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NIH/NCI 467 - Development of Cancer Immunoprevention Agents

Fast-Track proposals will be accepted.

Direct-to-Phase II proposals will be accepted.

Number of anticipated awards: 2-4

Budget (total costs, per award):

Phase I: up to $400,000 for up to 12 months

Phase II: up to $2,250,000 for up to 2 years

PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED.

 

Summary

While therapeutic cancer vaccines and immunomodulatory drugs have been actively developed for many cancer indications, there is a significant unmet medical need to develop such agents for cancer prevention and interception. Effective prophylactic vaccines are available for virus-induced cancers (e.g., human papillomavirus (HPV) vaccines and Hepatitis B vaccines that reduce the incidence of cervical and liver cancers respectively). However, most cancers are not caused by viruses. There are specific high-risk human populations that have predictable and measurable risks of developing certain cancers (i.e., individuals with high-penetrance germline mutations, individuals diagnosed with precancers, or individuals exposed to environmental carcinogens). These populations would greatly benefit from the development of specific vaccinations or immunomodulatory drugs.

Ongoing research on the role of immune mechanisms during tumor initiation and progression is rapidly evolving. Recent proof-of-principle preclinical studies have demonstrated that vaccines and other immunological interventions can induce host immune responses and provide immunoprevention efficacy by controlling tumor onset and progression in animal models of several cancers. These studies suggest that immunoprevention could be effectively translated to the clinic. Since most immunopreventive strategies aimed against non-viral cancers currently are at the preclinical or early clinical research stages, there is a need to stimulate small business development and commercialization of these products.

Project Goals

The goal of this solicitation is to develop efficacious immunopreventive strategies for cancer prevention and interception for high-risk cohorts by leveraging the existing knowledge and understanding of the complex immune pathways at the early stages of tumor development to further evaluate efficacy and understand mechanisms of action of the immunopreventive agent and its side effects. This initiative is to encourage the development and commercialization of novel innovative
vaccines and immunomodulatory drugs for cancer prevention and interception in high-risk cohorts, including but not limited to:

  • Individuals with high-penetrance germline mutations, heritable cancer syndromes (HCS)
  • Individuals diagnosed with precancers (adenoma, carcinoma in-situ, dysplasia, pancreatic intraepithelial neoplasia (PanIN), intrapapillary mucinous neoplasm (IPMN), serous tubal intraepithelial carcinoma (STIC), prostatic intraepithelial neoplasia (PIN), cervical intraepithelial neoplasia (CIN), Barret’s esophagus, etc.)
  • Individuals exposed to environmental carcinogens (smokers, firefighters, individuals exposed to asbestos, etc.)
  • Special populations (e.g., Monoclonal gammopathy of undetermined significance (MGUS))
  • Cancer survivorship cohorts (second primary cancers)

The activities responsive under this SBIR topic include the development of immunopreventive vaccines or immunomodulatory drugs for high-risk cohorts based on an identified early immune pathway(s) or target(s) involved during tumorigenesis. The vaccines can be single or multi-agent (peptide, DNA- or mRNA-based) and could also be combined with
other immunomodulatory drugs for increased efficacies. These vaccines could be prophylactic (prevents cancer initiation) or interception vaccines (inhibits precancer progression to cancer).

Activities not responsive to this announcement:

Development of immunotherapy; development of agents to prevent cancer recurrence or metastasis; proposals without initial preliminary prevention or interception efficacy data in relevant prevention models.


Phase I Activities and Deliverables:

Offerors should have identified a lead immunopreventive vaccine or immunomodulatory drug with supporting in vitro and preliminary in vivo efficacy data in relevant models. Phase I activities should generate scientific data confirming the clinical potential of the proposed immunopreventive vaccines or immunomodulatory drugs. The Phase I research plan must contain specific, quantifiable, and testable feasibility milestones. Depending on the development stage of the agent, examples of activities and deliverables include but are not limited to:

  • Preclinical in vivo efficacy, safety, PK/PD, and toxicity evaluation (non-GLP) studies in appropriate animal models:
    • Assess the immunogenicity and antitumor efficacy of immunopreventive vaccines or immunomodulatory drugs in an immunocompetent transgenic or carcinogen-induced animal model representing high-risk cohorts. The proposed model shall recapitulate molecular and histopathological aspects of human tumorigenesis with a range ofhistological changes progressing from pre-malignant lesions to full-scale malignant tumors with high penetrance.
    • Determine the planned dose, schedule, and delivery method. Determine the scheduling strategies to prevent (cancer initiation) or target (intercept) pre-invasive lesion formation and progression along with the rationale for the suitability of treatment initiation (i.e., early vs. delayed intervention) and termination time points.
  • Determine the antitumor efficacy endpoints such as tumor incidence, multiplicity, burden, and survival as well as histopathological analysis of tumor grade and stage upon the termination of the experiment. Examine signs of agentassociated complications and assess toxicity and potential side effects.
  • Present Phase I results and future development plan to NCI staff.

Phase II Activities and Deliverables:

Phase II activities should support the commercialization of the technology, including but not limited to the following activities:

  • Perform IND-enabling studies as appropriate for the agent under development:
    • Dose range-finding or maximum tolerated dose studies in relevant animal species.
    • GLP toxicological and pharmacological studies.
    • Demonstrate scalability and manufacturing of GLP or GMP-grade material.
  • Develop and execute an appropriate regulatory strategy (e.g., INTERACT meeting and/or pre-IND meeting).
  • Development and validation of biochemical assays required for clinical trials (e.g., pharmacokinetic, pharmacodynamic, and/or immunogenicity assays).
  • Establish a clinical study plan/strategy and submit an IND application for FDA approval to initiate a first-in-human clinical trial.
  • For agents with an already FDA-approved IND, offerors may:
    • Propose manufacturing of GLP or GMP-grade material.
    • Conduct an immunoprevention clinical trial.
  • Present Phase II findings to NCI program staff.

 

Receipt date: Friday, October 18, 2024, 5:00 p.m. ET

Apply for this topic on the Contract Proposal Submission (eCPS) website.

View the full PHS2025-1 Contract Solicitation.

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