A Phase 1/2 Dose Escalation and Expansion Study of Donafenib Tosilate Tablets in Combination With KN046 Injection in Advanced Gastrointestinal Tumors
概览
- 阶段
- 1 期
- 干预措施
- KN046 Injection
- 疾病 / 适应症
- Advanced Gastrointestinal Tumors
- 发起方
- Suzhou Zelgen Biopharmaceuticals Co.,Ltd
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Phase I part - Tolerability of Donafenib in Combination With KN046
- 状态
- 终止
- 最后更新
- 昨天
概览
简要总结
This study is an open, multi-center clinical trial, the purpose is to study the safety and preliminary efficacy of Donafenib combined with KN046 in subjects with Advanced Gastrointestinal Tumors.
详细描述
The study consists of dose escalation and dose expansion. The preset dose of Donafenib is 50 mg BID, 100 mg BID and 200 mg BID, and the preset dose of KN046 is 5 mg/kg Q3W. Dose expansion will enroll subjects who with advanced hepatocellular carcinoma.
研究者
入排标准
入选标准
- •Male or female aged 18-70 years;
- •Phase I dose escalation: Advanced gastric cancer, esophageal cancer, colorectal cancer, hepatocellular carcinoma, pancreatic cancer (other than pancreatic neuroendocrine tumors) and intrahepatic cholangiocarcinoma that failed standard treatments confirmed by histopathology and/or cytology; Among them, the Child-Pugh score of liver function in patients with hepatocellular carcinoma is less than 5,
- •Phase II advanced hepatocellular carcinoma Dose expansion: Patients with advanced hepatocellular carcinoma who are clinically diagnosed or confirmed by histopathology and/or cytology and are not suitable for surgical resection; The patient has not undergone first-line systemic treatment \[small molecule targeted drugs (such as sorafenib, lenvatinib, etc.), systemic chemotherapy\] and tumor immunotherapy (anti-PD-1/L1, CTLA-4, etc.); Child-Pugh score of liver function ≤ 6;
- •Has at least one measurable lesion based on RECIST 1.1;
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
- •Life expectancy ≥12 weeks;
- •Patients must be able to understand and willing to sign a written informed consent document.
排除标准
- •Subjects who have previously received immune checkpoint inhibitors (such as anti-PD-1/L1, CTLA-4, etc.);
- •History of interstitial lung disease or non-infectious pneumonia;
- •Clinically obvious gastrointestinal abnormalities, which may affect the intake, transport or absorption of drugs (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.), or patients undergoing total gastrectomy;
- •Has received vaccination within 4 weeks prior to the first dose.
- •Has participated in other anticancer drug clinical trials within 4 weeks.
- •According to the judgement of the investigators, there are other factors that subjects are not suitable for the study.
研究组 & 干预措施
Donafenib+ KN046
Donafenib 50mg BID/100 mg BID/200 mg BID orally + KN046 5mg/kg Q3W iv
干预措施: KN046 Injection
Donafenib+ KN046
Donafenib 50mg BID/100 mg BID/200 mg BID orally + KN046 5mg/kg Q3W iv
干预措施: Donafenib Tosilate Tablets
结局指标
主要结局
Phase I part - Tolerability of Donafenib in Combination With KN046
时间窗: 21 days after the first dose of Donafenib and KN046
Evaluated by severity of drug-related adverse events (AEs), serious adverse events (SAEs).
Phase II part - Objective response rate(ORR)
时间窗: From the time of initial administration until intolerant toxicity, disease progression, withdrawal of ICF, loss of follow-up, death or early study termination occurs (whichever occurs first),assessed up to 36 months]
Objective response rate based on the RECIST 1.1 by investigator. Percentage of subjects achieving complete response (CR) and partial response (PR).
次要结局
- Duration of Response (DOR)(Through study completion, an expected average of 3 year)
- Progression-Free Survival (PFS)(Through study completion, an expected average of 3 year)