A response to CA-125 has occurred if there is at least a 50% decrease from baseline: 1. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Complete response (CR) is disappearance of all target lesions. The endpoint of ORR defined as the percentage of patients with a best response of CR or PR using RECIST v 1.1 or a response per Gynecologic Cancer InterGroup cancer antigen 125 (GCIG CA-125) criteria. PART 2 (completed enrollment): Evaluation of HRD status and rucaparib efficacy in patients who received at least 3 prior chemotherapy regimens PART 1 (completed enrollment): Evaluation of HRD status and rucaparib efficacy in patients who received в‰Ґ1 prior platinum-based regimen and had platinum-sensitive disease This Phase 2 study (ARIEL2) will also compare archival versus recently collected tumor tissue in order to validate the use of archival tumor tissue for assessment of HRD status in ARIEе…ѓ. Once determined, this signature will be prospectively applied to ARIEL2 PART 2 and ARIEе…ѓ. One of the main advantages of detecting tumor genomic LOH is that it can identify HRD tumors regardless of the underlying mechanisms, which include both known (i.e., BRCA mutations) and unknown genetic and other mechanisms. Genomic scarring can be assessed by quantifying the extent of loss of heterozygosity across the tumor genome (tumor genomic LOH). The HRD signature will be based on an association between the extent of genomic scarring (a downstream consequence of HRD) in a patient's tumor and observed clinical benefit from rucaparib treatment. This study will define a molecular signature of HRD in ovarian cancer that correlates with response to rucaparib and enables selection of appropriate ovarian cancer patients for treatment with rucaparib. Rucaparib is currently being investigated as monotherapy in patients with cancer associated with breast cancer susceptibility gene 1 (BRCA1) or BRCA2 mutations.Д¬linical data with PARP inhibitors indicate there is an ovarian cancer patient population beyond just those with germline BRCA (gBRCA) mutations that may benefit from treatment with a PARP inhibitor. An oral formulation is the focus of current development efforts. The safety and efficacy of rucaparib has been evaluated in several Phase 1 and Phase 2 studies. Rucaparib is an orally available, small molecule inhibitor of poly-adenosine diphosphate ribose polymerase (PARP) being developed for treatment of ovarian cancer associated with homologous recombination (HR) DNA repair deficiency (HRD). Why Should I Register and Submit Results?.

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