with patient's responses to checkpoint inhibitors have also been reported, including increased peripheral blood absolute lymphocyte count, up regulated T-cell activation markers, and inflammatory gene signatures in the tumor microenvironment, tumor infiltrating lymphocytes and circulating myeloid-derived suppressor cells. A recent observation also suggests that higher mutation load in the tumor and expanded T-cell receptor clonality are associated with responsiveness to PD-1/PD-L1 blockade. However, these biomarkers also suffer from similar issues to the PD-L1 marker and clinical utility has been limited by lack of standardized assays.

Although various immune biomarkers are being monitored in immunotherapy clinical trials, the technologies/assays used and data reporting procedures are not consistent. This situation often hampers data reproducibility among laboratories, which may prevent meaningful interpretations across studies. In addition, most of the assays used involve high-throughput multi-parametric "signatures" that typically require considerable statistical and bioinformatic efforts for proper algorithm development and robust data interpretation. Requisite capabilities may not be available to all investigators assaying immune biomarkers and are not readily being accomplished in the traditional academic or clinical laboratory due to resource constraints. In addition, there is no standing system that can easily integrate analyses across NCI-supported clinical trials.

NCI efforts toward personalized immunotherapy approaches. The NCI recognizes the challenges noted above and the need for systematic investigations focused on translational studies associated with clinical trials in immunotherapy. These studies require focused and coordinated efforts with access to resources including instrumentation and multidisciplinary expertise in biomarker testing and analysis. Accordingly, the Network composed of Cancer Immune Monitoring and Analysis Centers (CIMACs) and the Cancer Immunologic Data Commons (CIDC) to support high-quality correlative studies in NCI-sponsored early phase (Phase 1 and Phase 2) clinical trials is proposed.

Since 2010, the NCI Division of Cancer Treatment and Diagnosis (DCTD)-supported clinical trial networks have activated more than 90 immunotherapy clinical trials. These trials test immune agent monotherapy or novel combinations. The studies have ranged from first-in-human Phase 1 trials to randomized Phase 2 and Phase 3 trials in neoadjuvant, adjuvant as well as advanced tumor settings. Multiple immunotherapy agents are being tested, including agents targeting CTLA-4 and PD-1 and PD-L1, as well as other checkpoint modulators, bispecific antibodies, oncolytic viruses, cancer vaccines and cytokines.

Importantly for this FOA, most of the NCI-sponsored trials have mandatory collection of 'baseline' tissue and blood. Many early trials (Phase 1 and Phase 2) also mandate 'on-treatment' biopsies. Thus, the NCI-supported clinical trial networks represent an optimal setting to incorporate biomarker questions, particularly in the early phase trials that offer the ability to detect signals of efficacy for immunotherapy agents. This FOA will require that the CIMACs align with one or more NCI-supported clinical trial networks/consortia. This partnership will assure that comprehensive characterization of candidate biomarkers using well-controlled molecular approaches will be integrated into NCI-supported early phase immunotherapy trials and thereby accelerate progress towards the goal of selecting appropriate patients for these treatments.

Proposed Centers for the Network must include the following main attributes (for additional details, please see Section IV.2 Content and Form of Application Submission).

Overall Focus:

The Cancer Immune Monitoring and Analysis Centers (CIMACs) supported under this FOA, in parallel

with the Cancer Immunologic Data Commons (CIDC) (to be supported by the companion FOA, RFA-

CA-17-006) with its focus on bioinformatics will be main units of the CIMACs-CIDC Network. Since CIMACs will interact closely with CIDC, it is imperative that all CIMAC applicants familiarize themselves with CIDC RFA-CA-17-006.

The overall goal for the Network is to advance translational research efforts using biomarkers to aid in the further development of cancer immunotherapy. Specifically, this FOA will support the studies on: predictive biomarkers to select patients who are most likely to benefit from a particular immunotherapy; and pharmacodynamic biomarkers to improve understanding of the tumor-immune system interface (critical to optimal development of immunotherapy approaches and rational design of therapeutic combinations).

