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

NCT06613308 | Not Yet Recruiting

• 1 other identifier: 2022-YJXBF-03-01
• Study Type: observational
• Target: 20
• Locations: 0 countries
• Sites: N/A

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）

Conditions

Lung Cancer (NSCLC)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Pathologic complete response (pCR)

  Whithin time from enrollment to surgery

• Disease free survival (DFS)

  Whithin 1 year after surgery

• Overall survival (OS)

  Whithin 1 year after enrollment

• Immune-related adverse event (irAE)

  Whithin 1 year after enrollment

• Changes in microbiomics in respiratory tract and gut

  Whithin 1 year after enrollment

Study Arms (2)

Arm1(Neoadjuvant immunotherapy combined with chemotherapy)

Drug: Neoadjuvant immunotherapy combined with chemotherapy

Arm2(Neoadjuvant chemotherapy)

Drug: Neoadjuvant chemotherapy

Interventions

Neoadjuvant immunotherapy combined with chemotherapy DRUG

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.

Arm1(Neoadjuvant immunotherapy combined with chemotherapy)

Neoadjuvant chemotherapy DRUG

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.

Arm2(Neoadjuvant chemotherapy)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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).

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Capital Medical University: lead
• China-Japan Friendship Hospital: collaborator

Biospecimen

Retention: SAMPLES WITH DNA

Microbiome in faeces, sputum, swabs, BALF, surgically resected lung lesions

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Drug Therapy; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics; Combined Modality Therapy

Study Officials

• science and technology center

  China-Japan Friendship Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yeming Wang, M.D.

CONTACT

+86 84206264; wwyymm_love@163.com

Dong Liu, M.D.

CONTACT

liudongdoc@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: September 15, 2024
• First Posted: September 25, 2024
• Study Start: September 25, 2024
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: September 25, 2024

Record last verified: 2024-08