NExT Application Instructions

Please note that a NExT proposal is NOT a grant application. Rather, a NExT proposal is an application to gain access to scientific capabilities and resources available to the NCI with the goal of moving promising anti-cancer concepts and novel agents into clinical testing.

Applications to the NExT Program are evaluated for scientific merit, feasibility, novelty, clinical need, and alignment with NCI mission. Special consideration will be given to applications that address unmet needs in oncology, including approaches to exploit “undruggable” drug targets, orphan malignancies, and pediatric cancers.

General Guidelines

Standard Concept

The NExT Concept Application is the typical of application type submitted for discovery and development proposals. The concept application includes 5 sections as described in detail below, with additional material uploaded as appendices. Please use the NExT Concept Application Template (see templates at the bottom of this page) to craft the 5-page proposal narrative. The NExT Concept Application template, and other templates, are available in proposalCENTRAL when the cycle opens.

Multi-Agent Concept

Instances where multiple agents from an investigator are seeking clinical evaluation should utilize the NExT Concept Application for multiple agents. This application follows the same format but provides applicants an expansion on page limit to describe each agent and how they will provide benefit against the cancer target(s) and indications, while considering patient stratification.

Formatting

Formatting guidelines require that applicants follow PHS 398 font guidelines (i.e., Arial, Helvetica, Palatino Linotype or Georgia typeface, 11 point or larger, and that all documents are uploaded as PDF files, making sure that all PDF files are not password protected, before submission).

The Biosketch template is available as a download at the bottom of this page. For applicants that are unfamiliar with the NIH Biosketch format, please download the sample NIH Biosketch.

What to include

At a minimum, all NExT applications will need to include the 5-page concept, references/citations, preliminary data*, NIH Biosketch, Intellectual Property statement, Current and Pending Support. Other documents (vide infra) should be provided as needed. NExT Applications will need to clearly indicate the specific requests and resource needs for the program’s success in both the Abstract (ProposalCentral) and the 5-page concept.

*Preliminary data is a requirement for the submission of a NExT application. If no preliminary data has been generated, please consider applying for a research grant or small business innovative research (SBIR) grant to generate the required data before applying to NExT.

Inclusion of Preliminary DATA

The best practices for the inclusion of preliminary data in NExT Applications includes rigor, minimization of bias, and transparency of reporting. Such factors are considered important criteria for the evaluation of the NExT application and contribute to a successful collaboration and ultimately development or a therapeutic. Several reporting guidelines have been applied in the scientific community and given the broad scope of drug discovery and development; no single set of criteria can apply to all studies.

For this reason, the NExT Program suggests that the applicants adopt the items listed in the following guideline while crafting their proposal, addressing the items that are appropriate, particularly those in bold font, when describing preliminary studies performed in support of their applications.

Experimental Design

Rationale for the selected models (animal and/or cell), clinical applications, and endpoints
Adequacy of experimental controls
Choice of route and schedule of intervention dosing
Justification for sample size, including statistical power calculation (discussion of effect of size in relation to potential clinical impact)
Appropriate statistical methods for analysis and interpretation of data
Authenticity of cell models via recent sequence analysis (such as short tandem repeat) to ensure that cell lines utilized in the described/anticipated studies are consistent with the original data in the repository

Minimizing Bias

Methods of blinding (allocation concealment and blinded assessment of outcome)
Strategies for randomization and/or stratification
Reporting data missing due to attrition or exclusion
Reporting all results (negative and positive)

Results

Independent validation and replication, if available
Relevant literature in support of/in disagreement with the results
Robustness and reproducibility of the observed results
Evidence of a dose (concentration) response relationship that is target dependent
Structures and synthetic routes for new molecular entities (NMEs)

NExT Application: Concept/Proposal

NExT Concept Application for Discovery, Development and Early Phase Trials of a single agent from the applicant’s institution/company/organization

The concept application document must not exceed 5 pages, and should outline the scientific nature and rationale of the proposed project and should include the following:

Background: Provide a summary of the field sufficient to allow an appropriate understanding of the scientific and medical context from which the opportunity emerges. Describe the target, targeted cellular pathways, and molecular mechanism of action, if known. Please be concise and specific; it is not necessary to address cancer incidence.
Hypothesis: Include a clear statement of the hypothesis(es) to be tested and define the objectives of the proposal. Specifically, address the scientific merit of your proposal by evaluating whether your hypothesis is supported by the field. Provide evidence to validate the target and/or the approach for pharmacological intervention based on in vitro, in vivo, or clinical studies from your research or the literature. Provide a summary of the key experiments you have conducted to date; manuscripts and supporting material can be uploaded as an appendix. Include an assessment of safety and therapeutic index. When available, include information on the competitive landscape and comparator efficacy studies.
Research Strategy and Specific Request(s) or Aim(s): Clearly describe the intended research strategy defining the specific activities requested from the NCI with the proposal; if the research activities necessary to move the concept forward to the clinic are not established or clear, please indicate this. Include specific details as necessary to demonstrate that the project has been well thought out (for example, if requesting assistance in the development of a pharmacodynamic assay, include a description of the analyte to be measured, strategy for biospecimen acquisition, assay platform, etc.). Address the feasibility of the proposed research strategy. For projects involving small molecules or natural products, please make sure to provide drug structural information.

