ctDNA guided immunotherapy in patients with advanced non-small cell lung cancer: a nationwide Danish, randomised, intervention study (PRELUCA-PRediction in LUng CAncer Treatment) - study protocol

INTRODUCTION: PRELUCA is a randomised, intervention, non-inferiority study designed to use real-time, longitudinal circulating tumour DNA (ctDNA) measurements to evaluate the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC). The primary outcome is overall survival between the two groups: the standard of care group (computer tomography scan evaluation) and intervention group (ctDNA evaluation).

METHODS AND ANALYSIS: The inclusion and exclusion criteria align with European Society for Medical Oncology treatment guidelines and permit broad inclusion of NSCLC patients, ensuring 'real-world' representativeness. The study uses a tumour-informed method, using baseline next generation sequencing analyses to design patient-specific droplet digital PCR assays, which are run with collected blood samples 1 week prior to the intended treatment, enabling real-time evaluation via ctDNA Response Evaluation Criteria in Solid Tumours.

ETHICS AND DISSEMINATION: Inclusion began in July 2023 and patients are now being actively included in five locations across Denmark. Approval by The Committee on Health Research Ethics of Region Zealand was gained on 4 May 2023.

TRIAL REGISTRATION NUMBER: NCT05889247.