Advanced Gastrointestinal Tumors
Conditions
Brief summary
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.
Detailed description
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.
Interventions
In the dose exploration phase (phase I) : three doses of Donafenib tosylate tablets \[50 mg twice a day; 100 mg twice a day; 200 mg twice a day \] will be explored. In the dose expansion phase (phase II), patients with advanced hepatocellular carcinoma will be treated at the recommended dose for phase 2(RP2D).The RP2D will be determined by the dose escalation study.
BIOLOGICALKN046 Injection
5mg/kg Q3W
Sponsors
Suzhou Zelgen Biopharmaceuticals Co.,Ltd
Jiangsu Alphamab Biopharmaceuticals Co., Ltd
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I part - Tolerability of Donafenib in Combination With KN046 | 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) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Through study completion, an expected average of 3 year | It is defined as time between the date of first radiographic documented objective response and the date of the radiographic documented disease progression. |
| Progression-Free Survival (PFS) | Through study completion, an expected average of 3 year | PFS is defined as the time from date of enrollment to the date of the first objectively documented tumor progression or death due to any cause. |
Countries
China
Contacts
STUDY_CHAIRTianshu Liu, PhD
Shanghai Zhongshan Hospital
Outcome results
None listed