A Randomized Controlled Study Comparing the Efficacy of QL1706 Combined With Chemotherapy in the Treatment of Immune-mediated Non-small Cell Lung Cancer
概览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Anhui Provincial Cancer Hospital
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- PFS
概览
简要总结
Lung cancer is the leading cause of cancer-related deaths worldwide. According to the 2023 global cancer statistics, there are approximately 2.47 million new cases and 1.76 million deaths of lung cancer annually, accounting for 18.4% of all cancer deaths. Among them, driver gene negative NSCLC accounts for about 30% -40% of all NSCLC. In China, the incidence rate and mortality of lung cancer rank first. In 2022, there will be about 870000 new cases and 760000 deaths. In Chinese NSCLC patients, the EGFR mutation rate is about 50%, ALK fusion is about 5%, other mutations (ROS1, RET, etc.) are about 5% -10%, and the negative proportion of driver genes is about 30% -40%. Traditional treatment for late stage non-small cell lung cancer with negative driver genes has limited clinical efficacy. In recent years, the emergence of immune checkpoint inhibitors (ICIs) has greatly changed the treatment pattern of advanced non-small cell lung cancer patients, significantly prolonging the overall survival of advanced cancer patients. For the follow-up treatment of patients with previous immunotherapy, the current standard treatment regimen is still mainly chemotherapy. However, these plans have mediocre efficacy and significant side effects, making it difficult to meet the current clinical treatment needs. At present, there is no unified treatment plan for first-line immunotherapy or immunotherapy combined with chemotherapy in patients with driver gene negative advanced NSCLC. Second line chemotherapy such as docetaxel is currently recommended as the standard treatment plan in NCCN guidelines and CSCO guidelines. Research suggests that for patients with first-line immune resistance or immune combined chemotherapy resistance, second-line immune re challenge can still bring certain survival benefits to patients, but the benefits are limited and new treatment options need to be explored.
Iparomlimab injection (drug number QL-1706) is a novel combination antibody independently developed by Qilu Company. It consists of Iparomlimab, an IgG4 antibody targeting PD-1, and Tuvonralimab, an IgG1 antibody targeting CTLA-4, in a fixed ratio. It has a synergistic mechanism of simultaneously blocking PD-1 and CTLA-4. In summary, ICIs are still an important treatment strategy for advanced non-small cell lung cancer. However, the emergence of drug resistance after immunotherapy seriously affects the survival time and prognosis of patients. Preliminary research has been conducted on the resistance mechanism of immunotherapy, but more research is needed to clarify the main mechanisms of action, in order to further prevent and overcome drug resistance. QL1706 has shown promising preliminary efficacy and good tolerability in PD-1 resistant NSCLC in preclinical and phase I clinical studies. Based on this, this study aims to conduct an exploratory study on QL1706 combined with chemotherapy compared to chemotherapy alone in the treatment of immune regulated non-small cell lung cancer with negative driver genes.
详细描述
This study is a prospective, multicenter, open label randomized controlled trial design, recruiting 96 immunocompromised driver gene negative patients with locally advanced or recurrent/metastatic non-small cell lung cancer. The experimental group received QL1706 combined with docetaxel or gemcitabine treatment in a 1:1 ratio, while the control group received docetaxel or gemcitabine treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Voluntarily participate in the research and sign an informed consent form; Age ≥ 18 years old, ≤ 75 years old;
- •Diagnosed with NSCLC through histology or cytology;
- •No EGFR sensitive mutations or ALK gene translocation changes;
- •Previously received PD-1/PD-L1 inhibitors combined with platinum based dual therapy or sequential therapy as first-line treatment for advanced metastatic or recurrent NSCLC, and disease progression occurred during or after treatment; At least one measurable lesion should be used as the target lesion (RECIST v1.1 standard);
- •ECOG score: 0-2 points;
- •Expected survival period is not less than 12 weeks;
- •Women of childbearing age must undergo a pregnancy test (serum or urine) with a negative result within 28 days before enrollment, and voluntarily use appropriate contraception methods during the observation period and within 8 weeks after the last dose; For males, surgical sterilization or consent to use appropriate contraception methods during the observation period and within 8 weeks after the last dose should be provided;
- •The laboratory test results during the screening period indicate that the patient has good organ function: a) Hematology (no blood transfusion within 14 days and no treatment with blood components or granulocyte colony-factor): Neutrophil count (NEU) ≥ 1.5 × 10 \^ 9/L (1500/mm3); Platelet count (PLT) ≥ 100 × 10 \^ 9/L (100000/mm3); Hemoglobin ≥ 90 g/L; b) Liver: serum total bilirubin (TBil) ≤ ULN; Glutamate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 × ULN; AST or ALT should be 1.5-3.5 × ULN, and alkaline phosphatase (ALP) should be ≤ 2.5 × ULN; c) Kidney: creatinine clearance rate (CrCl) calculated value ≥ 30 mL/min; d) Coagulation function: International normalized ratio (INR) ≤ 1.5, and prothrombin time (PT) or activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; j) International Normalized Ratio (INR) ≤ 1.5; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN;
- •Patients whom researchers believe can benefit.
排除标准
- •There are EGFR sensitive mutations or ALK gene translocation changes present;
- •Previously received PD1/CTLA4 bispecific antibody therapy;
- •Adverse reactions caused by previous treatment have not recovered to CTCAE (version 5.0) grade 1 or below (excluding toxicity ≤ grade 2 that has been determined by the researcher to exist for a long time, cannot be recovered, and does not increase safety risks);
- •Symptomatic central nervous system metastasis. Patients who have received treatment for brain metastases and have been deemed stable by researchers may consider participating in this study;
- •For patients with poor control of cancer-related pain, those who require analgesic treatment must receive a stable dose of treatment before participating in the study;
- •Chest fluid, ascites or pericardial effusion with clinical symptoms or unstable condition after symptomatic treatment;
- •Known to have a history of severe allergic reactions to the drug and its components, planned chemotherapy drugs, and those with a history of severe allergic reactions;
- •Suffering from or suspected of active autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory intestinal diseases, etc., except: type I diabetes and hypothyroidism that can be controlled through stable dose replacement treatment, and skin diseases that do not require systemic treatment (such as psoriasis, vitiligo);
- •History of interstitial lung disease or drug-induced interstitial lung disease or pneumonia in the past;
- •Corticosteroid drugs (prednisone\>10mg/day or equivalent dose) or other immunosuppressive drugs received systemically within 14 days prior to the first study medication;
研究组 & 干预措施
QL1706 combined with chemotherapy
QL1706：5mg/kg，iv，d1 combined with Gemcitabine (1000mg/m2，iv，d1、d8 )or DOCETAXEL (60mg/m2，iv，d1)
干预措施: QL1706 combined with Chemotherapy (Drug)
chemotherapy
Gemcitabine (1000mg/m2，iv，d1、d8 )or DOCETAXEL (60mg/m2，iv，d1)
干预措施: Chemotherapy (Drug)
结局指标
主要结局
PFS
时间窗: "From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months"
Refers to the time from the start of medication to the first occurrence of disease progression or death from any cause
次要结局
- ORR(through study completion, an average of 1 year)
- OS(through study completion, an average of 1 year)
- DCR(through study completion, an average of 1 year)
- DOR(through study completion, an average of 1 year)
- AE(through study completion, an average of 1 year)
研究者
Shuanghu Yuan
Professor
Anhui Provincial Cancer Hospital