2408Tip DISCUS: A Randomised Phase II Study of 3 Vs 6 Cycles of Chemotherapy Followed by Maintenance Avelumab in Advanced Urothelial Cancer - Wearable Devices and Circulating Biomarkers Assessing Quality of Life and Surrogate Efficacy Endpoints

DISCUS (EudraCT2021-001975-17) is a randomised phase III trial comparing 3 vs 6 cycles of first-line CT, followed by maintenance avelumab on the QoL of patients with aUC. Fewer cycles of CT may be associated with better quality of life (QoL) and improve efficacy, as more patients will be exposed to immune checkpoint inhibitors. Wearable devices are a novel method of assessment of QoL for patients receiving systemic anticancer therapy (SACT) and may have advantages over existing methods such as EORTC-QLQ-C30 questionnaires. This is being tested in the DISCUS trial. Recent work demonstrates that normalisation of ctDNA is associated with better outcomes in the adjuvant setting. Dynamic changes in ctDNA will also be tested in this study. Tracking ctDNA may be able to identify mechanisms of resistance to SACT. Patients enrolled in the ongoing DISCUS trial can consent this exploratory sub study, investigating the role of ctDNA and digital wearable device data in assessing QOL in aUC patients receiving SACT. Patient reported outcomes (PROs) on QOL will be correlated with biometric data from wearable devices, tracking step counts, heart rate and peripheral oximetry. Participants will be required to wear the device for 8 hours per day, at least once per treatment cycle, between cycle 1-6 (C1-6) and 8-12 weeks after C6. Average daily step counts at C6 will be compared between groups and correlated to adverse events and PROs. ctDNA measurement will occur at baseline, C3,6 and 8-12-weeks after C6. ctDNA assessment will be conducted using a personalised approach, using whole exome sequencing to track >2 mutations from the primary tumour (Natera) and will be compared to radiological assessment and correlated with efficacy outcomes. ctDNA may be more accurate in assessing outcomes than radiology. Shorter periods of CT may be associated with better QoL for patients without affecting efficacy. ctDNA and wearable devices is a step towards personalised medicine for these patients. EudraCT 2021-001975-17. Queen Mary University of London. This study is financially supported by Merck (CrossRef Funder ID: 10.13039/100009945), as part of an alliance between Merck and Pfizer.