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

Phase 2Not Yet RecruitingNCT06951399

Rabin Medical Center30 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

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

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Central Contacts