Prospective evaluation of immunological, molecular-genetic, image-based and microbial analyses to characterize tumor response and control in patients with unresectable stage III NSCLC treated with concurrent chemoradiotherapy followed by consolidation therapy with durvalumab (PRECISION): protocol for a prospective longitudinal biomarker study

Abstract

Background: Concurrent platinum-based chemoradiotherapy (CRT) followed by durvalumab maintenance treatment represents the new standard of care in unresectable stage III non-small cell lung cancer (NSCLC). In this prospective hypothesis-generating single-center study, we aim to identify a framework of prognostic and predictive biomarkers by longitudinal characterization of tumor- and patient (host)-related parameters over all phases of multimodal treatment.

Methods: This study will enroll 40 patients (≥18 years, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2, with a diagnosis of PD-L1 positive (≥1%), inoperable stage III NSCLC) with an indication for CRT followed by maintenance treatment with durvalumab according to European Medicines Agency (EMA) approval. Comprehensive analysis will include peripheral blood cellular and humoral immunophenotyping and circulating tumor DNA as well as gut/saliva microbiota analyses. Additional morphological analysis with 18F-FDG-PET/computed tomography (CT) before, 6 weeks, 6 and 12 months after the end of CRT is included. Statistical analysis using multiple testing will be used to examine the impact of different parameters on progression-free survival (PFS) and overall survival (OS) as well as tumor response and response duration.

Discussion: This protocol describes the methodology of a comprehensive biomarker study in order to identify a framework of prognostic and predictive markers for unresectable stage III NSCLC in a real-world setting.

Trial registration: ClinicalTrials.gov identifier (NCT05027165), data registered on August 2021.

Keywords: Chemoradiotherapy (CRT); biomarker; immunotherapy; lung cancer; study protocol.

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-21-1010/coif). AJ receives honoraria, worked in consulting or advisory role and received expenses for travel and accomodations by Amgen, Astra Zeneca, Bayer Pharmaceuticals, BMS, Boehringer Ingelheim, Merck KGaA, Novartis, Qiagen, Roche Pharma and Takeda. AT serves in the advisory boards: Lilly, Pfizer, MSD, BMS, GSK, Celgene, Roche, Takeda, Boehringer Ingelheim, Amgen, AstraZeneca. Projects financed by AstraZeneca und Takeda. AT receives travel support from Pfizer and Amgen. CB receives grants or contracts from any entity but not related to this manuscript from Viewray, Brainlab and ELEKTA. CB receives honoraria from BMS, ROCHE, MERCK, Astrazeneca and Viewray. CB receives support for attending meetings and/or travel from BMS, ROCHE, MERCK, Astrazeneca and Viewray. CB receives BMS, ROCHE, MERCK, Astrazeneca and Viewray. CB serves in a fiduciary role in the ESTRO. CE receives grants or contracts from any entity but not related to this manuscript from German Cancer Aid. CE receives consulting fees from Novartis. CE receives support for attending meetings and/or travel from Novartis. CS has received lecture honoraria from Falk and Janssen. EN receives honoraria from Astrazeneca, Hexal, Ipsen and Roche. EN serves in consulting or advisory board of Definiens and Visiopharm. EN receives research funding from Phio Pharmaceuticals (Inst). EN receives royalties or licenses from Medigne (Inst). FK is co-founder of the company ‘Aignostics GmbH’ and receives honoraria from BMS, Merck, Agilent, Novartis, Roche, Lilly, MSD. FM receives an unrestricted Research Institutional Grant from AstraZeneca. FM receives honoraria from AstraZeneca, Novartis, Roche, Lilly, Elekta and Brainlab. FM serves in the advisory board of AstraZeneca, Novartis. LK receives honoraria from AMGEN. NR reports receiving honoraria for speaker activities and participation in advisory boards for AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Roche, and Takeda. The other authors have no conflicts of interest to declare.

2022 Translational Lung Cancer Research. All rights reserved.

Figures

Figure 1

Study design. This figure has been reproduced from Käsmann et al. (15) and written permission from the copyright holder (Springer Nature) has been obtained in order to reproduce the material. RT, radiotherapy; PET, positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography.