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

Not yet recruiting

• Conditions: Lung Cancer (NSCLC)
• Interventions: Drug: Neoadjuvant immunotherapy combined with chemotherapy; Drug: Neoadjuvant chemotherapy

• Registration Number: NCT06613308
• Lead Sponsor: Capital Medical University

Brief Summary

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）

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-08
• Study First Submitted: 2024-09-15
• Study First Submitted QC: 2024-09-23
• Last Update Submitted: 2024-09-23
• Study Start: 2024-09-25
• Study First Posted: 2024-09-25
• Last Update Posted: 2024-09-25
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Arm1(Neoadjuvant immunotherapy combined with chemotherapy)	Neoadjuvant immunotherapy combined with chemotherapy	-
Arm2(Neoadjuvant chemotherapy)	Neoadjuvant chemotherapy	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Pathologic complete response (pCR)	Whithin time from enrollment to surgery	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).
Disease free survival (DFS)	Whithin 1 year after surgery	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.
Overall survival (OS)	Whithin 1 year after enrollment	defined as time from enrolment to all-cause death
Immune-related adverse event (irAE)	Whithin 1 year after enrollment	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.
Changes in microbiomics in respiratory tract and gut	Whithin 1 year after enrollment	Defined as microbial composition, diversity, and functional activity measured by 16S RNA sequencing
Radiological response	Whithin time from enrollment to surgery	Defined as radiographic change assesed by RECIST 1.1.
Changes in single-cell immune repertoire	Whithin time from enrollment to surgery	Defined as diversity of immune receptors (e.g. TCR and BCR) for T and B cells in lung tissues