A Phase 1/2 Study of Donafenib in Combination With KN046 in Advanced Gastrointestinal Tumors

A Phase 1/2 Dose Escalation and Expansion Study of Donafenib Tosilate Tablets in Combination With KN046 Injection in Advanced Gastrointestinal Tumors

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.

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.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.