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

Официальное название

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

Обзор

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）

Вмешательства

• Препарат 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 thre
• Препарат 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

Первичные конечные точки

• Major pathological response (mPR) [Срок оценки: Whithin time from enrollment to surgery]

Вторичные конечные точки (7)

• Pathologic complete response (pCR) [Срок оценки: Whithin time from enrollment to surgery]
• Disease free survival (DFS) [Срок оценки: Whithin 1 year after surgery]
• Overall survival (OS) [Срок оценки: Whithin 1 year after enrollment]
• Immune-related adverse event (irAE) [Срок оценки: Whithin 1 year after enrollment]
• Changes in microbiomics in respiratory tract and gut [Срок оценки: Whithin 1 year after enrollment]
• Radiological response [Срок оценки: Whithin time from enrollment to surgery]
• Changes in single-cell immune repertoire [Срок оценки: Whithin time from enrollment to surgery]

Критерии участия

Критерии включения

• 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;

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06613308 · 2022-YJXBF-03-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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