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

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.