We verified that the SEOC GDA models respond to cisplatin or olaparib similarly to patients. olaparib is efficacious only for BRCA deficient tumors and cisplatin is optimally effective in these tumors. The combination of these two drugs for BRCA deficient tumors is no more efficacious than cisplatin alone. We have evaluated consolidated therapy for BRCA1-deficient GDA tumors in which mice are treated with cisplatin to de-bulk tumors followed by treatment with an FDA-approved drug shown in drug library screens to be effective at killing both human and mouse SEOC derived cells in 2-D culture. With standard routes of introduction, the compound was not more effective than the vehicle control. We are now evaluating the efficacy of this drug when delivered by implanted continuous dosing pumps. Studies for all other objectives are currently in progress. We have also entered in a CRADA-supported collaboration with a Big Pharma company to assess the biomarker environment and conduct efficacy studies with combined treatment regimen of a PARP inhibitor, a VEGFR inhibitor, and an immune checkpoint inhibitor. These efficacy tests will be performed in both BRCA-proficient and BRCA-deficient models.
