ATLAS: A phase II open-label study of rucaparib in patients with locally advanced or metastatic urothelial carcinoma (mUC).

Abstract

TPS496 Background: There are currently no standard treatment options for patients with mUC that has progressed on or after platinum (cisplatin/carboplatin)–based chemotherapy (PBC) and/or immune checkpoint inhibitors (ICIs), emphasizing the need for new therapies. Analysis of The Cancer Genome Atlas bladder cancer dataset suggests that approximately 60% of bladder cancer tumors have homologous recombination deficiency (HRD), as defined by high genomic loss of heterozygosity (LOH) or a deleterious mutation in a homologous recombination pathway gene. The poly(ADP-ribose) polymerase inhibitor (PARPi) rucaparib has demonstrated activity in tumors with HRD and in homologous recombination proficient tumors in the recurrent ovarian cancer setting. The ATLAS (NCT03397394) trial will evaluate the efficacy and safety of rucaparib in patients with locally advanced/unresectable UC or mUC treated with 1–2 prior anticancer treatments. Methods: Eligible patients must have measurable disease per RECIST v1.1, adequate organ function, and radiographic progression after 1–2 prior regimens (eg, PBC and/or ICI). Confirmation of HRD status before enrollment is not required, but fresh tumor tissue or recently obtained archival tissue is mandatory for HRD profiling. Prior PARPi treatment is exclusionary. All patients will receive oral rucaparib 600 mg BID until disease progression or other reason for discontinuation. The coprimary endpoints are confirmed objective response rate (investigator-assessed per RECIST v1.1) in the intent-to-treat and HRD-positive (signature based on tumor genomic LOH) populations. Secondary endpoints include response duration, progression-free survival, overall survival, safety, and pharmacokinetics. Exploratory endpoints include evaluation of molecular biomarkers associated with response and resistance to rucaparib, including changes in plasma and tumor samples, and circulating tumor DNA. Patients are being enrolled in 6 countries (France, Germany, Italy, Spain, UK, and USA), with a target enrollment of 200 patients. The study has > 90% power to reject the null hypothesis (P = 0.10) at a 5% significance level if the true response rate for rucaparib is 20%. Clinical trial information: NCT03397394.