Clinical trial NCT04612712: A Phase 1/2 Study of Donafenib in Combination With KN046 in Advanced Gastrointestinal Tumors
Official title: A Phase 1/2 Dose Escalation and Expansion Study of Donafenib Tosilate Tablets in Combination With KN046 Injection in Advanced Gastrointestinal Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Advanced Gastrointestinal Tumors
Lead sponsor: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
Sponsor class: INDUSTRY
Collaborators: name: Jiangsu Alphamab Biopharmaceuticals Co., Ltd
First posted: 2020-11-03
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Phase I part - Tolerability of Donafenib in Combination With KN046
timeFrame: 21 days after the first dose of Donafenib and KN046
measure: Phase II part - Objective response rate(ORR)
timeFrame: 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]
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: Through study completion, an expected average of 3 year
measure: Progression-Free Survival (PFS)
timeFrame: Through study completion, an expected average of 3 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital Affiliated to Fudan University
Study officials:
affiliation: Shanghai Zhongshan Hospital
name: Tianshu Liu, PhD
role: STUDY_CHAIR
References: