Analysis of Drug Resistance in Immune Checkpoint Inhibitors of Non-small Cell Lung Cancer

April 16, 2024 updated by: Xiaomin Niu, Shanghai Chest Hospital

Molecular Landscape of Primary and Acquired Resistance to Immune Checkpoint Inhibitors in Patients With Chinese Advanced Non-small Cell Lung Cancer

Immunotherapy has improved the prognosis of non-small cell lung cancer (NSCLC) patients, but about 80% of patients do not respond at all, which is called primary resistance. Absence of the PD-L1 expression is regarded as one of primary resistant reasons to immunotherapy, there are some other reasons which have been reported to be related with the primary resistance, including tumor mutation burden (TMB), microsatellite instability (MSI), tumor neoantigen burden (TNB), HLA genotype, loss of heterozygosity (LOH), intra tumoral heterogeneity (ITH), genome wide doubling (WGD), and ploidy. While some patients initially respond to immunotherapy, later relapse and develop disease progression, which is called acquired resistance, like escaping of interferon signaling pathways or mutations in some important genes such as B2M/JAK1/JAK2.

So the objective of this research is to explore the comprehensive immune molecular markers of primary and acquired resistance to immunotherapy in patients with Chinese advanced NSCLC based on the results of whole exome sequencing (WES) and targeted sequencing (TS)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

250

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Chinese advanced NSCLC patients received immunotherapy who underwent WES and TS sequencing. The investigators studied samples from the patients before- and after- ICIs.

Description

Inclusion Criteria:

  • Be able to provide informed consent, and understand and agree to follow the research requirements;
  • Advanced non-small cell lung cancer;
  • Patients receiving immune checkpoint inhibitor treatment represented by anti-PD-1/PD-L1 monoclonal antibody;
  • The patient must be able to provide fresh tumor tissue before- and after- ICIs (50mg of tumor tissue sample/ 2 needles of 18G thick needle puncture) or tumor tissue archived within one year (FFPE tissue block or about 15 pieces [10- 15 sheets] Freshly cut, unstained FFPE slides) and pathology reports (except for advanced non-small cell lung cancer other than neuroendocrine cancer); provide matched 10mL peripheral whole blood samples at the same time;
  • ECOG physical fitness status ≤1;
  • The patient must have at least one measurable lesion (assessed according to RECIST v1.1);
  • Life expectancy ≥ 12 weeks;
  • The patient must have adequate organ function, and must be reached absolute neutrophil count (ANC) ≥1.5x10^9/L, platelets ≥100x10^9/L, hemoglobin ≥90g/L, international normalized ratio (INR) or prothrombin time ≤ 1.5x ULN , activated partial thromboplastin time (aPTT)≤1.5x ULN, serum total bilirubin≤1.5x ULN (Patients with Gilbert syndrome can be enrolled if total bilirubin<3x ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5x ULN(Patient with liver metastases, this standard is AST and ALT≤5x ULN) within 7 days before treatment;

Exclusion Criteria:

  • Patients with other tumors. Except for basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin or cervical cancer in situ, subjects who have received potential radical treatment and have not relapsed within 5 years before the start of treatment can be included in the study;
  • Have received any approved systemic anti-tumor immunotherapy before starting the research treatment;
  • A history of interstitial lung disease, non-infectious pneumonia or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, etc.;
  • Severe chronic or active infections that require systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection;
  • Known human immunodeficiency virus infection; previous allogeneic stem cell transplantation or organ transplantation;
  • The investigator judged that the patient's compliance during the study period was insufficient

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR)
Time Frame: Up to 5 years
The investigator (and the chief radiologist) used the RECIST 1.1 evaluation criteria to evaluate the efficacy indicators. CT or MRI imaging data of the chest and abdomen collected regularly during the screening/baseline period and the study period were used for tumor evaluation. Only when there may be primary or metastatic disease in the pelvis, pelvic imaging is recommended. Any other disease-affected areas (for example, the pelvis and brain) should undergo additional imaging studies based on the individual patient's signs and symptoms. If an unplanned evaluation is performed and it is shown that the patient has not progressed, follow-up evaluation should be performed at the next scheduled visit as much as possible. Scanning/tumor evaluation continued throughout the study period until RECIST 1.1 appeared
Up to 5 years
Progression-free survival (PFS)
Time Frame: Up to 5 years
Calculate the time from the immunotherapy to the tumor progression/all-cause death/the end of the follow-up period.
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: Up to 5 years
Calculate the time from the immunotherapy to the end of the all-cause death/follow-up period.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Chest Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 21, 2016

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

July 9, 2021

First Submitted That Met QC Criteria

July 24, 2021

First Posted (Actual)

July 27, 2021

Study Record Updates

Last Update Posted (Actual)

April 17, 2024

Last Update Submitted That Met QC Criteria

April 16, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • THORACIC001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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