Skip to main content
OpenTrials
Not Yet Recruiting

NCT Number: NCT06951399

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.

Not Yet Recruiting

Trial opening soon.

Get Notified

Key information

Conditions

NSCLC (Advanced Non-small Cell Lung Cancer) Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms NSCLC Adenocarcinoma NSCLC Stage IV Without EGFR/ALK Mutation Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Pembrolizumab (KEYTRUDA®)

Drug

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

Primary outcomes

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

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Ari Raphael, M.D

CONTACT

[email protected]

+972-3-9378000

Sponsors and collaborators

Lead sponsor

Rabin Medical Center

Other

Collaborators

  • MSD Pharmaceuticals LLC

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Apr 30, 2025
Registry last updated
Jul 22, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.