Description:
The demand for companion diagnostics has greatly increased with the recognition that matching the right patient to the right drug at the right time can improve patient care and may decrease health care costs. More than a dozen companion diagnostic tests have been approved by the FDA to guide the prescription of products in oncology, cardiovascular disease, and infectious disease. Among them, tests of the Philadelphia chromosome, tumor-associated EGFR overexpression, and HER2 protein overexpression have been identified by the FDA as “required” for the identification of candidate cancer patients to receive Gleevec, Erbitux (cetuximab), and Herceptin (trastuzumab), respectively, for certain indications. In 2011, the FDA approved two pairs of new oncology drugs and their companion diagnostic tests simultaneously. These decisions suggest that the era of companion diagnostics has arrived.
Despite initial success, many therapies in the cancer arena (both primary and adjuvant treatments) still lack prediction and guidance from companion diagnostics. Many patients die from recurrence and metastasis as a result of unpredicted resistance to drugs or radiation developed during therapy, or due to pre-existing tumor insensitivity to the drugs or radiation therapy. Guidance towards effective and safe therapy is greatly needed and can be provided by companion diagnostics, which include tests developed after a drug has come to market, tests developed in conjunction with the development of a therapeutic agent, and tests to predict the interaction of novel agents with existing standard of care therapies, such as radiation or cytotoxic chemotherapy. This topic seeks to stimulate research, development, and commercialization of innovative tests and technology platforms for all types of companion diagnostic applications. Companies with advanced biomarkers are particularly encouraged to apply.
Project Goals
The goal of this contract topic is to develop companion diagnostic assays that identify patients for which a particular therapeutic regimen, including radiation therapy, existing drugs, and drugs in clinical development will be safe and effective.
Tests for monitoring the response to treatment for the purpose of adjusting treatment (e.g., schedule, dose, discontinuation) to achieve improved safety or effectiveness are also acceptable under this contract topic. Though the examples mentioned above are for targeted therapies, tests may also encompass therapeutics outside of this class. These tests include, but are not limited to, tumor RNA/protein expression or overexpression, gene mutation or deletion/insertion, allelic variation, and enzymatic deficiency. Noninvasive and minimally invasive sampling methods (e.g., body fluids and mouth swab) are preferred. Other sampling methods are also acceptable if they provide significantly improved predictive value, accuracy, and clinical applicability.
This topic is not intended to support the development of assays that do not provide predictive/prognostic information for a therapy. For example, the development of an assay for the sole purpose of measuring whether the drug hits its intended target (e.g., pharmacodynamic assay) would not be considered responsive under this contract topic. A novel test/device providing information that is useful in cancer diagnostics or prognostics, but not a determining factor for the safe and effective use of a therapeutic product, would also not be considered responsive.
Phase I Activities and Expected Deliverables
• Develop a working companion diagnostic test that meets the criteria described above
• Characterize the variation, reproducibility, and accuracy of the test, and implement a QA/QC plan
• Demonstrate the 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 the drug for which the companion diagnostic test being developed 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
• Demonstrate clinical utility and value by testing sufficient numbers of patients from multiple sites to unequivocally prove statistical significance with regards 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