Please also indicate whether you have had meetings with the FDA. Specify the expected resources from the NCI and the role of the applicant’s institute and collaborators in the project.
- Early-stage drug discovery projects, describe the proposed screening strategy, readiness of the primary assay, and any supporting secondary assays available, including structure-based, virtual, and selectivity assays. Supporting data can be uploaded as an appendix. For new molecular entities, describe the development status of the compound and optimization strategy. Indicate whether the compound has undergone medicinal chemistry optimization; if not, describe the proposed strategy. Describe available enzymatic, cell-based, and ADME assays, and where appropriate, access to a structure-based drug design platform; include a description of validated disease animal models (e.g., GEMMs). Specify the expected resources or expertise required from the NCI to facilitate advancement of the agent into first-in-human studies.
- For late-stage drug discovery projects, describe the current compound optimization status and strategy for further development (please refer to the NExT Stage Gates for guidance). Indicate whether the compound has undergone medicinal chemistry optimization. Indicate whether any formulation work has been performed or describe the proposed formulation strategy. Describe available PK/PD assays and clinical readiness of the assays. Include an evaluation of functional activity, potency, and PK/PD relationship, with an emphasis on therapeutic index if available; supporting data can be uploaded under the Preliminary and Supporting Data section.
- For clinical drug development projects of a single agent (Phase 0/I/II), provide a summary of all pertinent preclinical and clinical efficacy, toxicology, PK, and PD data, including studies of agent combinations (any additional information that cannot fit within the five-page concept document should be included in the Preliminary and Supporting Data Section). Describe the development plans for the agent, including the clinical trial design and objectives if known (e.g., primary and secondary study objectives, endpoints, patient population, eligibility criteria, estimated sample size, treatment arms/regimens, statistical endpoints, correlative studies, and patient samples required to perform correlative studies). For combination trials, include details about the originator of the agents (investigational/marketed) and rationale for conducting the study, indicating possible advantages over single agents/current therapies. If available, please upload the Investigator’s Brochure under the designated section.
Justification: Provide a statement to indicate whether your proposal adequately addresses unmet needs in oncology, including orphan or rare malignancies, pediatric cancers, “incurable” cancers, or cancers not commonly addressed by the pharmaceutical industry. Specify how the proposed compound or approach will advance clinical practice and improve current therapy. For imaging agents, provide an explanation of why the imaging represents a particularly innovative or promising approach to the prevention, detection, diagnosis, or treatment of cancer.
Uniqueness: Include a statement about how the proposed agent or therapy differs from standard therapies in practice or under clinical evaluation. If available, provide comparator efficacy and safety data for your investigational agent (biologic, vaccine, or new molecular entity) or cell therapy approach. Address the novelty of the concept with respect to the target and approach and indicate the likelihood of the concept advancing into the clinic without the assistance of the NExT Program.

NExT Application: Supporting Documents

References and citations (required): To optimize the limited space provided in the 5-page concepts, the NExT Program Application separates the citations and references that directly support the proposal content. Citations can be provided in any standard journal format (e.g. J. Med. Chem) with an optional link to the publication or PubMed reference.
One Key Publication (optional): If a publication or manuscript is available that provides significant support to the concept, this publication may be uploaded to this section. Only ONE publication is allowed for upload.
Preliminary and Supporting Data (required): Preliminary or supporting data that is key to the concept being described should be added to this section. In addition, figures, tables, etc may be referenced here to support the narrative in the 5-page proposal.
Intellectual Property (IP) Statement (required): The applicant should include a list of any patent references, issued or pending, with respect to either the agent or to any non-commercially available technology/material required for the development of the agent. If an application requires the use of non-commercially available technology/equipment that is patented by a third party, the applicant must provide documentation that the patent holder does not object to the applicant’s use with the proposed project.
Current and Pending Support (required): Please provide a list of current and pending funding sources. For applicants in academia, this would include current grants from both government and non-government sources, and any research resources provided directly from their institution. Individuals working directly for the government should provide an annual budget for their laboratory and any additional outside funding sources.
Principal Investigator Biosketch (required): The principal investigator biosketch should follow the NIH standard format. In the list of PI publications, please highlight any that are directly related to proposed project by preceding them with a double asterisk (**).
Additional Documentation (as appropriate): depending on the stage or specific request, additional information may be submitted, including a letter of commitment for any proposals containing a clinical component, Questionairre used for Biologic agent development, and the Investigator's Brochure for Clinical Trial collaborations.
- Clinical Letter of Commitment (required for IND-directed or GMP manufacturing proposals): All investigators requesting production of clinical-grade material and/or IND-directed toxicology studies must provide a letter of commitment from their institute. This letter is intended to ensure the reviewers and the NCI that the products and data produced by the NExT Program have a clinical outlet, and as such, the letter should indicate that the institution is committed to the filing of an IND and conduct of a clinical trial once NExT Program activities are completed. The letter of commitment should be signed by the head of the cancer center or the director of clinical research at the institution(s) at which the clinical trial will occur, or other party with obvious authority to commit the institution to conducting a clinical trial. If neither the signatory nor the applicant is a practicing medical oncologist, the letter of commitment should also contain the signature and contact information of the clinician who will be the principal investigator of the clinical trial. It may also be helpful for the applicant to include a supplemental letter from this clinician indicating that he or she is willing to undertake the trial.
- Questionnaire for Biologics (required for Biologics agents): If submitting a project involving the late discovery or development of biologic agents, please complete the NCI Biological Resources Branch (BRB) Questionnaire.
- Investigational Brochure (required for clinical): For clinical trial collaborations with CTEP, please upload an Investigator's Brochure (IB) that is related to the agent described in the proposal.