NCT05394233Unknown2 期
Efficacy and Safety of Tislelizumab Combined With Bevacizumab and Platinum Plus Pemetrexed for Untreated EGFR+ and High PD-L1 Expression Non-squamous NSCLC :a Phase II, Single-center, Single Arm Study
Sichuan Cancer Hospital and Research Institute1 个研究点 分布在 1 个国家目标入组 20 人开始时间: 2022年6月1日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- middle progression free survival
研究概览
简要总结
A study to evaluate the efficacy and safety of tislelizumab combined with bevacizumab and platinum-based pemetrexed in the treatment of naïve patients with advanced non-squamous non-small cell lung cancer with sensitive EGFR mutations and high PD-L1 expression Prospective, open-label, single-arm phase II clinical study
详细描述
A study to evaluate the efficacy and safety of tislelizumab combined with bevacizumab and platinum-based pemetrexed in the treatment of naïve patients with advanced non-squamous non-small cell lung cancer with sensitive EGFR mutations and high PD-L1 expression Prospective, open-label, single-arm phase II clinical study;
Research purposes:
Main purpose: To evaluate the median progression-free rate of tislelizumab combined with bevacizumab and platinum pemetrexed in treatment-naïve advanced non-small cell lung cancer patients with sensitive EGFR mutations and high PD-L1 expression Survival (middle progression free survival, mPFS)
Secondary purpose:
- Evaluation of objective response rate (ORR) according to RECIST version 1.1;
- Evaluation of disease control rate (DCR) according to RECIST version 1.1;
- Assess overall survival (OS);
- Assess Duration of Response (DOR);
- Evaluate the safety of the treatment using NCI-CTCAE v5;
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 18 and ≤ 75 years of age. Signed the informed consent form prior to patient entry
- •Histologically or pathologically confirmed non-squamous non-small cell lung cancer(NSCLC) with stage IV /III
- •Patients with EGFR sensitive mutations: 19del and L858R who have not been treated with TKI for the first time, the patients need to provide the test results of the certified detection platform, and the PD-L1 expression based on tissue specimen detection is greater than 50% (PD-L1 detection clone number: SP263).
- •A World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) Performance Status Score (PS) of 0 or 1 at the time of recruitment.
- •Adequate organ and bone marrow function, defined as:
- •Hemoglobin≥9.0 g/dL
- •Absolute neutrophil count ≥1.5 × 109/L
- •Platelet count ≥100 × 109/L
- •Serum bilirubin ≤ 1.5 × upper limit of normal range (ULN). This does not apply to patients diagnosed with Gilbert's syndrome (persistent or recurrent hyperbilirubinemia [primarily unconjugated bilirubin] without evidence of hemolysis or liver pathology), which may be allowed after consultation with a physician patients participating in the study.
- •ALT and AST ≤2.5 × ULN
- •Measured creatinine clearance (CL) >40 mL/min or Cockcroft-Gault calculated CL >40 mL/min (using actual body weight) Men: Creatinine clearance (mLmin⁄) = body weight (kg) x (140-age) 72 x serum creatinine (mg/dL) Female: creatinine clearance (mLmin⁄) = body weight (kg) x (140-age) 72 x serum creatinine (mg/dL) x 0.85
- •The expected survival time of patients is ≥3 months
- •Weight > 30 kg
- •Have the ability to sign the informed consent form and comply with the requirements and restrictions listed in the informed consent form (ICF) and this protocol.
排除标准
- •Patients with grade ≥2 non-infectious pneumonia.
- •History of allogeneic organ transplantation, except corneal transplantation.
- •Active or previously documented autoimmune or inflammatory diseases (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [except diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatous vasculitis, Graves disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). Exceptions to this standard include:
- •Vitiligo or alopecia patients
- •Patients with hypothyroidism who are stable on hormone replacement therapy (eg, after Hashimoto's syndrome)
- •Any chronic skin disease that does not require systemic treatment
- •Patients without active disease within the past 5 years may be included in the study, but only after consultation with the study physician
- •Patients with celiac disease that can be controlled with diet alone
- •Uncontrolled concurrent diseases, including but not limited to: persistent or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled arrhythmia, active ILD , Severe chronic gastrointestinal disease with diarrhea, or a psychiatric/social condition that may limit compliance with study requirements, cause a significantly increased risk of AEs, or interfere with the subject's ability to provide written informed consent.
