Journal Article

Evaluating atezolizumab in patients with urinary tract squamous cell carcinoma (AURORA): study protocol for a single arm, open-label, multicentre, phase II clinical trial

Boukas, Konstantinos, Birtle, Alison, Martin, Jonathan, Griffiths, Gareth, Lawrence, Megan, Crabb, Simon, Jane-Bibby, Sarah, Wickens, Robin, Knight, Allen, Linch, Mark, Dunkley, Denise, Jones, Robert, Coleman, Adam, Markham, Hannah, Huddart, Robert

2023

Overview

Background Bladder and urinary tract cancers account for approximately 21,000 new diagnoses and 5,000 deaths annually in the UK. Approximately 90% are transitional cell carcinomas where advanced disease is treated with platinum based chemotherapy and PD-1/PD-L1 directed immunotherapy. Urinary tract squamous cell carcinoma (UTSCC) accounts for about 5% of urinary tract cancers overall making this a rare disease. We have yet to establish definitive systemic treatment options for advanced UTSCC. Preliminary translational data, from UTSCC patient tumour samples, indicate high PD-L1 expression and tumour infiltrating lymphocytes in a proportion of cases. Both of these features are associated with differential gene expression consistent with a tumour/immune microenvironment predicted to be susceptible to immune checkpoint directed immunotherapy which we will evaluate in the AURORA trial. Methods AURORA is a single arm, open-label, multicentre,UK phase II clinical trial. 33 patients will be recruited from UK secondary care sites. Patients with UTSCC, suitable for treatment with palliative intent, will receive atezolizumab PD-L1 directed immunotherapy (IV infusion, 1680 mg, every 28 days) for one year if tolerated. Response assessment, by cross sectional imaging will occur every 12 weeks. AURORA uses a Simon’s 2-stage optimal design with best overall objective response rate (ORR, by RECIST v1.1) at a minimum of 12 weeks from commencing treatment as the primary endpoint. Secondary endpoints will include overall survival, progression-free survival, duration of response, magnitude of response using waterfall plots of target lesion measurements, quality of life using the EORTC QLQ-C30 tool, safety and tolerability (CTCAE v5) and evaluation of potential biomarkers of treatment response including PD-L1 expression. Archival tumour samples and blood samples will be collected for translational analyses. Discussion If this trial shows atezolizumab to be safe and effective it may lead to a future late phase randomised controlled trial in UTSCC. Ultimately, we hope to provide a new option for treatment for such patients. Trial registrations EudraCT Number: 2021-001995-32 (issued 8 th September 2021); ISRCTN83474167 (registered 11 May 2022); NCT05038657 (issued 9th September 2021).

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Atezolizumab / B7-H1 Antigen / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Cancer therapies / Carcinoma, Squamous Cell - drug therapy / Chemotherapy / Clinical trials / Clinical Trials, Phase II as Topic / Cystectomy / Diagnosis / Drug therapy / Gene expression / Genetic aspects / Health Promotion and Disease Prevention / Humans / Immune checkpoint / Immunotherapy / Lymphocytes / Medical prognosis / Medicine/Public Health / Microenvironments / Monoclonal antibodies / Multicenter Studies as Topic / Oncology / Patient outcomes / Patients / PD-1 protein / PD-L1 expression / PD-L1 protein / Phase II / Quality of Life / Radiation therapy / Randomized Controlled Trials as Topic / Response rates / Squamous cell carcinoma / Steroids / Study Protocol / Surgical Oncology / Targeted cancer therapy / Toxicity / Transitional cell carcinoma / Translation / Translational research / Tumor Microenvironment / Tumors / Urinary Tract / Urinary tract cancer / Urinary tract squamous cell carcinoma / Urogenital system / Urological surgery