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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04977791
Recruitment Status : Recruiting
First Posted : July 27, 2021
Last Update Posted : July 27, 2021
Information provided by (Responsible Party):
Xiaomin Niu, Shanghai Chest Hospital

Brief Summary:

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)

Condition or disease Intervention/treatment
Non-Small Cell Lung Cancer Drug: Anti-PD-1/PD-L1 monoclonal antibody

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Study Type : Observational
Estimated Enrollment : 250 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Molecular Landscape of Primary and Acquired Resistance to Immune Checkpoint Inhibitors in Patients With Chinese Advanced Non-small Cell Lung Cancer
Actual Study Start Date : July 21, 2016
Estimated Primary Completion Date : December 1, 2022
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine

Intervention Details:
  • Drug: Anti-PD-1/PD-L1 monoclonal antibody
    Observe a situation before and after immunotherapy
    Other Name: Immune checkpoint inhibitor

Primary Outcome Measures :
  1. 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

  2. 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.

Secondary Outcome Measures :
  1. 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.

Biospecimen Retention:   Samples With DNA
The specimens are stored in the refrigerator at -20°C or -80°C as specified in the clinical trial protocol. Test specimens and backup specimens should be kept in separate refrigerators to prevent malfunction of one of the refrigerators. Centrifugation time, specimen collection and specimen storage time should be carried out in strict accordance with the requirements of the clinical trial protocol.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04977791

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China, Shanghai
Xiaomin Niu Recruiting
Shanghai, Shanghai, China
Contact: Niu Xiaomin   
Sponsors and Collaborators
Shanghai Chest Hospital
Publications of Results:

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Responsible Party: Xiaomin Niu, Principal Investigator, Shanghai Chest Hospital Identifier: NCT04977791    
Other Study ID Numbers: THORACIC001
First Posted: July 27, 2021    Key Record Dates
Last Update Posted: July 27, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Xiaomin Niu, Shanghai Chest Hospital:
Non-Small Cell Lung Cancer
Next-Generation Sequencing
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Immune Checkpoint Inhibitors
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents