Tracking T-Cell Responses to Evaluate Pembrolizumab Effectiveness in Advanced Non-Small Cell Lung Cancer

This study includes patients with advanced non-small cell lung cancer (NSCLC) - either unresectable stage III or stage IV adenocarcinoma without actionable driver mutations - who are treated with pembrolizumab in combination with platinum-based doublet chemotherapy, irrespective of PD-L1 expression levels. The primary objective is to assess treatment response through integration of serial T-cell receptor (TCR) repertoire sequencing (Rep-seq), capturing longitudinal changes in T-cell clonality and diversity. These immune dynamics will be correlated with radiographic response assessed by RECIST 1.1, with the aim of improving the accuracy of response classification, including differentiation between progression, pseudo-progression, and hyperprogression. Additionally, circulating tumor DNA (ctDNA) levels will be measured longitudinally (pre-treatment and during treatment) to evaluate their potential as a complementary biomarker of disease burden and treatment efficacy in the context of chemo-immunotherapy.

NCT Number	NCT06951399
Lead Sponsor	Rabin Medical Center Collaborators: MSD Pharmaceuticals LLC
Conditions	NSCLC (Advanced Non-small Cell Lung Cancer), NSCLC Stage IV Without EGFR/ALK Mutation, NSCLC Adenocarcinoma
Enrollment	30 participants
Start Date	2025-09-01
Primary Completion	2027-08-30 (estimated)
Study Completion	2028-04-30 (estimated)
Updated on ClinicalTrials.gov	2025-07-22