NSCLC Adenocarcinoma, NSCLC (Advanced Non-small Cell Lung Cancer), NSCLC Stage IV Without EGFR/ALK Mutation
Conditions
Keywords
metastatic NSCLC adenocarcinoma first-line pembrolizumab
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.
Interventions
DRUGPembrolizumab (KEYTRUDA®)
IV Pembrolizumab 200 mg combined with pemetrexed and platinum (investigator's choice of cisplatin or carboplatin) every 3 weeks
Sponsors
MSD Pharmaceuticals LLC
Rabin Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Israel
Contacts
Primary ContactAri Raphael, M.D
Outcome results
None listed