Attach_1_or_4_Background_Intro.pdf

PREVENT CANCER PRECLINICAL DRUG DEVELOPMENT PROGRAM

BACKGROUND AND INTRODUCTION

RFP NO. N01CN77019-18

The Division of Cancer Prevention (DCP) is a principal Division of the National Cancer Institute (NCI) devoted to cancer prevention research. Research supported by the DCP encompasses a continuum of preclinical and clinical studies, including a better understanding and elucidation of cancer initiation processes, methods of identifying individuals at risk for cancers, and the development of early cancer detection methodologies and cancer preventive interventions, with the overarching goal to prevent invasive cancer and associated deaths in human subjects. The PREVENT Cancer Preclinical Drug Development Program (PREVENT;

http://prevention.cancer.gov/major-programs/prevent-cancer-preclinical) was formally launched by the DCP in 2011 as a contract-based program with its primary mission to advance the preclinical development of cancer-preventive interventions and intermediate biomarkers, and to support/enable their clinical translation. The PREVENT Program accepts concept applications from academia, government, small businesses, and the pharmaceutical industry, and selects meritorious projects through peer review and organizational prioritization processes. Approved projects are entered into the appropriate stage of the PREVENT pipeline, which is supported by NCI contract resources, and implemented in a milestone-driven manner from early proof of concept studies to secondary testing, and the final steps of Investigational New Drug (IND) applications-enabling studies. Since its inception, the PREVENT Program has partnered with researchers in the extramural community and supported over 74 projects, for which 73 Task Orders were awarded to two separate pools of competitively selected prime contract holders with requisite technical capabilities in the areas of (1) in vivo development/animal efficacy/biomarker development, and (2) toxicology/pharmacology testing. One clinical trial has been initiated on a PREVENT-supported cancer vaccine, while INDs are expected to be filed for five other PREVENT-supported projects.

The PREVENT Program’s current scientific focus areas include cancer immunoprevention (e.g.

vaccines), anti-inflammatory approaches, molecularly targeted chemoprevention agents, drug repurposing, and toxicity reduction strategies. Because successful cancer prevention requires long term (possibly life-long) use of preventive agents in healthy subjects, a rigorous preclinical development path must be followed for any lead intervention development projects not only to establish and confirm their preventive efficacy profiles, but also to demonstrate safety in pertinent nonclinical models, thereby attaining the highest achievable benefit/risk ratio before they can progress to clinical trials.

Cancer preventive vaccines have the potential to provide long-lasting protective immunity virtually in the absence of long-term toxicity concerns. Recent advances in tumor immunology and anticancer immunotherapies have uncovered the host immune system’s capacity to mount effective antitumor immune responses to tumor-specific or tumor-associated antigens and counter cancer growth. When tumor-derived immune suppression is blocked by immune checkpoint inhibitors in the established tumor immune microenvironment, the immune system can exert more robust antitumor immune responses. It is highly conceivable that cancer vaccines targeting certain immunogenic tumor-associated antigens may induce more effective antitumor immunity if given before or early in the tumorigenic process, and thus may prevent or deter the development of malignant lesions.

The development and introduction of cancer immunopreventive agents, such as vaccines, remain one of the highest priorities for the PREVENT Program. As the PREVENT project portfolio matures, multiple immunoprevention projects are expected to progress to the late stage of preclinical development, which will necessitate the supply of clinical-grade vaccines and other immunomodulatory agents in support of IND-enabling studies. To meet the anticipated technical needs in the PREVENT pipeline, the NCI has a requirement for product development-oriented services, related to clinical-grade product development and manufacturing support, for promising biopharmaceutical agents identified through the PREVENT Program. The agent production services will encompass activities commonly associated with the development of biopharmaceutical products that are required for IND and/or Biologic License Applications (BLAs). These services will be made available for candidate immunopreventive agents arising from academia, the private sector, or other sources that are selected through the PREVENT pipeline’s agent development processes as described above. The early and rapid identification of subjects at risk for cancers is highly critical to successful implementation of effective cancer preventive interventions and risk management. Based on emerging data and newer evidence, the development and production of diagnostic reagents or specific assay methodologies may become necessary in the ensuing years. For that purpose, this third component includes services supportive of new methodologies for early cancer detection and high-risk cohort identification.

Along with the existing components that support in vivo efficacy testing and biomarker development as well as toxicology and pharmacology testing, it will enhance the capability and capacity of the PREVENT Program to support the development of biopharmaceutical products, in direct support of the mission of the Division of Cancer Prevention, which is to prevent invasive cancer and associated deaths.

The purpose of this solicitation is to procure Research & Development services to support the PREVENT Program in the areas of (1) in vivo development/animal efficacy/biomarker development, (2) preclinical product development and CGMP manufacturing of biopharmaceutical agents, and (3) toxicology/pharmacology testing. In order to meet the demands for all services in a timely and proactive manner, the NCI intends to award contracts that provide a suite of technical task support services, using the Indefinite Delivery-Indefinite Quantity (IDIQ) contract mechanism. Under the IDIQ mechanism, the NCI will award Task Orders for specific activities that meet technical requirements tailored for each identified PREVENT project’s needs. While the overall suite of services listed is comprehensive, the intent is to provide individual services on a case-by-case basis for a diverse collection of candidate agents, rather than carry a single candidate product through an entire preclinical development pathway. These services are intended to help investigators in various scientific disciplines obtain critical data needed to advance their agents further through the PREVENT pipeline, acquire additional funding from other sources, gain prospective partnerships (either for further development or to support Phase I trials), fulfill regulatory requirements, and/or complete studies needed to apply for an IND and enter a Phase I trial.