Association Between Microbiome and the Efficacy and Safety of PD-1/PD-L1 Blockade in Resectable NSCLC

Association Between Respiratory Tract and Gut Microbiome and the Efficacy and Safety of PD-1/PD-L1 Blockade in Resectable Non-small-cell Lung Cancer: a Single-center Cohort Study

This study will investigate the relationship between respiratory and gut microbiome and PD-1/PD-L1 immune checkpoint inhibitor efficacy and immune-related adverse events (irAE) in patients with non-small cell lung cancer (Stage IIA-IIIB）

Study Overview

• Status: Not yet recruiting
• Conditions: Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: Neoadjuvant immunotherapy combined with chemotherapy; Drug: Neoadjuvant chemotherapy

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Yeming Wang, M.D.; Phone Number: +86 84206264; Email: wwyymm_love@163.com
• Study Contact Backup: Name: Dong Liu, M.D.; Email: liudongdoc@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The neoadjuvant cohort of patients with non-small cell lung cancer (NSCLC) (stages IIA to selective stage IIIB; squamous or non-squamous cell) who are receiving a PD-1/PD-L1 monoclonal antibody in conjunction with platinum-containing two-agent standard chemotherapy (Arm 1) or platinum-containing two-agent standard chemotherapy (Arm 2).

Description

Inclusion Criteria:

• 18-75 years old;
• first-diagnosed, driver gene-negative non-small cell lung cancer patients with histopathological confirmed diagnosis (Stage IIA-IIIB);
• at least 1 measurable lesion as defined by RECIST version 1.1; an Eastern Cooperative Oncology Group (ECOG) physical status score of 0-1;
• no prior systemic therapy or radiotherapy;
• the patients are eligible for indications for surgical resection and amenable to - neoadjuvant immunotherapy or chemotherapy after multidisciplinary evaluation;
• signing the written consent before enrollment in the study;
• participants need to have adequate pulmonary ventilation and diffusion function to allow surgical resection by pre-enrolment pulmonary function testing;

Exclusion Criteria:

• refusal of participation or inability to give a clear consent;
• requiring treatment with systemic glucocorticoids and other - immunosuppressive agents;
• use of antibiotics within the previous 3 months or the presence of an infectious disease requiring antibiotic therapy;
• probiotics within 3 months prior to enrolment;
• presence of obstructive pneumonia, cancerous cavities, active tuberculosis;
• the presence of bronchiectasis, combined lung infections, pulmonary fibrosis, uncontrolled diabetes mellitus;
• the presence of primary tumors elsewhere;
• receiving chemotherapy or any other cancer treatment prior to enrolment;
• participants with brain metastases confirmed by brain MRI with contrast prior to enrolment;
• active or pre-existing autoimmune disease;
• the presence of uncontrolled comorbidities, including heart failure, uncontrolled hypertension, unstable angina, interstitial lung disease;
• positive test for hepatitis B surface antigen or hepatitis C ribonucleic acid requiring treatment;
• known positive history or positive test results for human immunodeficiency virus or acquired immunodeficiency syndrome (AIDS);
• history of allergy to study drug components;
• women who are pregnant or breastfeeding;
• previous treatment with anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibodies.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Arm1(Neoadjuvant immunotherapy combined with chemotherapy)	Drug: Neoadjuvant immunotherapy combined with chemotherapy; The treatment regimen consisted of a PD-1/PD-L1 monoclonal antibody in combination with a platinum-containing two-agent standard chemotherapy regimen administered every three weeks. Following two to four cycles of therapy, patients who demonstrated no evidence of disease progression were eligible for surgical resection, which was performed within three to four weeks after the conclusion of the last neoadjuvant therapy. Consolidation with a PD-1/PD-L1 monoclonal antibody was initiated within three to eight weeks after surgery and continued every three weeks. The efficacy of the treatment was evaluated according to the irRECIST criteria. Chemotherapy regimens were selected based on tumour histology and investigator judgement. In the event of poor tolerability, patients may switch between cisplatin or carboplatin treatments.
Arm2(Neoadjuvant chemotherapy)	Drug: Neoadjuvant chemotherapy; A platinum-containing two-agent standard chemotherapy regimen was administered every three weeks. Following a two-to-four-cycle therapy, if the patients were evaluated without progressive disease, patients undergo surgical resection within three to four weeks of the final neoadjuvant treatment. Postoperative adjuvant chemotherapy is then conducted in accordance with the recommended regimen outlined in the 2022 edition of the CSCO Guidelines for the Diagnosis and Treatment of Non-Small Cell Lung Cancer. The efficacy of the treatment was evaluated in accordance with the RECIST 1.1 criteria. The chemotherapy regimens were selected based on the tumor histology and the judgement of the investigators, in accordance with the standard clinical practice. In the event of poor tolerability, patients may switch between cisplatin or carboplatin treatments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathological response (mPR)	defined as ≤10% residual live tumor tissue in lung cancer samples resected after neoadjuvant therapy as assessed by the central pathology laboratory.	Whithin time from enrollment to surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic complete response (pCR)	defined as the absence of live tumour cells in lung cancer specimens resected after neoadjuvant therapy and in all sampled local lymph nodes according to central pathology laboratory assessment. Patients who are not evaluable according to the central pathological assessment (including patients with R2 margins) or who do not have a surgical specimen will not be considered to have achieved a pCR (e.g. remission will be recorded as 'not evaluable' or 'missing', as appropriate).	Whithin time from enrollment to surgery
Disease free survival (DFS)	defined as the time from surgery to the first recurrence of disease (local or distant) or all-cause death, whichever occurs first. DFS was captured only for events after surgery.	Whithin 1 year after surgery
Overall survival (OS)	defined as time from enrolment to all-cause death	Whithin 1 year after enrollment
Immune-related adverse event (irAE)	defined as all levels of adverse drug reactions in antitumor immunotherapy that are judged to be related to immune mechanisms, excluding non-specific infusion reactions.	Whithin 1 year after enrollment
Changes in microbiomics in respiratory tract and gut	Defined as microbial composition, diversity, and functional activity measured by 16S RNA sequencing	Whithin 1 year after enrollment
Radiological response	Defined as radiographic change assesed by RECIST 1.1.	Whithin time from enrollment to surgery
Changes in single-cell immune repertoire	Defined as diversity of immune receptors (e.g. TCR and BCR) for T and B cells in lung tissues	Whithin time from enrollment to surgery

Collaborators and Investigators

• Sponsor: Capital Medical University
• Collaborators: China-Japan Friendship Hospital
• Investigators: Principal Investigator: science and technology center, China-Japan Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 25, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: September 15, 2024
• First Submitted That Met QC Criteria: September 23, 2024
• First Posted (Actual): September 25, 2024

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Immunomodulating Agents
• Other Study ID Numbers: 2022-YJXBF-03-01

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