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

Background

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.

Trial design

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.

Clinical trial identification

EudraCT 2021-001975-17.

Editorial acknowledgement

Legal entity responsible for the study

Queen Mary University of London.

Funding

This study is financially supported by Merck (CrossRef Funder ID: 10.13039/100009945), as part of an alliance between Merck and Pfizer.

Disclosure

J. Puente: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Janssen, MSD, Pfizer, Eisai, Ipsen, Roche, BMS, Merck; Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, Janssen, MSD, Bayer, Pfizer, Eisai, Roche, BMS, Merck; Financial Interests, Institutional, Research Grant: Astellas, Roche, Merck. J. Kelly: Other, Personal, Full or part-time Employment: Ethera Health. Y. Loriot: Financial Interests, Personal, Advisory Board: Merck Kga, Pfizer, Gilead, seattle genetics, Taiho; Financial Interests, Personal, Other, lectures, advisory boards: MSD, AstraZeneca, Astellas, Janssen; Financial Interests, Personal, Other, lectures, advisroy boards: Roche, BMS; Financial Interests, Institutional, Research Grant: Janssen, Sanofi, MSD, Roche, Celsius; Financial Interests, Institutional, Steering Committee Member: Janssen; Financial Interests, Steering Committee Member: MSD, Astellas, Gilead/Immunomedics, Taiho; Financial Interests, Personal, Steering Committee Member: Basilea; Financial Interests, Institutional, Local PI: Pfizer, MSD, Pfizer, Janssen, Exelexis, AstraZeneca, Merck Kga, BMS, Astellas, Gilead, Incyte; Financial Interests, Institutional, Coordinating PI: Janssen; Non-Financial Interests, Other, scientific committee: ARC; Non-Financial Interests, Member: ESMO, ASCO, AACR. T.B. Powles: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Exelixis, Incyte, Ipsen, Merck, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, MSD; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche, Pfizer, MSD, AstraZeneca, Ipsen; Financial Interests, Personal, Other, Sponsorship for Uromigos Podcast: Mashup Ltd; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bristol Myers Squibb, Exelixis, Ipsen, Merck, MSD, Seattle Genetics, Novartis, Pfizer, Merck Serono, Astellas, Johnson & Johnson, Eisai. E. Grande Pulido: Financial Interests, Personal, Invited Speaker: Adacap, AstraZeneca, Bristol Myers Squibb, Eisai, Eusa Pharma, Ipsen, Janssen, Lilly, Merck KGa, Pfizer, Roche, Dr. Reddy's; Financial Interests, Personal, Advisory Board: Astellas, Bayer, MSD, Novartis, Sanofi-Genzyme; Financial Interests, Institutional, Advisory Board: Caris Life Sciences, OncoDNA (Biosequence); Financial Interests, Institutional, Research Grant, Independent research grant: Astellas, AstraZeneca, Lexicon, MTEM/Threshold, Nanostring Technologies, Pfizer, Roche, Merck; Financial Interests, Institutional, Coordinating PI, Independent research grant: Ipsen; Non-Financial Interests, Other, Advisor Board member: ENETS; Non-Financial Interests, Member of Board of Directors: GETNE, GUARD Consortium, Grupo centro de Tumores Genitourinarios. All other authors have declared no conflicts of interest.