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Companion Diagnostics for Cancer Immunotherapies

The field of cancer immunotherapy has expanded rapidly over the last few years with the development of several new immunomodulatory agents that have shown promising clinical results.  As one example, in 2011, the FDA approved a therapeutic antibody for the treatment of melanoma, ipilimumab (YERVOY?), which blocks cytotoxic T-lymphocyte antigen 4 (CTLA-4), a receptor found on T-cells that downregulates the immune system.  In 2014, the FDA approved another agent for the treatment of melanoma, pembrolizumab (KEYTRYDA?), which is the first approved therapeutic antibody targeting the programmed cell death protein 1 (PD-1), another T-cell receptor that plays a role in immune inhibition.  These two therapeutic antibodies are representative of a major class of cancer immunotherapies known as immune checkpoint inhibitors, and several other therapeutic agents are currently in development targeting CTLA-4, PD-1, and other immune checkpoint proteins.  Other major classes of cancer immunotherapies currently being developed include therapeutic cancer vaccines, as well as therapeutic approaches that involve ex vivo manipulation and engineering of immune cells, including chimeric antigen receptor (CAR) therapy.
Cancer immunotherapies offer several advantages over current standard-of-care cancer treatments, including the potential to eradicate cancer cells not visible to the surgeon, as well as disseminated metastases that remain undetectable using current imaging modalities.  Immunotherapy approaches may also prove effective at targeting slowly dividing or quiescent tumor cells that do not respond well to chemotherapy and/or radiation, and certain immunotherapy approaches are expected to suppress re-emergence of the cancer (following initial treatment) by exploiting the immune system?s memory.  In fact, early results have shown positive and dramatic clinical outcomes for some of the more recent cancer immunotherapies, even in patients with advanced disease; however, it is often the case that only a subset of patients respond to such therapies for reasons that are often poorly understood. 
As the field of cancer immunotherapy continues to evolve, and as more cancer immunotherapies advance through clinical development, there will be an increasing need for companion diagnostic assays capable of predicting responders (and non-responders) to cancer immunotherapies.  Moreover, such assays will become critically important as these therapies are eventually utilized as part of routine clinical practice.
Program Goals
The goal of this contract topic is to develop companion diagnostic assays and technologies capable of identifying individual patients for whom a particular cancer immunotherapy regimen will be safe and effective.  This includes cancer immunotherapies that have already received marketing approval from the FDA, as well as cancer immunotherapies currently in clinical development.  This topic is specifically intended to address cancer immunotherapies that depend upon eliciting an immune response.  Projects that do not meet this requirement will not be considered responsive.  For example, a monoclonal therapeutic antibody that exerts a direct antitumoral effect either by neutralizing the antigen or by activating signaling pathways within the target tumor cell, but does not elicit an immune response for its clinical activity, is not considered an immunotherapy and would not be considered responsive.
The goal of this contract topic is NOT to solicit any particular technology or approach, i.e., this contract topic is technology agnostic.  Technologies employed may include, but are not limited to, genetic analysis, other molecular diagnostic approaches, cell culture and cell expansion technologies, imaging modalities, radio-labeling approaches, and data science/analytics.  This contract topic is specifically intended to support the development of assays that provide predictive and/or prognostic information for a specific cancer immunotherapy.  Projects that do not meet this requirement will not be considered responsive.  For example, development of an assay for the sole purpose of measuring whether an agent modulates its intended molecular target (e.g., pharmacodynamic assay) would not be considered responsive.  Likewise, development of an assay for providing information that is useful in cancer diagnostics or prognostics but not in determining the safe and effective use of a therapeutic product/regimen would also not be considered responsive.  Noninvasive and minimally invasive sampling methods (e.g., body fluids and mouth swab) are preferred.  Other sampling methods are acceptable if they provide significantly improved predictive value, accuracy, and clinical applicability.
Phase I Activities and Expected Deliverables

Develop a working companion diagnostic test for a specific cancer immunotherapy regimen, which meets the criteria described above
Characterize the variation, reproducibility, and accuracy of the test, and implement a QA/QC plan
Demonstrate suitability of the test for use in the clinic, and conduct benchmarking studies against current tests (if available); algorithms must be tested with datasets other than those used for their development
In cases where a companion diagnostic test is proposed for a specific immunotherapeutic that is not yet commercially available (i.e., approved for marketing), the applicant must provide proof of collaboration or partnership with the entity that is developing the therapeutic agent or with an established diagnostic company
All offerors must establish a collaboration or partnership with a diagnostic and/or pharmaceutical company and/or clinical/research institution that can provide relevant clinical trial specimens; offerors must provide a letter of support from the partnering organization in the Phase II application
Deliver the SOP of the working test to NCI for evaluation

Phase II Activities and Expected Deliverables

Incorporate the assay into a standard kit for clinical testing and eventual distribution and sale
Demonstrate clinical utility and value by testing sufficient numbers of patients from multiple sites to unequivocally demonstrate statistical significance with regard to patient selection for the therapy
If the primary conclusions reached during the Phase I studies were based on animal experiments or ex vivo modeling, then a correlation study between these models and treatment in human subjects is expected
Establish marketing partnership or alliance with the company developing the therapy, unless the therapy is already approved for marketing
It is preferred that the test be performed in at least one independent CLIA-certified laboratory
Deliver the final SOP to NCI for evaluation

National Center for Advancing Translational Sciences (NCATS)
The mission of the National Center for Advancing Translational Sciences is to catalyze the generation of innovative methods and technologies that will enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions.  For additional information, please visit our home page at
It is strongly suggested that potential offerors not exceed the total costs (direct costs, facilities and administrative (F&A)/indirect costs, and fee) listed under each topic area.

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