- •History of another primary malignant tumor, except for the following cases;
- •Malignant tumors with low potential risk of recurrence and no known active disease ≥5 years prior to first dose treated with curative intent
- •Adequately treated non-melanoma skin cancer with no evidence of disease or lentigo maligna
- •Adequately treated cervical carcinoma in situ without evidence of disease
- •History of active primary immunodeficiency
- •Active infection, including tuberculosis (clinical assessment, including clinical history, physical examination, radiographic findings, and tuberculosis testing consistent with local clinical practice).
- •Known history of human immunodeficiency virus (HIV) infection; known active syphilis infection.
- •Untreated active hepatitis B
- •Hepatitis B patients who meet the following criteria are eligible for inclusion:
- •Hepatitis B virus (HBV) load was below the lower limit of detection in our hospital before the first dose, and received anti-HBV therapy throughout the study period to avoid viral reactivation.
- •Subjects with active hepatitis C (HCV) infection, HCV antibody positive patients only meet the study inclusion criteria when the polymerase chain reaction of HCV RNA is negative.
- •Active brain metastases or spinal cord compression. Prior to study entry, all patients underwent MRI (preferred) or CT examination, preferably brain examination with intravenous contrast.
- •Known allergy or hypersensitivity reaction to any study drug or any study drug excipients
- •Previous exposure to immune-mediated therapy, including but not limited to: anti-PD-1, anti-PD-L1 and anti-programmed death ligand 2 (anti-PD-L2) antibodies, except for therapeutic anti-tumor vaccines .
- •Live attenuated vaccine should be vaccinated within 30 days before the first dose, and live vaccine should not be vaccinated within 30 days after the last dose.
- •Major surgery (as defined by the investigator) within 42 days prior to the first dose.
- •Within 14 days before administration, immunosuppressive drugs are being used or have been used in the past. Exceptions to this standard include:
- •Intranasal, inhaled, topical steroids, or topical steroid injections (eg, intra-articular injections)
- •Systemic corticosteroid therapy not exceeding 10 mg/day of prednisone or its physiologic equivalent
- •Steroids administered as prophylactic for hypersensitivity reactions (eg, prophylactic administration of CT scan)
- •Pregnant or lactating female patients and fertile male or female patients are unwilling to take effective contraceptive measures from screening to 6 months after the last dose.
- •Other researchers think that it is not suitable for inclusion.
- •Mixed cell lung cancer: non-small cell and small cell mixed lung cancer and mixed adenosquamous lung cancer dominated by squamous cell carcinoma.
- •Non-squamous non-small cell lung cancer with hemoptysis (>50 ml/day); clinically significant hemoptysis or bleeding symptoms occurred within 3 months before enrollment.
- •Patients with brain metastases whose symptoms are not controlled after treatment.
- •Imaging (CT/MRI) shows that the tumor lesion is less than 5 mm away from the large blood vessels, there is a central tumor that invades the local large blood vessels and is less than 2 cm away from the bronchial tree; or there is an obvious lung cavity or necrotic tumor.
- •Arterial/venous thrombotic events that occurred within 12 months before enrollment
- •Patients with any severe and/or uncontrolled disease (hypertension, liver cirrhosis, heart failure, etc.)
- •Major surgical operation or severe traumatic injury, fracture or ulcer occurred within 4 weeks before enrollment
- •Severe weight loss (greater than 10%)
- •Abnormal coagulation function, with bleeding tendency or receiving thrombolytic or anticoagulation therapy
研究组 & 干预措施
tislelizumab combined with bevacizumab and platinum plus pemetrexed
Experimental
Drug:
Induction Phase:
Bevacizumab: 7.5 mg/kg administered as an IV infusion on Day 1 of each 3-week cycle for 4 cycles Cisplatin 75 mg/m2 will be administered as an intravenous infusion over 2 hours every 3 weeks for 4 cycles.
Pemetrexed, 500 mg/m2, intravenously, every 3 weeks for 4 cycles
Maintenance phase:
Tislelizumab, 200 mg IV every 3 weeks;until disease progression or intolerance Bevacizumab: 7.5 mg/kg administered as an intravenous infusion on Day 1 of each 3-week cycle;until disease progression or intolerance
干预措施: Tislelizumab Combined With Bevacizumab and Platinum Plus Pemetrexed (Drug)
结局指标
主要结局
middle progression free survival
时间窗: Estimated about 6 months
To evaluate the median progression-free survival (middle) of tislelizumab combined with bevacizumab and platinum-based pemetrexed in treatment-naïve advanced non-small cell lung cancer patients with sensitive EGFR mutations and high PD-L1 expression. progression free survival (mPFS)
次要结局
未报告次要终点
研究者
Juan LI, MD
Director of standard treatment department of medical oncology
Sichuan Cancer Hospital and Research Institute
研究点 (1)
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