A randomized, phase II trial to evaluate the safety and efficacy of eribulin mesylate in combination with atezolizumab compared to atezolizumab alone in subjects with locally advanced or metastatic transitional cell urothelial cancer where cisplatin-based treatment is not an option

BackgroundPatients with advanced urothelial carcinoma are often not candidates for cisplatin-based therapies. This study explored the efficacy and safety of atezolizumab and eribulin compared to atezolizumab alone in this population.MethodsEligible patients had advanced disease that was treatment-naïve in cisplatin-ineligible patients or occurring during or within 12 months of platinum use, and were randomized in a 2:1 ratio to receive eribulin 1.4mg/m2 on days 1 & 8 with atezolizumab 1200mg/m2 on day 1 (A+E) or atezolizumab monotherapy on day 1 (A) in 21 day cycles. Patients were evaluable if ≧ one dose of assigned treatment was received. Planned enrollment was for 66 patients. The primary outcome measure was objective response rate (ORR), where a 1-sided p-value < 0.10 would favor A+E as having a significantly increased response rate.ResultsThe Phase 2 study enrolled 33 evaluable patients. Median age at enrollment was 73 years. The median number of cycles received was 4 in A and 3 in A+E. Of the 23 A+E patients, 11 were responders, with an objective response rate (ORR) of 47.8%. There were 2 responders amongst the 10 A patients (ORR 20.0%, p= 0.132). There were five deaths on A, all due to disease progression [PD]; and 10 on arm A+E, 7 from PD (cause not reported for 3). Five patients currently remain on treatment for a median of 8 cycles. The rates of adverse events were similar between arms, including grade 3 or higher hematologic toxicity and creatinine elevation and neuropathy of any grade. Table: 1993P Patient characteristics A A+E Total Median Age (years) 75.5 73.0 73.0 Males (%) 8 (80.0) 17 (73.9) 25 (75.8) Females (%) 2 (20.0) 6 (26.1) 8 (24.2) Prior platinum 6 (60.0) 10 (43.5) 16 (48.5) No prior platinum 4 (40.0) 13 (56.5) 17 (52.5) Prior therapies Surgery Only 3 (30.0) 4 (17.4) 7 (21.2) No Prior Platinum 1 (10.0) 9 (39.1) 10 (45.5) Prior Platinum 6 (60.0) 10 (43.5) 16 (48.5) ConclusionsA+E demonstrated clinical activity, however, the study was terminated administratively prior to target enrollment due to changes in standard of care due to the FDA approval of enfortumab vedotin and pembrolizumab (EV+P). Further studies combining eribulin and checkpoint inhibitors may focus on patients who cannot tolerate EV.Clinical trial identificationNCT03237780.Legal entity responsible for the studyNational Cancer Institute.FundingNational Cancer Institute.DisclosureM. Krailo: Financial Interests, Personal, Advisory Board, Receives compensation for DSMC membership: Merck, Sharpe, and Dohme. D.I. Quinn: Financial Interests, Personal, Advisory Board, Advisory Board; Phase 3 trial leadership: Merck; Financial Interests, Personal, Advisory Board, Advisory Board: Seattle Genetics; Financial Interests, Personal, Invited Speaker, Educational lectures and Advisory Board: Pfizer; Financial Interests, Personal, Other, Phase 3 trial leadership: Bayer; Financial Interests, Personal, Full or part-time Employment, Senior Medical Director: AbbVie; Financial Interests, Personal, Stocks/Shares, Stock as part of job payment: AbbVie; Financial Interests, Institutional, Steering Committee Member, phase 2 study, phase 3 study: Pfizer; Financial Interests, Institutional, Funding, phase 2 study: Merck; Financial Interests, Personal and Institutional, Coordinating PI, Coordination of international phase 2/3 trial: Bayer. All other authors have declared no conflicts of interest.