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A Phase Ib/II Trial to Evaluate the Safety and Efficacy of QL1706 in Patients With Advanced Hepatocellular Carcinoma

Primary Purpose

Advanced Liver Cancer

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
QL1706
QL1604
Bevacizumab
Sponsored by
Qilu Pharmaceutical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Liver Cancer

Eligibility Criteria

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

Inclusion Criteria: Subjects participated voluntarily and signed an informed consent form. Age ≥ 18 years old at the time of signing the informed consent form, male or female. Advanced hepatocellular carcinoma diagnosed by histopathology or clinical diagnosis, with disease unsuitable for radical surgery and/or local treatment, or disease progression after surgery and/or local treatment. No prior systemic treatment for HCC. Child-Pugh liver function classification of grade A versus better grade B. Eastern Cooperative Oncology Group (ECOG) physical status score of 0-1. Expected survival ≥ 3 months. (9) Functional level of vital organs must be compliant prior to first administration of trial drug. (10) Subject agrees to use effective contraception for contraception from the time of signing the informed consent until 180 days after the last use of the trial drug. Females of childbearing age cannot be in pregnancy or breastfeeding. Exclusion Criteria: Subjects with symptomatic CNS metastases were not allowed to be enrolled. Patients with a history of other malignancies within 5 years prior to signing informed consent. Active autoimmune disease that may have worsened during the course of receiving study drug therapy. Concomitant disease that interferes with the subject's ability to complete the study. History of allogeneic hematopoietic stem cell transplantation or organ transplantation. HIV-positive patients; HCV antibody-positive and HCV RNA-positive patients; patients with co-infection with HBV and HCV. Patients with a known history of psychotropic substance abuse, alcoholism, or drug use Those who have participated in other clinical studies and have used other clinical trial drugs within 4 weeks prior to the use of the trial drug Prior immunotherapy or prior targeted therapy. PCP treatment requires 2 weeks of elution before enrollment and is prohibited during the trial. Known previous hypersensitivity to macromolecular protein agents, or any component of the test drug. Live vaccination within 4 weeks prior to the first administration of the test drug. History of hemoptysis, or history of gastrointestinal bleeding, intestinal obstruction and/or previous clinical signs or symptoms of gastrointestinal obstruction. Abdominal or bronchoesophageal fistula, gastrointestinal perforation or intra-abdominal abscess, major vascular disease. Current or recent treatment with aspirin, clopidogrel, or current or recent treatment with dipyridamole, ticlopidine, and cilostazol; use of anticoagulation therapy for therapeutic purposes

Sites / Locations

  • West China Hospital, Sichuan UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

QL1706(5mg/kg)

QL1604

QL1706(7.5mg/kg)

Arm Description

QL1706(5mg/kg) Combined with Bevacizumab

QL1604 Combined with Bevacizumab

QL1706(7.5mg/kg) Combined with Bevacizumab

Outcomes

Primary Outcome Measures

Objective remission rate (ORR)
The ORR assessed according to RECIST v1.1

Secondary Outcome Measures

Duration of remission (DOR) Duration of remission (DOR) Duration of remission (DOR) Duration of remission (DOR)
The DOR assessed according to RECIST v1.1

Full Information

First Posted
October 21, 2022
Last Updated
November 1, 2022
Sponsor
Qilu Pharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05603039
Brief Title
A Phase Ib/II Trial to Evaluate the Safety and Efficacy of QL1706 in Patients With Advanced Hepatocellular Carcinoma
Official Title
A Phase Ib/II Trial to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of QL1706 or QL1604 Combined With Bevacizumab in Patients With Advanced Hepatocellular Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2021 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
December 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Qilu Pharmaceutical Co., Ltd.