The CIMACs will function as platforms for deep molecular characterization of tumor and immune profiling. The individual studies in which biomarkers will be incorporated will be led by NCI-supported clinical trials groups. The role of CIMACs in these efforts is expected to include such aspects as:

• Collaboration in the selection of appropriate biomarkers;
• Performing the range of laboratory analyses needed using clinical specimens; and
• Participation in the appropriate integrative/correlative data collection (to be led by CIDC).

The CIDC will work closely with each CIMAC for standardization of data collection methods to enable

integration across the studies within the Network and with public databases outside the Network

(e.g., clinical, immunology or genomic databases); and facilitate secondary analyses across studies

carried out in the CIMACs.

Overall, the CIMACs will be expected to define patient responses to immunotherapy in a way that will help identify clinically-informative biomarkers for future validation in late-phase clinical trials. (Note: Although clinical validation will be required for clinical decision-making assays, this aspect remains beyond the scope of this FOA).

CIMACs Expectations and Requirements.

Each CIMAC supported by this FOA should be capable of conducting systematic investigations that require coordinated efforts with access to multidisciplinary expertise of clinical and biomarker experts, availability of high content assay platforms, as well as biostatistics and computational resources for data analysis and interpretation.

Each Center will be required to:

• Conduct biospecimen analyses using well-established fit-for-purpose assays and the state-of-the-art assay platforms in specimens from clinical trials to develop molecular signatures that define immune response categories;
• Analyses should focus on the tumor-immune system interface, utilizing a variety of molecular and cellular platforms;
• It is expected that certain well-established analyses will be offered by all Centers [e.g., flow cytometry, immunohistochemistry (IHC)];
• Other assays (e.g., specific high-throughput and high-content assays) requiring availability of sophisticated techniques and equipment may be performed only in a single CIMAC that has the capacity and houses respective unique platform(s). If such analysis is needed, it will be assigned to the CIMAC that has the unique capability even if specimens from a given clinical trial will be primarily analyzed by another CIMAC;
• Each CIMAC should have appropriate biostatistics and computational capabilities for data collection and analysis for each analytical platform. Each CIMAC should also have an ability to perform complex bioinformatics analyses and interpretation of -omics data in conjunction with clinical data;
• CIMACs must be able to submit data sets from individual correlative studies to CIDC;
• CIMACs will also be required to share resources, reagents, methods, and SOPs as appropriate, with other awardees across the network; and
• Each awardee will work together with other CIMACs-CIDC Network participants to build a centralized resource based upon common data standards, standard operating procedures (SOPs) for validated assays use, and to contribute to the creation of an immunoprofiling database for broader dissemination.

The examples of well-established assays commonly used for profiling of the tumor and immune response include platforms for:

• Genomic characterization of the tumor and microenvironment in the context of response and resistance to immunotherapy;
• Characterization of molecular requirements (e.g., T cell epitopes) for effective immune response;
• Functional characterization of immune elements, especially T cells; and/or
• Phenotypical characterization of cellular and soluble factors in blood and serum as well as tissue specimens from patients in immunotherapy trials.

The assays/techniques to be employed in the Centers may include, but are not limited to:

• Multispectral fluorescence activated cell sorting (FACS);
• Multicolor IHC and multiplexed immunofluorescence (IF);
• DNA sequencing;
• T-cell and B-cell epitope prediction;
• T-cell and B cell receptors (TCR and BCR, respectively) sequencing;
• Transcriptional profiling (e.g., nCounter analysis system for gene expression profiling/pathway activation/immuno panel etc., RNA-seq);
• Mass cytometry (Cytometry by Time-Of-Flight, CyTOF);
• IFN gamma/granzyme B (enzyme-linked immunospot, ELISPOT);
• Circulating tumor DNA (ctDNA);
• Multiplex enzyme-linked immunosorbent assay (ELISA); and
• Peptide-major histocompatibility complex (MHC) multimers.

