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A Clinical Study of TQB2618 Injection Monotherapy and Combination Regimen (With Penpulimab Injection ±Anlotinib Hydrochloride Capsules) in the Four or Later Lines of Treatment of Advanced Colorectal Cancer.

Primary Purpose

Colorectal Cancer

Status
Not yet recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
TQB2618 injection
Penpulimab injection
Anlotinib hydrochloride capsules
Sponsored by
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age: 18-75 years old; Eastern Cooperative Oncology Group Performance Status (ECOG PS) score: 0-1; Expected survival of more than 3 months; Histologically/cytologically confirmed metastatic colorectal cancer; The subjects should provide tumor tissues that meet the requirements for mismatch repair protein detection and Programmed cell death-Ligand 1 (PD-L1) expression level detection; Advanced colorectal cancer that progresses or is intolerant after receiving ≥3 lines of standard therapy; Failure of treatment with at least one of these drugs (TAS-102, Regorafenib, Fruquintinib); Confirmed presence of at least one measurable lesion according to Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1) criteria; Body weight ≥40 kg and Body Mass Index (BMI) ≥18.5 kg/m^2. The function of the main organs is good, and the laboratory examination meets the requirements; Female subjects of reproductive age should agree to use contraception during the study period and for 6 months after the end of the study; Male subjects should agree that contraception must be used during the study period and for 6 months after the end of the study period. Exclusion Criteria: Have had or are currently suffering from other malignant tumors within 3 years; Have any poorly controlled cardiovascular clinical symptoms or diseases; Patients with ulcerative colitis and Crohn's disease; Patients with active inflammatory bowel disease within the first 4 weeks of enrollment; Symptoms of hematemesis and hematochezia occurred within 6 months before screening, and the daily bleeding volume ≥ 2.5 mL; The presence of unmitigated toxic reactions of grade 1 or above as assessed per Common Terminology Criteria for Adverse Events (CTC-AE) due to any treatment prior to first administration, excluding hair loss; Patients who had received Programmed Death 1 (PD-1) or PD-L1 monoclonal antibody treatment and experienced ≥ grade 3 immune-related adverse reactions or stopped immune checkpoint inhibitor treatment due to immune-related adverse reactions; Active or uncontrolled severe infection (≥CTC AE grade 2 infection); Decompensated cirrhosis, active hepatitis; Poor diabetes control (fasting blood glucose > 10 mmol/L); Patients with renal failure requiring hemodialysis or peritoneal dialysis; Have a clear history of neurological or psychiatric disorders, including epilepsy or dementia, and require treatment; Had undergone a major surgical, open biopsy or significant traumatic injury within 4 weeks prior to the first dose of the study or expected to require major surgery during the study treatment. Patients with arterial/venous thrombosis events, such as cerebrovascular accident, deep vein thrombosis and pulmonary embolism, occurred within 6 months before the study treatment; Ascites with clinical significance, including any ascites that can be found by physical examination, ascites that have been treated in the past or still need to be treated, and only those who show a small amount of ascites but no symptoms on imaging can be included; Patients with an equal or greater amount of fluid in both pleural cavities, or a large amount of fluid in one pleural cavity, or have caused respiratory dysfunction and need drainage; The presence of unhealed wounds, ulcers or fractures; Have active tuberculosis, or have a history of active tuberculosis infection within 1 year prior to enrollment, or have a history of active tuberculosis infection more than 1 year prior to enrollment, but are not receiving treatment; There is a history of idiopathic pulmonary fibrosis, institutional pneumonia, drug-induced pneumonia, radiation pneumonia requiring treatment or active pneumonia with clinical symptoms, and interstitial lung disease requiring steroid hormone therapy; Have a history of immunodeficiency, including Human Immunodeficiency Virus (HIV) positive or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation or hematopoietic stem cell transplantation; Imaging shows that the tumor has invaded large blood vessels or is not clearly demarcated with blood vessels; Known central nervous system metastatic and/or cancerous meningitis; Have multiple factors that affect oral medication (such as inability to swallow, chronic diarrhea, and intestinal obstruction); Allergic to the ingredients of the investigational pharmaceutical preparations or excipients, or allergic to similar drugs; An active autoimmune disease requiring systemic treatment (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) has occurred within 2 years prior to initial medication; Have been diagnosed with immune deficiency or are receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy (dose > 10 mg/day prednisone or other therapeutic hormone) and continue to use within 2 weeks before the first dose; History of live attenuated vaccine vaccination within 28 days before the first dose or planned live attenuated vaccine vaccination during the study period; Have received systematic anti-tumor therapy and other interventional anti-tumor drug clinical trials such as radical surgery, chemotherapy, radical radiotherapy or immunotherapy, biotherapy, etc. within 4 weeks before the start of the study treatment; Within 2 weeks prior to the first drug use, the treatment of Chinese patent drugs with anti-tumor indications specified in the National Medical Products Administration (NMPA) approved drug instructions.

