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

Condition(s) studied

Investigational drug(s) / intervention(s)

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

Study 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.

Eligibility

Primary outcome measure(s)

• 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 sites (1)

More Rabin Medical Center trials in Israel

Other trials for the same condition