Additional Requirements

To be responsive to this FOA, each proposed CIMAC must have the following capabilities and must meet the requirements listed below:

• Infrastructure, instrumentation, quality assurance processes, etc., must be in place from the start of the project period to conduct the proposed analyses;
• Applicants are expected to have extensive expertise in developing and using rigorously controlled assays for unbiased and well defined biomarkers and in standardizing the proposed platforms for analysis of specimens from clinical trials. In these regards, all CMACs will be expected to have:
• Ability to ensure rigor and reproducibility in all types of analyses;
• Ability to prioritize a comprehensive unbiased approach data for locking down the assay for testing in additional samples; and
• Facilitate availability of reference materials and key reagents for the Network studies;
• The Centers should have the capacity to carry out the necessary validation steps for candidate assays and perform assays for integral biomarkers (for treatment eligibility) in a Clinical Laboratory Improvement Amendments (CLIA)-compliant laboratory that may need to be performed under an Investigational Device Exemption (IDE) from the FDA.

Sources of Clinical Specimens for CIMACs

In their role as infrastructure resources to clinical trials networks, the Centers will be required to work closely with one or more NCI-supported clinical trials networks. The applicants team should have a record of participating in multi-center trials or collaborating (especially on correlative study design and research) with at least one of the networks or consortia of the NCI supported clinical trials or with other multi-center trials. Each CIMAC will be aligned with one or more NCI-supported clinical trial networks (listed below) to serve as the CIMAC's primary partner(s).

• National Clinical Trials Network (NCTN);
• Experimental Therapeutics Clinical Trials Network (ETCTN);
• Cancer Immunotherapy Trials Network (CITN);
• Pediatric Brain Tumor Consortium (PBTC) Pediatric phase I and II Network; and
• Adult Brain Tumor Consortium (ABTC).

The alignment of individual CIMACs with specific NCI funded clinical networks will be negotiated between the NCI and the CIMAC recipients with the goal of assuring coverage of all NCI-supported early phase immunotherapy trials in NCI networks and optimized usage of scientific and technical capabilities of each CIMAC.

The specimens for CIMAC biomarker assays will be derived from Phase 1 and 2 immunotherapy trials. In the event of a combined Phase 2/3 trial, the CIMAC award will support only the Phase 2 component. Phase 3 trials are outside the scope of this FOA. If there is a need for correlative studies for the Phase 3 segment, additional funds would have to be obtained from outside the CIMACs award for such study.

Immunotherapy trials conducted by investigators via other NCI-sponsored research grants will be eligible to apply to have their biomarker studies conducted by the CIMACs. The CIDC will develop an application process and applications will be prioritized by the CIMACs-CIDC network governing body, the Laboratory Coordinating Committee (LCC, see below). Examples of NCI-supported clinical trials from outside the established networks/consortia include those conducted under research grant mechanisms.

Samples can be retrospective from completed or ongoing trials, prospective or combination of prospective-retrospective trials samples collected and submitted to the CIMACs (See Section IV.2: Research Strategy). It is anticipated that each CIMAC will perform comprehensive immunoprofiling analyses for a minimum of 120 biospecimens from patients in immunotherapy clinical trials. It is expected that up to one third of the expected biospecimens will reflect correlative studies requested by investigators from NCI-supported clinical trials that are outside of the NCI clinical trials networks/consortia that will serve as the primary partners of the CIMACs. CIMACs will be expected to collaborate with all their clinical trials partners to develop the systems to receive and track requests for immune marker analysis, to log samples from clinical trials, to provide shipment information, and to return unused specimens to appropriate clinical trials tumor banks.

Non-responsive Studies

The following types of studies are beyond the scope of the FOA:

• Biomarker discovery;
• Development of new assays; and
• Studies proposing a clinical trial.

Applications proposing such studies will be viewed as non-responsive and will not be reviewed.

Governance:

The CIMACs-CIDC Network will be governed by a Laboratory Coordinating Committee (LCC). Details on the composition and functions of LCC are provided in Section VI.2 Administrative and National Policy Requirements, Cooperative Agreement Terms and Conditions.

External Evaluation of the CIMACs Network

CIMACs awardees will be expected to participate in an external evaluation process that will be coordinated by the NCI Scientific staff. This evaluation will largely be based on the overall progress towards achieving the scientific goals of the entire CIMACs-CIDC Network Program.

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

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

Higher Education Institutions

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

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

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

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

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

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

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

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

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

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

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

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

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

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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

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

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

The letter of intent should be sent to:

Magdalena Thurin, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5973
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.

