Effect of Chemotherapy on TMB in NSCLC

Effect of Platinum-based Chemotherapy on Tumor Mutation Burden in Patients With Advanced Non-small Cell Lung Cancer

Tumor mutation burden is identified as an important biomarkers for predicting PD-1/PD-L1 inhibitors in advanced Non-Small Cell Lung Cancer. Several previous clinical trials have demonstrated that chemotherapy could enhance the efficacy of PD-1/L1 immunotherapy in NSCLC such as Checkmate-227, Impower-150, Keynote-189, etc. Pre-clincial experiment shows that chemotherapy could increase CD8 TIL infiltration in tumor microenvironment, activate T cell immune reaction. However, it remains unclear whether chemotherapy could affect tumor mutation burden in advanced NSCLC patients. The present study aims to evaluate whether tumor mutation burden will change after receiving chemotherapy in advanced NSCLC patients.

Study Overview

• Status: Unknown
• Conditions: Chemotherapy Effect; Immunotherapy; Tumor Mutation Burden; PD-1/L1 Inhibitor
• Intervention / Treatment: Other: Next-Genernation Sequence

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200003
      • Recruiting
      • Shanghai Changzheng Hospital
      • Principal Investigator: Yuan-Sheng Zang, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Advanced NSCLC without druggable molecular events (EGFR, ALK, c-Met, BRAF, Ret, etc)

Description

Inclusion Criteria:

• Advanced NSCLC diagnosed histologically; Expected survival ≥ 6 month;
• Without Druggable molecular events (EGFR, ALK, c-Met, BRAF, Ret, etc)
• ECOG / PS score: 0-2, and the main organ function to meet the following criteria: HB ≥ 90g / L, ANC ≥ 1.5 × 109 / L, PLT ≥ 80 × 109 / L,BIL <1.5 times the upper limit of normal (ULN); Liver ALT and AST <2.5 × ULN and if liver metastases, ALT and AST <5 × ULN; Serum Cr ≤ 1 × ULN, endogenous creatinine clearance ≥50ml/min

Exclusion Criteria:

• Patient can not comply with research program requirements or follow-up;
• Patient will receive immunotherapy;

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Chemotherapy Group; All participants are advanced NSCLC without druggable gene mutation (EGFR, ALK, ROS-1, Met, Ret. BRAF, etc), who would receive platinum-based chemotherapy.	Other: Next-Genernation Sequence; Tumor Mutation burden will be evaluated using NGS after 2-cycle chemotherapy, 4-cycle chemotherapy, or at progressive disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Mutation Burden Change	Tumor mutation burden will be calculated using a 520 genes NGS panel	every 6 weeks up to progression disease

Collaborators and Investigators

• Sponsor: Baodong Qin

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2018
• Primary Completion (ANTICIPATED): February 28, 2019
• Study Completion (ANTICIPATED): August 31, 2019

Study Registration Dates

• First Submitted: September 16, 2018
• First Submitted That Met QC Criteria: September 23, 2018
• First Posted (ACTUAL): September 25, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 25, 2018
• Last Update Submitted That Met QC Criteria: September 23, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: COTMB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No