Objectives In the US and EU, rucaparib is approved for recurrent ovarian cancer (rOC) associated with or without homologous recombination deficiency (HRD; ie, BRCA mutation or high genomic loss of heterozygosity [LOH]); nivolumab is approved for recurrent, locally advanced/metastatic UC. Preclinical data suggest that PARP inhibition may work synergistically with PD-L1 blockade by stimulating the tumor microenvironment to enhance immune-mediated antitumor activity. ARIES (NCT03824704) is evaluating rucaparib plus nivolumab for rOC (Cohorts A1/A2) or locally advanced, unresectable/metastatic UC (Cohort B).
Methods Cohort A is enrolling 2 groups of patients (A1 and A2) with platinum-sensitive rOC who have received ≤2 prior treatments. The first group (Cohort A1) includes wild-type BRCA and high genomic LOH (≥16%) rOC; the second exploratory group (Cohort A2) includes BRCA-mutated rOC. Cohort B is enrolling UC patients regardless of HRD or PD-L1 status who are cisplatin-ineligible and declined carboplatin-based therapy or progressed following 1 line of platinum-based therapy. Patients in Cohorts A1 and B must have measurable disease (RECIST v1.1). Tumor sample is mandatory for tumor BRCA/LOH status assessment. Prior PARP or immune checkpoint inhibitor treatment is exclusionary. Patients are receiving rucaparib (600 mg PO BID) and nivolumab (480 mg IV Q4W). The primary endpoints are investigator-assessed objective response rate (RECIST v1.1; Cohorts A1 and B) and the effect of rucaparib on the immune microenvironment (Cohort A2).
Results Approximately 140 patients are being enrolled in the US.
Conclusions ARIES is assessing the efficacy of rucaparib plus nivolumab in patients with rOC or locally advanced, unresectable/metastatic UC.
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