Facilities and Other Resources:

Describe the infrastructure and available resources to support research activities at the CIMAC. Specifically, provide information on the available instrumentation (indicate any unique instruments/methods) and assay capabilities. For each assay or type of analysis, provide current and achievable rate of sample processing (e.g., number samples per month). Provide such information for all performance sites that will be included in the multi-site application (if applicable).

Other Attachments:

Attachments listed below must be provided or the application will be incomplete and will not be peer reviewed. Upload these attachments using the filenames indicated.

Attachment I. Biospecimen-related Standard Operating Procedures (use filename "Biospecimen SOPs"). Summarize biospecimen-related SOPs that are already in use or are ready to be implemented. Include SOPs for collection, processing, storage and shipping of clinical specimens that ensure stabilities and other required qualities of molecular analytes in the specimen at the time of analyses. The outlines should provide sufficient information for reviewers to assess the quality of these SOPs and should refer to the availability of the complete documents with detailed instructions for specific uses.

Attachment II. Assay Validation Procedure and Data (use filename "Analytical Validation"). Provide (in a tabular form) a summary for the proposed, analytically-validated assays. Include data documenting adequate assay performance characteristics in terms of: (i) accuracy; (ii) precision; (iii) analytical sensitivity; (iv) analytical specificity including interfering substances; (v) reportable range of assay results for the assay system; (vi) reference intervals (normal values) with controls and calibrators; (vii) standardization, harmonization, reproducibility and ruggedness of analytical performance if the assay is to be performed in multiple laboratories; (viii) establishment of appropriate quality control and improvement procedures; and (ix) any other performance characteristics required for assay performance with determination of calibration and control procedures. The test methods proposed should be well documented. Evidence that provides a high degree of assurance that a specific method, and the instruments included in the method, will consistently yield results that accurately reflect the quality characteristics of the product tested should be provided.

Attachment III. Team's Collaborative Clinical Trials (use filename "Clinical Collaborations"). Document the collective team capabilities for the participation in clinical trials. For example, list ongoing and/or past collaborative clinical trials, preferably with at least one of the networks or consortia of the NCI supported clinical trials. Provide key details such as correlative study designs and types of assays. used, etc. As applicable, the documentation under this attachment may include letters from such collaborating clinical networks documenting the applicants' record of participation.

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

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

The budget should address the following FOA-specific items:

• PD/PI Effort Commitment. Any PD/PI (whether designated as contact or not) must commit a minimum of 1.2 person-months effort per year to the award. This commitment cannot be reduced in later years of the award. Note that this is a minimum effort level that should be increased as appropriate to meet the needs of the work.
• Under Personnel Costs, list all personnel involved with the anticipated effort levels for the Center operation. In the Budget Justification provide break down for the following two types of efforts:
• Effort levels and salary support reflecting the personnel costs portion of the biospecimen analysis costs, such as study design personnel, statistician effort, laboratory supervising and technical staff, etc. (see note on Specimen Analysis Costs below); and
• Base effort levels for resource function (i.e., efforts that will be needed regardless of the number and types of specimens processed in any period by CIMAC). The allowable "fixed" efforts may correspond to salary support for: PD/PI (as instructed above), personnel needed for the resource computational and biostatistical function, a technician effort to regularly maintain instrumentation used for the biospecimen analysis (but only to the extent not covered by other sources), or laboratory personnel involved in analytical validation of some assays (if such validation is proposed).
• Under "Other Direct Costs", list:
• The costs of supplies (e.g., reagents, consumables) and other expenses needed for the biospecimen processing and performance of the assays (see note on Specimen Analysis Costs below);
• A modest level of supplies and other fixed expenses unrelated to the number and types of specimens processed in any period by CIMAC. These costs (which should not exceed approximately $30,000 a year) may include, for example, supplies needed for analytical assay validation (if proposed), minor instrumentation upgrades, replacement of small equipment, repairs, etc. Requests for capital equipment (defined as items above $5,000-unit cost) are not allowed.
• Note on Specimen Analysis Costs and Budget Justification.
• All elements of costs related to biospecimen analyses (personnel and non-personnel) must be calculated and budgeted assuming the conduct of comprehensive correlative analyses (i.e., using a panel of several complementary assays for each biospecimen) for the projected number of 120 biospecimens per year (approximately 80 specimens from the primary partners--NCI clinical trials networks--and the remainder from other non-network clinical trials). The projected number of 120 specimens per year for comprehensive analysis by each CIMAC is estimate and actual number of specimens received and processed by a given CIMAC for analyses may vary somewhat. (Note: Depending on the actual number of specimen processed, the award may be adjusted accordingly.)
• In Budget Justification provide unit costs per assay for each assay type proposed and explain how these unit costs are calculated.
• Specialized assays reflecting the CIMAC's unique technical capabilities: Applicants for a CIMAC that will have a capability to conduct a unique assay type (not likely to be available from other CIMACs) should expect that the LCC may ask them to perform, if appropriate, such unique type of analysis for specimens coming from clinical trials other than the trials for which the given CIMAC will serve as the primary resource. If applicable, applicants should include in Budget Justification their estimate of the number of such assays per year that the entire CIMACs-CIDC network might need.
• Travel Funds. The budget should also include travel funds for PD(s)/PI(s) and other senior investigators (up to three people) to attend the annual Network and LCC meetings and participate in other network-related activities.