Sites / Locations

  • Fuyang Cancer Hospital
  • Huai Nan First People's Hospital
  • Fujian Cancer Hospital
  • The First Affiliated Hospital of Xiamen University
  • Meizhou People's Hospital (Huangtang Hospital)
  • Guangxi Medical University Cancer Hospital
  • Hunan Cancer Hospital
  • Jilin Cancer Hospital
  • The First Hospital of China Medical University
  • The First Affiliated Hospital of Air Force Medical University
  • The First Affiliated Hospital of Xi'an Jiao Tong University
  • Affiliated Hospital of Jining Medical University
  • Shanxi Cancer Hospital
  • The people's hospital of Leshan
  • Mianyang central hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

TQB2618 injection+Penpulimab injection +Anlotinib hydrochloride capsules

TQB2618 injection+Penpulimab injection

TQB2618 injection

Arm Description

TQB2618 injection combined with Penpulimab injection and Anlotinib hydrochloride capsules, 3 weeks as a treatment cycle.

TQB2618 injection combined with Penpulimab injection, 3 weeks as a treatment cycle.

TQB2618 injection, 3 weeks as a treatment cycle.

Outcomes

Primary Outcome Measures

Objective response rate (ORR)
According to RECIST 1.1 or Modified RECIST 1.1 for immune based therapeutics, (iRECIST) criteria, the proportion of subjects whose confirmed tumor volume reduction reached the pre-specified value and maintained the minimum time-frame requirements, i.e., the proportion of subjects with complete response (CR) and partial response (PR).

Secondary Outcome Measures

Overall survival (OS)
The time from randomization to death from any cause.
Progress free survival (PFS)
The time from randomization to the first disease progression or death from any cause, whichever occurs first.
Disease control rate (DCR)
Percentage of subjects with complete response, partial response, or stable disease as determined by RECIST 1.1 or iRECIST.
Duration of response (DOR)
From the time the tumor first assessed as complete or partial response to the time of first disease progression or death from any causes.
The incidence of adverse event (AE)
The incidence and severity of adverse events as determined by the Common Terminology Criteria for Adverse Events (CTC AE).
Anti-drug antibodies (ADA)
The occurrence of ADA
Neutralizing antibodies (NaB)
The occurrence of neutralizing antibodies

Full Information

First Posted
August 21, 2023
Last Updated
August 23, 2023
Sponsor
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT06010901
Brief Title
A Clinical Study of TQB2618 Injection Monotherapy and Combination Regimen (With Penpulimab Injection ±Anlotinib Hydrochloride Capsules) in the Four or Later Lines of Treatment of Advanced Colorectal Cancer.
Official Title
A Phase Ib Clinical Study to Evaluate the Efficacy and Safety of of TQB2618 Injection Monotherapy and Combination Regimen (With Penpulimab Injection ±Anlotinib Hydrochloride Capsules) in the Four or Later Lines of Treatment of Advanced Colorectal Cancer.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 2023 (Anticipated)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
July 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chia Tai Tianqing Pharmaceutical Group 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 clinical study to evaluate the efficacy and safety of TQB2618 injection as monotherapy and a combination regimen (with Penpulimab injection ± Anlotinib hydrochloride capsules) in the treatment of advanced colorectal cancer. 75 participants will be enrolled in the study. Objective response rate (ORR) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 is the primary endpoint.

