An Evaluation of the Effectiveness and Safety of Decitabine Combined With TQB2450 Injection (PD-L1 Monoclonal Antibody) or Decitabine + Anlotinib Combined With TQB2450 Injection in the Treatment of PD-1 Monoclonal Antibody-resistant Digestive System Tumors I /Phase II Clinical Study
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 60
- 主要终点
- Overall response rate (ORR)
研究概览
简要总结
This clinical study focused on patients with digestive system tumors resistant to PD-1 inhibitors, and explored the reversal resistance of epigenetic drugs (decitabine) and TKI drugs (anlotinib) in this part of patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary participation and written informed consent;
- •Age: 18-70 years old;
- •No gender limitation;
- •Digestive system malignant tumor diagnosed by pathology;
- •Previously received PD-1 monoclonal antibody Or the combination therapy fails;
- •There is at least one measurable lesion (according to the RECIST1.1 standard) or an unmeasurable lesion that can be evaluated, and the imaging diagnosis is ≤21 days from the selection time；
- •The expected survival period is ≥3 months;
- •General physical status (ECOG) 0-1;
- •Sufficient bone marrow hematopoietic function (within 7 days); normal liver and kidney function (within 14 days)；
- •Heart, lung, kidney, and liver functions are generally normal.
排除标准
- •People who are currently receiving other effective treatments;
- •Patients who have been treated with anti-vascular TKI drugs in the past;
- •Patients who have participated in other clinical trials within 4 weeks before enrollment;
- •Allergic to study drugs;
- •Those without measurable tumor lesions, such as body cavity effusion or diffuse infiltration of organs;
- •Those with measurable lesions that have received radiotherapy.
- •Patients with other primary malignant tumors other than digestive system tumors at the same time, except for early solid tumors that have been cured for more than 1 year;
- •Clinically significant cardiovascular diseases, such as heart failure (NYHAIII-IV), are not controlled A history of coronary heart disease, cardiomyopathy, arrhythmia, uncontrolled hypertension or myocardial infarction within the past 1 year;
- •Neurological or mental disorders that affect cognitive ability, including central nervous system metastasis;
- •Existed within 14 days before enrollment Active severe clinical infections (>grade 2 NCI-CTCAE version 5.0), including active tuberculosis;
- •Known or self-reported HIV infection or active hepatitis B or C;
- •Uncontrolled Systemic diseases, such as poorly controlled diabetes;
- •A history of interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis, or evidence of interstitial lung disease on baseline chest X-ray/CT;
- •Keratitis , Ulcerative keratitis or severe dry eye;
- •Known hypersensitivity or allergic reaction to any component of the study drug;
- •Pregnancy (determined by serum β-chorionic gonadotropin test) or breast-feeding.
研究组 & 干预措施
decitabine＋ TQB2450 injection (PD-L1 monoclonal antibody)
Decitabine (10mg ivgttqd, d1-5) combined with TQB2450 injection (1200mg ivgtt, d5)
干预措施: decitabine＋ TQB2450 injection (Drug)
decitabine + anlotinib ＋ TQB2450 injection (PD-L1 monoclonal antibody)
Decitabine and Anlotinib (decitabine 10mg ivgtt qd, d1-5; Anlotinib 8mg po.qd, d5-18) combined with TQB2450 injection (1200mg ivgtt, d5), using the traditional 3+3 experimental design (First enroll 3 subjects. If 1 case of DLT is observed, 3 more subjects need to be added to the same dose group to further evaluate the toxicity) to observe DLT to evaluate MTD. The trial starts from the 8mg dose of Anlotinib Start.
干预措施: decitabine＋ TQB2450 injection＋Anlotinib (Drug)
结局指标
主要结局
Overall response rate (ORR)
时间窗: up to 48 weeks
Objective response rate refers to the percentage of complete (CR) or partial response (PR) subjects determined by the investigator based on RECIST 1.1 or iRECIST (CR under iRECIST criteria, PR can occur after imaging disease progression).
次要结局
- Overall survival (OS)(up to 48 weeks)
研究者
Shen Lin
Professor
Peking University