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: Describe the specific aims of the proposed Cancer Immune Monitoring and Analysis Centers (CIMAC) and identify the area of translational research focus.

Research Strategy: Provide an overview of the proposed CIMAC. Address all the specific aspects indicated below using the sub-sections as defined:

Sub-section (A) Significance and Innovation: In addition to standard items address all the following specific aspects:

• Describe how the Center will support the overall mission of the CIMAC and the Network and explain the anticipated contributions of the proposed CIMAC to the understanding of the tumor-immune system interface that can inform individualized approaches for immunotherapy of cancer patients;
• Outline the specific aims for the CIMAC explaining how the inclusion of the proposed assays may benefit the studies of biomarkers for immunotherapy and, eventually, advance the concept of personalized medicine in cancer immunotherapy;
• Describe how the CIMAC and the clinical investigators teams envisage the collaborations with other CIMCs and CIDC;
• Describe the key technical capabilities and the infrastructure that the Center can provide to support innovative research for biomarker testing, including any novel, validated and standardized approaches and/or methods to understand the interaction of the tumor and immune system; and
• Highlight any new, innovative concepts proposed to assess the biomarker candidates for predicting or monitoring responses to cancer immunotherapies.

Sub-section (B) Investigative Team.

• Summarize the major collective strength of the team in the proposed area of scientific and technical expertise;
• Without repeating information from individual biosketches, explain how the specific expertise of team members (e.g., cancer biology and immunology, pathology, genomics, biomarker experts, assay developers, computational biology, biostatistics, others) will be used to advance the proposed laboratory translational research program;
• Describe the team experience in research related to clinical trials, especially conducting correlative studies;
• Describe the environments (e.g., academic or other research) of the research team members and how they will support the mission of the proposed Center; and
• Describe critical experience of the PD(s)/PI(s) and the team in coordinating multidisciplinary and multi-institutional programs;

Sub-section (C) Approach. In addition to standard items address all the following specific aspects:

• Outline how the proposed Center will serve as a resource for immunotherapy clinical trials in terms of providing highly specialized and comprehensive molecular analyses and immunoprofiling using appropriate clinical biospecimens;
• Provide key information on assays proposed, including rationale for the proposed assay platforms and criteria for prioritization of assay selection for specific types of studies anticipated;
• Note any approaches, equipment etc., including specialized assays reflecting the CIMAC's unique technical capabilities that may be of broader interest to various immunotherapy clinical trials but may not be available from other CIMACs;
• Provide timeline for crucial elements of the CIMAC operation (e.g., readiness for sharing SOPs for specimen processing, platform availability etc.). If an assay proposed still requires analytical validation or standardization, provide plans to complete such activities;
• Discuss approaches to update the Center capabilities with improved, emerging technologies and more sophisticated methods that could benefit biomarker development and testing; and
• Study design and scientific rigor. Under a separate heading "Approach to Study Design and Scientific Rigor", explain how you will approach the design of relevant correlative research (which CIMAC awardees will be doing in collaboration with their clinical partners). The description could be based on prior work by applicants or may reflect a generalized proposed workflow, decision tree, steps, and considerations that will be used. In either case, explain how you will interrogate the proposed biomarkers to generate results that are meaningful and can inform early phase immunotherapy clinical trials. A clear rationale should be given for the details of experimental design and technical methodologies proposed. The description must address statistical considerations and approaches to data analyses. Under this heading address also the general aspects of scientific rigor:
• Describe how the experimental design and methods proposed will achieve robust and unbiased results; and
• Explain how relevant biological variables are factored into research designs and analyses.

