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

Phase 1

Recruiting

• Conditions: Advanced Gastrointestinal Tumors
• Interventions: Drug: Donafenib Tosilate Tablets; Biological: KN046 Injection

• Registration Number: NCT04612712
• Lead Sponsor: Suzhou Zelgen Biopharmaceuticals Co.,Ltd

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.

Study Timeline

• Study First Submitted: 2020-10-29
• Study First Submitted QC: 2020-10-29
• Study First Posted: 2020-11-03
• Study Start: 2021-01-19
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-28
• Last Update Posted: 2022-11-29
• Primary Completion: 2023-12
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 42

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Donafenib+ KN046	Donafenib Tosilate Tablets	Donafenib 50mg BID/100 mg BID/200 mg BID orally + KN046 5mg/kg Q3W iv
Donafenib+ KN046	KN046 Injection	Donafenib 50mg BID/100 mg BID/200 mg BID orally + KN046 5mg/kg Q3W iv

Primary Outcome Measures

Name	Time	Method
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).
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).

Secondary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Zhongshan Hospital Affiliated to Fudan University; 🇨🇳 Shanghai, China