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

Primary Purpose

Advanced Gastrointestinal Tumors

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Donafenib Tosilate Tablets
KN046 Injection
Sponsored by
Suzhou Zelgen Biopharmaceuticals Co.,Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Gastrointestinal Tumors

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Zhongshan Hospital Affiliated to Fudan UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Donafenib+ KN046

Arm Description

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

Outcomes

Primary Outcome Measures

Phase I part - Tolerability of Donafenib in Combination With KN046
Evaluated by severity of drug-related adverse events (AEs), serious adverse events (SAEs).
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).

Secondary Outcome Measures

Duration of Response (DOR)
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)
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.

Full Information

First Posted
October 29, 2020
Last Updated
November 28, 2022
Sponsor
Suzhou Zelgen Biopharmaceuticals Co.,Ltd
Collaborators
Jiangsu Alphamab Biopharmaceuticals Co., Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT04612712
Brief Title
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

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 19, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Suzhou Zelgen Biopharmaceuticals Co.,Ltd
Collaborators
Jiangsu Alphamab Biopharmaceuticals Co., Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Gastrointestinal Tumors

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Donafenib+ KN046
Arm Type
Experimental
Arm Description
Donafenib 50mg BID/100 mg BID/200 mg BID orally + KN046 5mg/kg Q3W iv
Intervention Type
Drug
Intervention Name(s)
Donafenib Tosilate Tablets
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
KN046 Injection
Intervention Description
5mg/kg Q3W
Primary Outcome Measure Information:
Title
Phase I part - Tolerability of Donafenib in Combination With KN046
Description
Evaluated by severity of drug-related adverse events (AEs), serious adverse events (SAEs).
Time Frame
21 days after the first dose of Donafenib and KN046
Title
Phase II part - Objective response rate(ORR)
Description
Objective response rate based on the RECIST 1.1 by investigator. Percentage of subjects achieving complete response (CR) and partial response (PR).
Time Frame
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 Outcome Measure Information:
Title
Duration of Response (DOR)
Description
It is defined as time between the date of first radiographic documented objective response and the date of the radiographic documented disease progression.
Time Frame
Through study completion, an expected average of 3 year
Title
Progression-Free Survival (PFS)
Description
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.
Time Frame
Through study completion, an expected average of 3 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tianshu Liu, PhD
Phone
021-64041990
Email
Liu.tianshu@zs-hospital.sh.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tianshu Liu, PhD
Organizational Affiliation
Shanghai Zhongshan Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Zhongshan Hospital Affiliated to Fudan University
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tianshu Liu
Phone
02164041990
Email
Liu.tianshu@zs-hospital.sh.cn

12. IPD Sharing Statement

Plan to Share IPD
No

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

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