Sub-section (D) Computational and Biostatical Function:

• Outline the organization and function of the biostatistics and computational portions of the CIMAC;
• Incorporate the plans for specific computational activities including data analysis and developing algorithms for multi-parametric assays (if appropriate) for correlation with clinical outcome;
• In addition, address the system for tracking of specimens and analysis steps. Usage of the software(s) allowing searches on multiple parameters utilizing comparison elements to find a set of samples and associate the specific analyses is required. The advanced search parameters should also be saved as commonly executed queries so that they can later be accessed by all or specific users including the CIDC staff. Each Center should be able to monitor the sample and the results of the analyses via tracking; and
• Potential timeline for crucial elements (e.g., software availability for data analysis, tracking system development etc.).

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• The plan should be consistent with the requirement for all CIMACs to share resources, reagents, methods, and SOPs as appropriate, with other awardees across the network.
• Data Sharing Plan is expected to adhere to the guidelines in the NCI Genomic Data Sharing Policy (https://www.cancer.gov/grants-training/grants-management/nci-policies/genomic-data).
• For research activities using biospecimens from NCI/CTEP clinical trials, Data Sharing Plans must also comply with the following rules:
• If the biospecimens are from a clinical trial that was conducted under a binding collaborative agreement with NCI or a pharmaceutical company (for example, with a company that supplied the drug), data sharing may have to await the timelines stipulated in those agreements. Studies conducted under a NCI/CTEP IND are subject to the terms of the CTEP Intellectual Property (IP) Option (http://ctep.cancer.gov/industryCollaborations2/guidelines_for_collaboration.htm) as well as the terms of the CTEP Collaborative Agreement under which the study is conducted. Similarly, studies conducted under a NCTN Group or Company IND will also be subject to the terms of the agreement between the Collaborators. Any discoveries from research performed on such specimens will be subject to the CTEP IP Option and/or the licensing terms as required by these agreements.

Prior to funding, NCI program staff members may negotiate modifications of data sharing plans with the applicant. Any data sharing plans represent a commitment by the institution (and its subcontractors, as applicable), to support and abide by the plan. The final version of any accepted data sharing plans will become a condition of the award.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by 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.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

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

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

Specific for this FOA: How will the proposed Center activity advance the overall goal of the CIMAC and the Network? Will the CIMAC, as proposed, have meaningful contributions to the understanding of the tumor-immune system interface that can inform research effective individualized approaches for immunotherapy of cancer patients?

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

Specific for this FOA: Are the backgrounds, expertise, and commitments of the PD(s)/PI(s) and other key persons sufficient for the proposed scope of activities and in line with the overall goals of the CIMAC? Is the investigators' team sufficiently well-integrated to work efficiently towards the overarching goals of the Network to improve the understanding of the tumor-immune system interface and, eventually, inform individualized approaches for immunotherapy of cancer patients? How extensive is the investigators' past experience in conducting correlative studies for multi-center clinical trials and/or collaborating on such studies with at least one of the networks or consortia of the NCI supported clinical trials?

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

Specific for this FOA: Does the proposed CIMAC employ novel, validated and standardized approaches and/or methods to understand the interaction of the tumor and immune system? Do the applicants propose new, innovative concepts to assess the biomarker candidates for predicting or monitoring responses to cancer immunotherapies?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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 children, justified in terms of the scientific goals and research strategy proposed?

