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

ConditionNon-small Cell Lung Cancer Metastatic

Trial statusNot yet recruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorAri Raphael

About this trial

This is a single site, non-randomized trial for the assessment of intravenous (IV) pembrolizumab (also known as MK-3475) combined with pemetrexed/platinum-based chemotherapy in subjects with advanced or metastatic non-squamous non-small lung cancer (NSCLC) who have not previously received systemic therapy for advanced disease and in whom directed therapy is not indicated. Approximately 30 subjects will be enrolled in this trial to examine the clonality and diversity dynamics matched with disease response evaluated by RECIST 1.1.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participant (or legally acceptable representative if applicable) provides written informed consent for the trial.

Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

Archival tumor tissue sample or newly obtained [core, incisional or excisional] biopsy of a tumor lesion not previously irradiated has been provided.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

Disqualifiers

Pregnancy or breastfeeding

Aberration in a known targetable molecular driver.

Received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.

Received prior systemic anti-cancer therapy for metastatic disease.

Trial design

Design model

Single group

Treatments tested in this trial

Pembrolizumab 50 MG Injection [Keytruda]
Drug
Chemo-immunotherapy combination

Treatment groups

30 Participants

are divided into 1 treatment group

Group A: Pembrolizumab + Carboplatin+ PemetrexedExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Objective Response Rate (ORR) per RECIST 1.1 - correlated to TCR repertoire data, such as clonality/diversity.

ORR defined as the percentage of participants who achieve a confirmed complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by the investigator. By integrating serial TCR repertoire sequencing (Rep-seq) of NSCLC patients treated with pembrolizumab and platinum-based chemotherapy regimens we aim to capture the temporal clonality and diversity dynamics with the disease response.

Time frame

5 years

Secondary outcomes

Objective Response Rate (ORR) correlated with circulating tumor DNA (ctDNA), by measurement of variant allele frequency (VAF).

To capture the VAF in ctDNA, and correlate it with response to therapy evaluated by ORR per RECIST 1.1. We will capture its dynamics throughout blood samples collected longitudinally (pre-and during treatment).

Time frame

5 years

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Ari Raphael

Lead sponsor

Tel Aviv Medical Center

Sponsor institution

Bar-Ilan University, Israel

Collaborator

Merck Sharp & Dohme LLC