Clinical trial
A Phase 1/2 Dose Escalation and Expansion Study of Donafenib Tosilate Tablets in Combination With KN046 Injection in Advanced Gastrointestinal Tumors
Name
KN046D-C-101
Description
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.
Trial arms
Trial start
2021-01-19
Estimated PCD
2023-12-01
Trial end
2023-12-01
Status
Recruiting
Phase
Early phase I
Treatment
Donafenib Tosilate Tablets
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.
Arms:
Donafenib+ KN046
KN046 Injection
5mg/kg Q3W
Arms:
Donafenib+ KN046
Size
42
Primary endpoint
Phase I part - Tolerability of Donafenib in Combination With KN046
21 days after the first dose of Donafenib and KN046
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]
Eligibility criteria
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.
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 42, 'type': 'ESTIMATED'}}
Updated at
2022-11-29
1 organization
2 products
1 indication
Organization
Suzhou Zelgen BiopharmaceuticalsProduct
DonafenibIndication
Advanced Gastrointestinal TumorsProduct
KN046