Glycoprotein in Immunotherapy Response and Efficacy Prediction of Lung Cancer

NCT ID: NCT06730503

Last Updated: 2024-12-12

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 250 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-10-01
• Study Completion Date: 2028-10-31

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 (primary resistance), and some patients initially respond to immunotherapy, later relapse and develop disease progression (acquired resistance).

So the objective of this research is to explore the sugar chain heterogeneity of primary and acquired resistance to immunotherapy in patients with NSCLC.

Detailed Description

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.

Sugar chains, as the third chain of life except nucleic acids and proteins. More than half of the proteins in the human body have sugar chain modifications. During the occurrence, development, and metastasis of malignant tumors such as lung cancer, colorectal cancer, and gastric cancer, protein glycosylation undergoes corresponding changes as the disease progresses. Discovering and elucidating disease-related glycoproteins and their characteristic sugar chains is of great significance for searching for disease-specific biomarkers.

So the objective of this research is to explore the comprehensive characteristic sugar chain markers of primary and acquired resistance to immunotherapy in patients with Chinese advanced NSCLC.

Conditions

Non Small Cell Lung Cancer

Keywords

Non Small Cell Lung Cancer; immunotherapy; Immune checkpoint inhibitors; PD-L1; resistance; sugar chain heterogeneity; glycoprotein

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Anti-PD-1/PD-L1 monoclonal antibody

Immune checkpoint inhibitor

Intervention Type: DRUG

Observe a situation before and after immunotherapy

Interventions

Immune checkpoint inhibitor

Observe a situation before and after immunotherapy

Intervention Type: DRUG

Eligibility Criteria

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 10mL peripheral whole blood samples before- and after- ICIs;
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Chest Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xiaomin Niu

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Xiaomin Niu

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Facility Contacts

Xiaomin Niu

Role: primary

Other Identifiers

THORACIC006

Identifier Type: -

Identifier Source: org_study_id