Efficacy and Safety of Pembrolizumab as First-line Treatment for Advanced Non-small Cell Lung Cancer Complicated With Chronic Obstructive Pulmonary Disease: a Prospective, Single-arm, Single-center Phase II Trial
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- NSCLC With COPD
- Sponsor
- Tianjin Chest Hospital
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- PFS
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This clinical trial aims to evaluate the efficacy and safety of pembrolizumab in the first-line treatment of advanced NSCLC complicated with COPD and its influence on the course of COPD, so as to provide prospective clinical evidence for immunotherapy of NSCLC complicated with COPD in China and to guide clinical application.
Detailed Description
This clinical study mainly includes 3 stages of screening, treatment and follow-up. Pabolivizumab at a fixed dose of 200 mg intravenous infusion on day 1 for Q3W, continued to maintain administration for no more than 35 cycles, or until the imaging proves the early termination of PD or other protocols. Imaging evaluation is performed every 6 weeks within 6 months from the first dose of pabolizumab and approximately every 12 weeks thereafter until disease progression or early withdrawal. Conduct regular safety assessments, document changes in COPD condition, track adverse events until remission or stabilization, or restore baseline levels, or receive other anti-tumor therapy; Record the combined medications. Main research objectives:Evaluation of PFS in patients with advanced NSCLC and COPD treatment of pabolivizumab. Secondary research objectives:To assess the ORR and acute exacerbation rate (times/person/year) and adverse reactions of PABLIZUMAB in patients with advanced NSCLC with COPD. Purpose of exploratory research:The expression levels of PD-L1, CD4+ and CD8+ T lymphocytes in tumor tissues of patients with NSCLC and COPD before treatment were laboratory tested, and the correlation between different COPD grades and immune cell infiltration and efficacy was explored. This study was designed as a single-armed, single-center, prospective, phase II clinical study with 30 clinical, radiographic, pulmonary function and pathologically confirmed advanced (stage IV) NSCLC combined with COPD primary treatment subjects.
Investigators
Jianwen Qin
chief physicians
Tianjin Chest Hospital
Eligibility Criteria
Inclusion Criteria
- •Signed written informed consent before enrollment;
- •Men and women aged 18-75;
- •The patient must be able to provide fresh or archived tumor tissue and its pathology report;
- •No previous antitumor therapy, life expectancy is not less than 12 weeks;
- •Newly diagnosed NSCLC subjects confirmed by pathology and imaging; Stage: cT1-4N1-3M1 (stage Ⅳ), AJCC eighth edition clinical staging of lung cancer;
- •Asymptomatic patients with NSCLC brain metastases
- •PD-L1 tumor fraction (TPS) ≥1%;
- •Epidermal growth factor receptor (EGFR) gene mutation negative and anaplastic lymphoma kinase (ALK) negative;
- •Measurable lesions that meet RECIST v1.1 criteria;
- •Patients with COPD who met the relevant diagnostic criteria for COPD in the Guidelines for the Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease (Revised 2021) formulated by Chinese Society of Respiratory Medicine, and whose condition was stable for ≥2 weeks;
Exclusion Criteria
- •Previous radiotherapy, chemotherapy, long-term or high-dose hormone therapy, surgery, or molecular targeted therapy;
- •The subject has previous or concurrent other malignant tumors;
- •History of asthma or other respiratory diseases (bronchiectasis, tuberculosis, interstitial pneumonia, occupational lung disease, sarcoidosis, etc.);Patients with objective evidence of radiation pneumonitis, drug-associated pneumonitis, or severe impairment of pulmonary function;
- •History of lobectomy;
- •A history of clinically significant circulatory failure;
- •Significant contraindications for spirometry (history of myocardial infarction, cerebral artery or aortic aneurysm, history of eye surgery, hemoptysis);
- •Patients with rheumatic diseases;Patients with heart, cerebrovascular, liver, kidney, hematopoietic system and other serious primary diseases.
- •Patients with a history of acute gastrointestinal bleeding within 3 months;
- •Previous immune checkpoint inhibitor therapy;The subject is known to have a previous allergy to macromolecular protein preparations, or to any PD-1 mab component;
- •The subject has any active autoimmune disease or a history of autoimmune disease (e.g., but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism;Subjects with vitiligo or complete remission of asthma in childhood without any intervention as adults were included;Subjects with asthma requiring medical intervention with bronchodilators were excluded);
Arms & Interventions
treatment group
All patients who met the inclusion criteria and did not meet the exclusion criteria were enrolled in the treatment group
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
PFS
Time Frame: 30 months
The time from the beginning of randomization to the progression of tumor development or death for any reason.
Secondary Outcomes
- ORR(12 months)
- adverse events(30 months)
- Rate of acute exacerbations of COPD (times/year)(30 months)