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

NCT06045767 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: 0222-24 TLV
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer Metastatic

Keywords

T-cell repertoire; ctDNA

Outcome Measures

Primary Outcomes (1)

• 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.

  5 years

Secondary Outcomes (1)

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

  5 years

Study Arms (1)

Pembrolizumab + Carboplatin+ Pemetrexed

EXPERIMENTAL

Drug: Pembrolizumab 50 MG Injection [Keytruda]

Interventions

Pembrolizumab 50 MG Injection [Keytruda] DRUG

Chemo-immunotherapy combination

Also known as: Carboplatin, Pemetrexed

Pembrolizumab + Carboplatin+ Pemetrexed

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Adequate organ function.

You may not qualify if:

• 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.
• Received prior radiotherapy within 2 weeks of start of study intervention.
• Major surgery within 14 days.
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated or asymptomatic brain metastases may participate provided they are radiologically stable.

Sponsors & Collaborators

• Ari Raphael: lead
• Bar-Ilan University, Israel: collaborator
• Merck Sharp & Dohme LLC: collaborator

MeSH Terms

Interventions

pembrolizumab; Injections; Carboplatin; Pemetrexed

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Ari Raphael, M.D

  Tel-Aviv University school of medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ari Raphael, M.D

CONTACT

+972-3-6973082; arir@tlvmc.gov.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head Oncology Day-care unit

Study Record Dates

• First Submitted: September 13, 2023
• First Posted: September 21, 2023
• Study Start: June 1, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029
• Last Updated: June 3, 2024

Record last verified: 2024-05