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

Sep 23, 2026

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PRELUCA is a randomised, intervention non-inferiority study using real-time, longitudinal circulating tumour DNA (ctDNA) to assess immunotherapy efficacy in patients with advanced non-small cell lung cancer (NSCLC). Overall survival compares standard-of-care CT evaluation with the ctDNA-guided intervention. Tumour-informed design uses baseline next-generation sequencing to build patient-specific droplet digital PCR assays run from blood collected 1 week before treatment, enabling ctDNA response assessment against RECIST-based criteria. Enrollment began July 2023 across five Danish locations under regional ethics approval.

LanguageEnglish

CategoryHealthcare

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Abstract

Introduction

Methods and analysis

Ethics and dissemination

Strengths and limitations

Open access Protocol ctDNA guided immunotherapy inpatients with advanced non-small cell lung cancer: a nationwide Danish, randomised, intervention study (PRELUCA—PRediction in LUng CAncer Treatment)– study protocol Michael Elmkvist Andersen ,1,2 Christa Haugaard Nyhus,3 Weronika Maria Szejniuk,4,5 Stine Wahlstrøm,6 Signe Timm ,7,8 Niels Pallisgaard,9,10 Malene Green Madsen,9 Maria Dalgaard Mikkelsen,9 Lise Barlebo Ahlborn,11 Julie Gehl ,1,2 Malene Støchkel Frank1,2 To cite: Andersen ME, Nyhus CH, Szejniuk WM, et al. 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. BMJ Open 2026;16:e100311 . doi:10 . 1136/ bmjopen-2025-100311 ► Prepublication history and additional supplemental material for this paper are available online. To view these files, please visit the journal online ([https://doi.org/10.1136/](https://doi.org/10.1136/)[ ](https://doi.org/10.1136/)[bmjopen-2025-100311](bmjopen-2025-100311)) . Received 06 February 2025 Accepted 14 January 2026 © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. For numbered affiliations see end of article. Correspondence to Michael Elmkvist Andersen; [mielan@regionsjaelland.dk](mielan@regionsjaelland.dk) ABSTRACT 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. INTRODUCTION PRELUCA is a randomised, intervention, non-inferiority study evaluating treatment efficacy by circulating tumour DNA (ctDNA) compared with standard of care in patients with advanced non-small cell lung cancer (NSCLC), treated with first-line immunotherapy. The primary endpoint of the study is overall survival (OS) . The study is considered a pragmatic clinical trial, including broad inclusion criteria, with the strength and STRENGTHS AND LIMITATIONS OF THIS STUDY ⇒ Broad inclusion criteria and uniform monotherapy immunotherapy create a real-world, generalisable cohort. ⇒ Circulating tumour DNA (ctDNA) monitoring enhances clarity, objectivity and shared decision-making, supported by intuitive longitudinal graphs that improve patient–clinician communication. ⇒ The methodological setup (tumour-informed next generation sequencing, droplet digital PCR, standardised sampling with Streck tubes) provides a robust, clinically feasible framework for accurate and reproducible ctDNA evaluation. ⇒ Comparisons between ctDNA and CT scans are inherently challenged by different evaluation intervalsand detection thresholds, limiting direct equivalence. ⇒ A subset of patients will have non-detectable ctDNA, reducing evaluability and introducing heterogeneity in outcome asses

FAQs

What is the main goal of the PRELUCA study protocol?

To evaluate the efficacy of ctDNA-guided immunotherapy versus standard of care in advanced NSCLC using a randomised non-inferiority intervention design.

How does the study compare standard-of-care evaluation with the intervention arm?

The primary outcome compares overall survival between groups assessed by CT scan evaluation (standard of care) and ctDNA evaluation (intervention).

What methods generate the ctDNA measurements used for treatment monitoring?

The study uses tumour-informed baseline next-generation sequencing to design patient-specific droplet digital PCR assays, run on blood collected about one week before intended treatment, with responses evaluated via ctDNA RECIST-based criteria.

Sep 23, 2026

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