NCT06951399

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

T-Cell Repertoire Sequencing: Assessing Pembrolizumab Efficacy in Advanced Non-Small Lung Cancer

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Rabin Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Conditions

• NSCLC (Advanced Non-small Cell Lung Cancer)
• NSCLC Stage IV Without EGFR/ALK Mutation
• NSCLC Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Pembrolizumab (KEYTRUDA®)	IV Pembrolizumab 200 mg combined with pemetrexed and platinum (investigator's choice of cisplatin or carboplatin) every 3 weeks

Timeline

• Start date: 2025-09-01
• Primary completion: 2027-08-30
• Completion: 2028-04-30
• First posted: 2025-04-30
• Last updated: 2025-07-22

Locations

1 site across 1 country: Israel

Regulatory

• FDA-regulated drug study