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

Phase 2

Not yet recruiting

• Conditions: NSCLC (Advanced Non-small Cell Lung Cancer); NSCLC Stage IV Without EGFR/ALK Mutation; NSCLC Adenocarcinoma
• Interventions: Drug: Pembrolizumab (KEYTRUDA®)

• Registration Number: NCT06951399
• Lead Sponsor: Rabin Medical Center

Brief 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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-17
• Study First Submitted QC: 2025-04-26
• Last Update Submitted: 2025-04-26
• Study First Posted: 2025-04-30
• Last Update Posted: 2025-04-30
• Study Start: 2025-05-01
• Primary Completion: 2027-04-30
• Study Completion: 2028-04-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Histologically confirmed diagnosis of NSCLC adenocarcinoma stage IV or unresectable stage III.
• Have measurable disease based on RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Adequate organ function.

Exclusion Criteria

• Aberration in one or more of molecular drivers.
• Has received prior systemic anti-cancer therapy prior to allocation.
• Known active CNS metastases and/or carcinomatous meningitis.
• Known additional malignancy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pembrolizumab 200 mg combined with pemetrexed and platinum (cisplatin or carboplatin)	Pembrolizumab (KEYTRUDA®)	-

Primary Outcome Measures

Name	Time	Method
Change in T-cell Receptor (TCR) Repertoire Clonality and Diversity Relative to Disease Response Assessed by RECIST v1.1	From date of randomization until the end of treatment, defined as a maximum of 35 cycles administered every 3 weeks (up to 2 years), or until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first	TCR sequencing will be performed on peripheral blood samples to assess clonality and diversity metrics. Changes in these metrics will be analyzed relative to clinical disease response evaluated according to RECIST version 1.1 criteria.

Trial Locations

Locations (1)

Davidoff Comprehensive Cancer Center, Rabin Medical Center; 🇮🇱 Petah-Tikva, Israel