Specific for this FOA: Given the scientific competencies, technical capabilities, and infrastructure described, will the proposed CIMAC provide scientifically appropriate, efficient, and competent support for correlative studies on biospecimens from immunotherapy clinical trials? Does the Research Strategy (including, specifically, the Sample Study Design) demonstrate an appropriate understanding of how to approach and optimally design molecular characterizations, biomarker monitoring, etc.? Are methodologies appropriate to exploit the biomarker role in the context of its potential to facilitate personalized approaches for immunotherapy? How well does the proposed CIMAC take advantage of multi-disciplinary approaches to promote and advance the understanding of the mechanisms underlying response to immunotherapy approaches? Are mechanisms for facilitating sharing of resources, reagents, methods, and SOPs across the network well-planned or in place as appropriate and consistent with achieving the goals of the Network? Are the timelines well matched with the goal of the Center?

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

Specific for this FOA: How supportive will the scientific environment be for the CIMAC multi-disciplinary research? Is there evidence of sufficient institutional support for the proposed Center in the applicant institution and, if applicable, other participating institutions? Will the activities of the proposed Center be efficiently and well-coordinated (especially if the proposed Center involves multiple institutions)? Is there evidence of ongoing productive interactions among participating investigators/institutions or, if the partnership is new, what is the likelihood that such productive interactions will readily emerge? How well articulated are the intentions/plans to interact with other CIMACs and CIDC? Will the environment of the proposed CIMAC contribute meaningfully to the capabilities of the CIMACs-CIDC Network as a resource for NCI-supported immunotherapy clinical trials?

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

For research that involves human subjects but does not involve one of the six 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 six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

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

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

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

Not Applicable

Not Applicable

Not Applicable

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

Not Applicable

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

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

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

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

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the 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.

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

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

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

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

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

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

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

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

• Determining the CIMAC's directions, coordinating research approaches and procedures, and overseeing the analyses and interpretation of analysis data;
• Overseeing the timely release and sharing of data according to the approved plans;
• Participating in the annual Network Laboratory Coordinating Committee (LCC) meeting, and periodic conference calls organized by the LCC;
• Cooperating with NCI Project Scientists and clinicians in the program, as needed;
• Accepting and implementing all scientific and practical decisions approved by the LCC to the extent consistent with applicable grant regulations;
• Providing information to the NCI Program Directors concerning progress by submitting annual progress reports;
• Preparing for administrative site visits by NCI staff members; and
• Taking advantage of opportunities to collaborate with other CIMACs to advance the Center research effort.

The following additional responsibilities will also apply for each Center awardee:

• Each Center and the entire Network will be the subject to periodic performance evaluation (coordinated by the LCC) and awardees will be expected to participate in these evaluations;
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies; and
• All institutions/organizations participating in a given Center will be expected to exchange with other members of the CIMACs-CIDC Network, as appropriate and needed, scientific expertise, data, research reagents, technical procedures, and/or any other resources resulting from the Center award.

In addition, the awardees must ensure that all the activities under CIDC award are consistent with the following rules and regulations:

• Research projects using biospecimens from NCI/CTEP clinical trials are subject to the requirements in NIH policies for data sharing and public access to publications, listed below, and to any applicable requirements of binding collaborative agreements.
• If the biospecimens are from a clinical trial that was conducted under a binding collaborative agreement with NCI or a pharmaceutical company (for example, with a company that supplied the drug), data sharing may have to await the timelines stipulated in those agreements. Studies conducted under a NCI/CTEP IND are subject to the terms of the CTEP IP Option (http://ctep.cancer.gov/industryCollaborations2/guidelines_for_collaboration.htm) as well as the terms of the CTEP Collaborative Agreement under which the study is conducted. Similarly, studies conducted under a NCTN Group or Company IND will also be subject to the terms of the agreement between the Collaborators. Any discoveries from research performed on such specimens will be subject to the CTEP IP Option and/or the licensing terms as required by these agreements

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

The designated NCI Program staff members of the Laboratory Coordinating Committee (LCC) will have substantial involvement as Project Scientists in the awards under this FOA. The specific roles of the substantially involved NCI staff members include the following activities:

• Serving as members of the LCC;
• Assisting in avoiding unwarranted duplications of effort across the Network;
• Helping coordinate collaborative research efforts that involve multiple Centers;
• Monitoring the operations of the Centers and making recommendations on overall project directions; this activity shall include on-site visits to the Centers;
• Reviewing the progress of individual Centers and specific activities shared among the Centers and CIDC;
• Participating in the development and evaluation of cross-Network activities;
• Co-organizing and participating in the annual LCC meetings;
• Assisting the Network awardees 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); and
• Assisting each CIMAC to assess implementation of SOPs and other quality control/quality assurance measures.

