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

NCT06951399 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 0026-25-RNC_MK3475-F34
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

metastatic NSCLC adenocarcinoma first-line pembrolizumab

Outcome Measures

Primary Outcomes (1)

• Change in T-cell Receptor (TCR) Repertoire Clonality and Diversity Relative to Disease Response Assessed by RECIST v1.1

  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.

  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

Study Arms (1)

Pembrolizumab 200 mg combined with pemetrexed and platinum (cisplatin or carboplatin)

EXPERIMENTAL

Drug: Pembrolizumab (KEYTRUDA®)

Interventions

Pembrolizumab (KEYTRUDA®) DRUG

IV Pembrolizumab 200 mg combined with pemetrexed and platinum (investigator's choice of cisplatin or carboplatin) every 3 weeks

Pembrolizumab 200 mg combined with pemetrexed and platinum (cisplatin or carboplatin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rabin Medical Center: lead
• MSD Pharmaceuticals LLC: collaborator

Study Sites (1)

Davidoff Comprehensive Cancer Center, Rabin Medical Center

Petah Tikva, 4941492, Israel

Location

Related Publications (1)

• Disis ML. Immune regulation of cancer. J Clin Oncol. 2010 Oct 10;28(29):4531-8. doi: 10.1200/JCO.2009.27.2146. Epub 2010 Jun 1.

  PMID: 20516428 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Ari Raphael

  Rabin Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ari Raphael, M.D

CONTACT

+972-3-9378000; arire@clalit.org.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Translational Oncology

Study Record Dates

• First Submitted: April 17, 2025
• First Posted: April 30, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): April 30, 2028
• Last Updated: July 22, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)