4. Oversight

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

5. Study Description

Brief Summary
This is a phase Ib/II trial to evaluate the safety, pharmacokinetics and preliminary efficacy of QL1706 or QL1604 combined with bevacizumab in patients with advanced hepatocellular carcinoma.
Detailed Description
This is an open, multicenter phase Ib/II trial of QL1706 or QL1604 combined with bevacizumabin patients with advanced hepatocellular carcinoma to evaluate the safety, PK characteristics and preliminary efficacy. This trial is divided into three cohorts, Cohort A, Cohort B and Cohort C. Cohort A was the dose exploration phase of the study, with 2 dose groups designed, QL1706 5mg/kg q3w + bevacizumab 7.5mg/kg q3w group and QL1706 5mg/kg q3w + bevacizumab 15mg/kg q3w group, to explore the safe dose of bevacizumab. After approximately 20 cases are enrolled in the bevacizumab safety dose group identified in Cohort A, enrollment will be initiated in Cohort B. Cohort B will be QL1604 200 mg fixed dose q3w + bevacizumab safety dose, and random enrollment will be used for both Cohort A and Cohort B. The decision to initiate a cohort C study will be based on the preliminary results of the efficacy analysis of cohort A and cohort B. If a Cohort C study is initiated, the Cohort C dosing regimen will be QL1706 7.5 mg/kg q3w + bevacizumab safe dose q3w.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Liver Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
QL1706(5mg/kg)
Arm Type
Experimental
Arm Description
QL1706(5mg/kg) Combined with Bevacizumab
Arm Title
QL1604
Arm Type
Experimental
Arm Description
QL1604 Combined with Bevacizumab
Arm Title
QL1706(7.5mg/kg)
Arm Type
Experimental
Arm Description
QL1706(7.5mg/kg) Combined with Bevacizumab
Intervention Type
Drug
Intervention Name(s)
QL1706
Intervention Description
5 mg/kg#D1#Q3W IV or 7.5 mg/kg#D1#Q3W IV
Intervention Type
Drug
Intervention Name(s)
QL1604
Intervention Description
200mg#D1#Q3W IV
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Intervention Description
15 mg/kg#D1#Q3W IV or 7.5 mg/kg#D1#Q3W IV
Primary Outcome Measure Information:
Title
Objective remission rate (ORR)
Description
The ORR assessed according to RECIST v1.1
Time Frame
up to 1year
Secondary Outcome Measure Information:
Title
Duration of remission (DOR) Duration of remission (DOR) Duration of remission (DOR) Duration of remission (DOR)
Description
The DOR assessed according to RECIST v1.1
Time Frame
Every 6 weeks up to 48 weeks during study, and every 12 weeks after the end of treatment up to 1year.
Other Pre-specified Outcome Measures:
Title
Disease Control Rate (DCR) Disease Control Rate (DCR) Disease Control Rate (DCR)
Description
The DCR assessed according to RECIST v1.1
Time Frame
Every 6 weeks up to 48 weeks during study, and every 12 weeks after the end of treatment up to 1year.
Title
Progression free survival (PFS)
Description
The PFS and progression-free survival at 6 and 12 months (PFS6/12)
Time Frame
Every 6 weeks up to 48 weeks during study, and every 12 weeks after the end of treatment up to 1year.
Title
Overall survival (OS)
Description
The Overall survival and 1-year OS rate Overall survival Overall survival
Time Frame
From date of randomization until the date of death from any cause, , 12 months after the last use of the trial drug, or study completion/closure, whichever came first.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects participated voluntarily and signed an informed consent form. Age ≥ 18 years old at the time of signing the informed consent form, male or female. Advanced hepatocellular carcinoma diagnosed by histopathology or clinical diagnosis, with disease unsuitable for radical surgery and/or local treatment, or disease progression after surgery and/or local treatment. No prior systemic treatment for HCC. Child-Pugh liver function classification of grade A versus better grade B. Eastern Cooperative Oncology Group (ECOG) physical status score of 0-1. Expected survival ≥ 3 months. (9) Functional level of vital organs must be compliant prior to first administration of trial drug. (10) Subject agrees to use effective contraception for contraception from the time of signing the informed consent until 180 days after the last use of the trial drug. Females of childbearing age cannot be in pregnancy or breastfeeding. Exclusion Criteria: Subjects with symptomatic CNS metastases were not allowed to be enrolled. Patients with a history of other malignancies within 5 years prior to signing informed consent. Active autoimmune disease that may have worsened during the course of receiving study drug therapy. Concomitant disease that interferes with the subject's ability to complete the study. History of allogeneic hematopoietic stem cell transplantation or organ transplantation. HIV-positive patients; HCV antibody-positive and HCV RNA-positive patients; patients with co-infection with HBV and HCV. Patients with a known history of psychotropic substance abuse, alcoholism, or drug use Those who have participated in other clinical studies and have used other clinical trial drugs within 4 weeks prior to the use of the trial drug Prior immunotherapy or prior targeted therapy. PCP treatment requires 2 weeks of elution before enrollment and is prohibited during the trial. Known previous hypersensitivity to macromolecular protein agents, or any component of the test drug. Live vaccination within 4 weeks prior to the first administration of the test drug. History of hemoptysis, or history of gastrointestinal bleeding, intestinal obstruction and/or previous clinical signs or symptoms of gastrointestinal obstruction. Abdominal or bronchoesophageal fistula, gastrointestinal perforation or intra-abdominal abscess, major vascular disease. Current or recent treatment with aspirin, clopidogrel, or current or recent treatment with dipyridamole, ticlopidine, and cilostazol; use of anticoagulation therapy for therapeutic purposes
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Feng Professor Bi
Phone
028-85423203
Email
bifenggcp@163.com
Facility Information:
Facility Name
West China Hospital, Sichuan University
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Feng Bi, Professor
Phone
028-85423203
Email
bifenggcp@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Phase Ib/II Trial to Evaluate the Safety and Efficacy of QL1706 in Patients With Advanced Hepatocellular Carcinoma

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