Analysis of the Microenvironment of Lung Cancer and Exploration of the Mechanism of Resistance to Immunotherapy

Lung Cancer Clinical Trial

Official title:

Analysis of the Microenvironment of Lung Cancer and Exploration of the Mechanism of Resistance to Immunotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05636605
• Other study ID #: K2022179
• Status: Recruiting
• Start date: January 1, 2018
• Est. completion date: December 31, 2028

Study information

• Verified date: December 2022
• Source: The Fourth Affiliated Hospital of Zhejiang University School of Medicine
• Contact: Kai Wang, PhD
• Phone: 13957158572
• Email: doctorhuxi[@]163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The investigators plan to conduct a multiomics analysis（such as, Genomics, proteomics, single cell RNA sequencing, space transcriptomics）of tumor tissue and blood, aiming at analyzing tumor heterogeneity, mapping the microenvironment map of lung cancer and exploring the mechanism of sensitivity and resistance to anti-PD1/PD-L1 antibodies.

Description:

Lung cancer is a highly heterogeneous disease. Cancer cells and cells within the tumor microenvironment together determine disease progression, as well as response to or escape from treatment. Tumor ecosystems are comprised of cancer cells, infiltrating immune cells, stromal cells, and other cell types together with noncellular tissue components, which interact and collectively determine disease progression as well as response to therapy. It is well known that cancer patients elicit very individualized responses to different treatments, demanding better characterization of the whole tumor ecosystem beyond currently applied clinical typing of somatic mutations in cancer cells.

Immune checkpoint blockers (ICBs) have revolutionized the management of patients with lung cancer. Blocking the interaction between the programmed cell death protein 1 (PD-1) receptor and its primary ligand (PD-L1) has demonstrated remarkable anticancer activity, and anti-PD-1/PD-L1 drugs have been approved both as single agents or in combination with cytotoxic chemotherapy. However, most patients receiving anti-PD-1/PD-L1 monoclonal antibodies do not derive benefit. Hence, there is a crucial need to identify reliable predictive biomarkers of the response to anti-PD-1/PD-L1 agents to develop precision medicine for NSCLC immunotherapy as well as to identify novel mechanisms underlying resistance to ICBs.

To map the cell type-specific landscape of cancer cells and their tumor microenvironment in lung cancer, the investigators plan to conduct a multiomics analysis（such as, Genomics, proteomics, single cell RNA sequencing, space transcriptomics）of tumor tissue and blood, aiming at analyzing tumor heterogeneity, mapping the microenvironment map of lung cancer and exploring the mechanism of sensitivity and resistance to anti-PD1/PD-L1 antibodies.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Histopathology or hemology diagnostics of lung cancer

• Patients have never received any antineoplastic therapy

Exclusion Criteria:

• Within 5 years or at the same time, there are other active malignancies

• Currently participating in interventional clinical research treatment, or received other research drugs or used research devices within 4 weeks before the first administration

• Active autoimmune diseases requiring systemic treatment (such as the use of disease relieving drugs, glucocorticoids or immunosuppressants) occurred within 2 years before the first administration

• The study was receiving systemic glucocorticoid treatment (excluding local glucocorticoids by nasal spray, inhalation or other means) or any other form of immunosuppressive therapy within 7 days before the first administration; Note: It is allowed to use glucocorticoid with physiological dose (prednisone = 10mg/day or equivalent)

• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms

Intervention

Diagnostic Test:
• Multiomics analysis
Genome, proteomics, single cell RNA sequencing, and space transcriptome sequencing,etc

Locations

Country	Name	City	State
China	The Fourth Affiliated Hospital of Zhejiang University	Yiwu	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
The Fourth Affiliated Hospital of Zhejiang University School of Medicine	Second Affiliated Hospital, School of Medicine, Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	objective response rate	Refers to the proportion of patients whose tumor shrinkage reaches a certain amount and remains for a certain period of time, including CR + PR cases	three years
Primary	Major Pathologic Response	<10% viable tumor in resected lung and lymph nodes	three-four months
Primary	progression-free survival	Patients with oncological diseases have a period of time from the start of treatment to the observation of disease progression or death due to any cause	three years