AURORA: A single arm, multicentre, phase II clinical trial of atezolizumab immunotherapy for advanced squamous cell carcinoma of the bladder and urinary tract.

4608 Background: Urinary tract squamous cell carcinoma (UTSCC) is a rare disease, comprising approximately 3% of histological subtypes from the bladder and urinary tract. Limited data exist to support treatment choices and no prospective trials, dedicated specifically to this histology, have been undertaken to evaluate immunotherapy. Prior data indicate high PD-L1 expression and tumour immune cell infiltration in a proportion of UTSCC cases. We report the Stage 1 outcome for the AURORA clinical trial, which tested atezolizumab immunotherapy for patients with incurable UTSCC. Methods: Patients had progressive, measurable, UTSCC and ECOG performance status 0-2. Mixed histology was permitted but with no urothelial carcinoma component. One prior line of systemic chemotherapy was permitted for advanced disease but no prior immunotherapy. Treatment comprised atezolizumab (1680 mg IV, q28d) until disease progression and for up to one year if tolerated. The primary endpoint was best overall objective response rate (ORR; RECIST v1.1) with a Simon 2 stage statistical design, and planned, independent, interim efficacy review after 19 patients were assessable for response (without a recruitment pause). If ≥4 of the first 19 patients (Stage 1) achieved an objective response (confirmed partial or complete response), then recruitment would continue through Stage 2, where ≥8 responses in 33 patients were required to indicate further investigation was warranted (p1 = 15%, p2 = 35%, 1-sided alpha = 0.1, power = 90%). Secondary endpoints included progression free survival (PFS), overall survival (OS), duration of response, safety and tolerability (CTCAEv5). Results: 3 of the first 19 recruited patients achieved an objective response (15.8%, 95% confidence interval (CI) 3.4 - 39.6; 3 partial and no complete responses) leading the Independent Data Monitoring Committee to recommend closure to recruitment. 3 further patients (15.8%) achieved a best response of stable disease. With a median duration of follow up of 10.1 months (95% CI 3.5 - not calculated), 17 PFS events have occurred, with a median PFS of 3.0 months (95% CI 1.4 - 3.8). 13 patients have died, with a median OS of 5.2 months (95% CI 2.7 - 8.5). Duration of objective response was 8.4 months in one patient and is ongoing in the other 2 responding patients. Adverse events were predominantly disease related. Atezolizumab was well tolerated with no new safety signals observed relating to this treatment. Conclusions: The objective response rate, and other efficacy endpoints, did not meet protocol defined thresholds for activity and so do not support further development of atezolizumab immunotherapy as a monotherapy for unselected patients with UTSCC. Translational endpoint analyses are ongoing. Clinical trial information: ISRCTN83474167 .