DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

The Clinical Development Award: Accelerating Ovarian Cancer Research into Clinical Application

Posted September 14, 2017

The Clinical Development Award (CDA) is a funding opportunity within the Ovarian Cancer Research Program (OCRP) portfolio that provides support for the translation of promising preclinical findings into products for clinical applications. Introduced in fiscal year 2016 (FY16), the OCRP funded four CDA applications that demonstrated near-term clinical impact and a feasible plan to transition to the next stages of development after completion of the award. These projects seek to improve the outcomes of ovarian cancer patients through the development of new diagnostic techniques, drugs, and treatment options.

Dr. Fiona Simpkins at the University of Pennsylvania proposes to use positron emission tomography (PET) imaging to non-invasively identify patients who will benefit from DNA-damaging anti-cancer therapies (OC160269). Dr. Simpkin’s research team has developed a novel PET radiotracer to quantitatively image active PARP-1, a marker of the DNA damage response in cells. In this proposal, she will validate the technology for use in patients and track the levels of PARP-1 in cancer cells before, during, and after chemotherapy treatment. By using this tracer to measure PARP-1 in ovarian cancer patients throughout the course of their disease, Dr. Simpkins aims to establish PARP-1 as a biomarker and predictive tool to identify how patients will respond to different types of treatment and prevent unnecessary exposure to toxic agents if there will be no benefit.

Dr. Daniela Matei at Northwestern University proposes to combine two cutting-edge areas of cancer research – immunotherapy and epigenetics – to improve treatment options for women with chemotherapy-resistant ovarian cancer (OC160260). In this study, Dr. Matei will test the effect of a novel DNA methylation inhibitor, guadecitabine, on making ovarian cancer cells more recognizable to the immune system. Additionally, she will assess the ability of this new treatment to enhance the efficacy of the PD-1 targeted antibody used in immunotherapy, pembrolizumab, which would offer ovarian cancer patients alternative treatment options beyond traditional chemotherapy.

Dr. Elizabeth Swisher at the University of Washington proposes to use whole genome sequencing to develop a diagnostic tool to better predict patient responses to ovarian cancer drug treatment (OC160274). In this study, Dr. Swisher will examine the DNA of tumor samples collected in the ARIEL2 clinical trial to identify signatures of genetic mutations that predict response to the PARP inhibitor rucaparib. PARP inhibitors have shown clear efficacy against cancers with mutations in the BRCA1 and BRCA2 genes, but have less predictable outcomes in other types of ovarian cancer. If successful, the mutator signatures characterized by Dr. Swisher could be used as biomarkers to identify a new population of ovarian cancer patients who will respond well to rucaparib, despite lacking BRCA mutations.

Dr. Michael Birrer at the University of Alabama at Birmingham proposes to develop a novel therapeutic strategy that targets the metabolism of cancer cells for treatment of ovarian cancer (OC160463). In this study, Dr. Birrer will test the efficacy of a glutaminase-1 enzyme inhibitor, CB-839, in reducing ovarian cancer growth as a solitary treatment or in combination with the PARP inhibitor olaparib. Based on pre-clinical data, he expects that inhibiting the cell’s use of glutamine with CB-839 treatment will starve them of a key nutrient, as well as induce DNA damage that can be targeted by other drugs. If successful, Dr. Birrer’s study will exploit a new molecular pathway to provide ovarian cancer patients with alternative treatment options.

Based on the exciting research funded in FY16, the OCRP has once again offered the CDA funding opportunity in FY17. A new addition to the award this year is an option for Principal Investigators who are proposing clinical trials to collaborate with an Early-Career Investigator. With this option, the OCRP aims to encourage the next generation of ovarian cancer researchers to become involved in and conduct clinical trial research. The FY17 application and review process is underway, and the OCRP looks forward to continuing its mission to accelerate the clinical introduction of medical products and technologies that target ovarian cancer and improve the lives and outcomes for ovarian cancer patients.

OCRPClinicalDevelopmentAwardFigure.jpg

Links:

Public and Technical Abstracts: Epigenomic Priming as an Immunotherapy Enhancer in Ovarian Cancer

Public and Technical Abstracts: Investigation of a Novel PARP Inhibitor PET Tracer in Ovarian Carcinoma

Public and Technical Abstracts: Mutator Phenotypes that Better Predict PARP Inhibitor Response in Ovarian Carcinomas

Public and Technical Abstracts: Treatment of Recurrent, Platinum-Resistant Ovarian Cancer with Glutaminase 1 and PARP Inhibitors

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Last updated Thursday, September 14, 2017