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

NCT04612712 | Terminated Phase 1

• 1 other identifier: KN046D-C-101
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Gastrointestinal Tumors

Outcome Measures

Primary Outcomes (2)

• Phase I part - Tolerability of Donafenib in Combination With KN046

  Evaluated by severity of drug-related adverse events (AEs), serious adverse events (SAEs).

  21 days after the first dose of Donafenib and KN046

• Phase II part - Objective response rate(ORR)

  Objective response rate based on the RECIST 1.1 by investigator. Percentage of subjects achieving complete response (CR) and partial response (PR).

  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 (2)

• Duration of Response (DOR)

  Through study completion, an expected average of 3 year

• Progression-Free Survival (PFS)

  Through study completion, an expected average of 3 year

Study Arms (1)

Donafenib+ KN046

EXPERIMENTAL

Donafenib 50mg BID/100 mg BID/200 mg BID orally + KN046 5mg/kg Q3W iv

Drug: Donafenib Tosilate Tablets; Biological: KN046 Injection

Interventions

Donafenib Tosilate Tablets DRUG

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.

Donafenib+ KN046

KN046 Injection BIOLOGICAL

5mg/kg Q3W

Donafenib+ KN046

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jiangsu Alphamab Biopharmaceuticals Co., Ltd: collaborator
• Suzhou Zelgen Biopharmaceuticals Co.,Ltd: lead

Study Sites (1)

Zhongshan Hospital Affiliated to Fudan University

Shanghai, China

Location

Study Officials

• Tianshu Liu, PhD

  Shanghai Zhongshan Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2020
• First Posted: November 3, 2020
• Study Start: January 19, 2021
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: May 1, 2026

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)