In addition, NCI staff members will be substantially involved in optimizing the usage of CIMACs-CIDC network, including balancing the needs and programmatic priorities for the NCI-supported clinical networks (i.e., the primary clinical partners CIMACs-CIDC Network) versus the requests for biospecimen analyses/correlative studies from other (non-network) NCI-supported clinical trials. In this context, NCI Project Scientists will be in charge of:

• Negotiating with each CIMAC recipient the optimal alignment with specific NCI-funded clinical networks, considering optimized usage of scientific and technical capabilities of each CIMAC and the goal of assuring coverage of all NCI-supported early phase immunotherapy trials in NCI networks;
• Reviewing and approving the activation of clinical and correlative studies associated with the assigned primary clinical partners (i.e. the NCI-supported clinical trial networks); and
• Reviewing the LLC recommendations regarding the prioritized correlative studies for clinical trials protocols associated with the requests from other (non-network) NCI-supported clinical trials and approving the protocols for such correlative studies for activation by CIMACs.

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. Such an individual may also be substantially involved as a Project Scientist.

Areas of Joint Responsibilities include:

The CIMACs Network Laboratory Coordinating Committee (LCC) will serve as the main governing board of the CIMACs-CIDC Network. The LCC will consist of the following voting members:

• The PD(s)PI(s) of each awarded CIMAC (or a PD/PI and a designated senior investigator) who will collectively have one vote for each CIMAC;
• The PDs/PIs of the CIDC (or a PD/PI and a designated senior investigator) who will collectively have one vote for CIDC; and
• The NCI Project Scientists, who will represent three relevant NCI programs (Cancer Therapy Evaluation Program, Cancer Diagnosis Program, and Biostatistical Research Program) and who will collectively have one vote for the NCI.

A chair of the LCC will be selected at the first LCC meeting from the CIMACs-CIDC representatives (the LCC chair cannot be an NIH representative.)

The LCC will meet at least once a year in a face-to-face meeting and as needed by teleconferences. (These meetings and other LCC activities will be logistically supported by CIDC.)

LCC may invite additional individuals as non-voting members, as needed, e.g., serve in an advisory capacity. These additional members may include other NCI and NIH Program Staff members and/or Program Staff members from other Federal agencies.

LCC will have the following primary responsibilities:

• Overseeing the overall Network program and reviewing its research progress;
• Evaluating and prioritizing all clinical protocols and correlative studies associated with the requests from outside the primary partners of the CIMACs and making recommendations to CTEP regarding activation of high priority correlative studies protocols and their assignment to specific CIMACs;
• Developing procedures for soliciting and evaluating ideas to analytically validate biomarker assays across the Network as well as criteria for their prioritization and approval;
• Making recommendations for termination of analyses that become unpromising or unproductive;
• Developing the agenda for the annual LCC and Network investigator meetings; and
• Making other recommendations, as appropriate, for specific actions, e.g., procedure standardization, to be adapted by the Network and/or individual awardees.

Dispute Resolution:

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

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

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726

Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)

Telephone: 301-710-0267

For general inquiries regarding this FOA:

Magdalena Thurin, Ph.D.)
National Cancer Institute (NCI)
Telephone: 240-276-5973

Email: [email protected]

For inquiries regarding the NCI-supported Clinical Trials Networks and Consortia:

Helen Chen, M.D.
National Cancer Institute (NCI)
Telephone: 240-276-6106
Email: [email protected]

For inquiries regarding other "non-network" NCI-supported immunotherapy clinical trials:

Minkyung (Min) Song, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6139
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]

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.