6. Conditions and Keywords

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

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
TQB2618 injection+Penpulimab injection +Anlotinib hydrochloride capsules
Arm Type
Experimental
Arm Description
TQB2618 injection combined with Penpulimab injection and Anlotinib hydrochloride capsules, 3 weeks as a treatment cycle.
Arm Title
TQB2618 injection+Penpulimab injection
Arm Type
Experimental
Arm Description
TQB2618 injection combined with Penpulimab injection, 3 weeks as a treatment cycle.
Arm Title
TQB2618 injection
Arm Type
Experimental
Arm Description
TQB2618 injection, 3 weeks as a treatment cycle.
Intervention Type
Drug
Intervention Name(s)
TQB2618 injection
Intervention Description
TQB2618 is a monoclonal antibody targeting T cell immunoglobulin and mucin domain-3 (TIM-3) receptor.
Intervention Type
Drug
Intervention Name(s)
Penpulimab injection
Intervention Description
Penpulimab is a humanized Immunoglobulin G-1 (IgG1) monoclonal antibody that binds to human programmed cell death 1 (PD-1), a cell membrane protein that is primarily expressed on activated T cells and inhibits T cell activation.
Intervention Type
Drug
Intervention Name(s)
Anlotinib hydrochloride capsules
Intervention Description
Anlotinib hydrochloride is a muti-target tyrosine kinase inhibitor.
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
According to RECIST 1.1 or Modified RECIST 1.1 for immune based therapeutics, (iRECIST) criteria, the proportion of subjects whose confirmed tumor volume reduction reached the pre-specified value and maintained the minimum time-frame requirements, i.e., the proportion of subjects with complete response (CR) and partial response (PR).
Time Frame
From first administration until disease progression or withdrawal due to other reasons, estimated to not exceed 8 months.
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
The time from randomization to death from any cause.
Time Frame
Baseline up to death, estimated to not exceed 12 months
Title
Progress free survival (PFS)
Description
The time from randomization to the first disease progression or death from any cause, whichever occurs first.
Time Frame
From randomization to the time of disease progression or death from any cause, estimated to not exceed 12 months.
Title
Disease control rate (DCR)
Description
Percentage of subjects with complete response, partial response, or stable disease as determined by RECIST 1.1 or iRECIST.
Time Frame
From first administration to the time of disease progression or withdrawal from any cause, estimated to not exceed 12 months.
Title
Duration of response (DOR)
Description
From the time the tumor first assessed as complete or partial response to the time of first disease progression or death from any causes.
Time Frame
From first administration to the time of disease progression or death from any cause, estimated to not exceed 12 months.
Title
The incidence of adverse event (AE)
Description
The incidence and severity of adverse events as determined by the Common Terminology Criteria for Adverse Events (CTC AE).
Time Frame
From first administration to 28 days after withdrawal or the start time of the new anti-tumor treatment, whichever comes first.
Title
Anti-drug antibodies (ADA)
Description
The occurrence of ADA
Time Frame
Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 8 Day 1, 30 days and 90 days after the last dose. Each cycle is 21 days.
Title
Neutralizing antibodies (NaB)
Description
The occurrence of neutralizing antibodies
Time Frame
Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 8 Day 1, 30 days and 90 days after the last dose. Each cycle is 21 days.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age: 18-75 years old; Eastern Cooperative Oncology Group Performance Status (ECOG PS) score: 0-1; Expected survival of more than 3 months; Histologically/cytologically confirmed metastatic colorectal cancer; The subjects should provide tumor tissues that meet the requirements for mismatch repair protein detection and Programmed cell death-Ligand 1 (PD-L1) expression level detection; Advanced colorectal cancer that progresses or is intolerant after receiving ≥3 lines of standard therapy; Failure of treatment with at least one of these drugs (TAS-102, Regorafenib, Fruquintinib); Confirmed presence of at least one measurable lesion according to Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1) criteria; Body weight ≥40 kg and Body Mass Index (BMI) ≥18.5 kg/m^2. The function of the main organs is good, and the laboratory examination meets the requirements; Female subjects of reproductive age should agree to use contraception during the study period and for 6 months after the end of the study; Male subjects should agree that contraception must be used during the study period and for 6 months after the end of the study period. Exclusion Criteria: Have had or are currently suffering from other malignant tumors within 3 years; Have any poorly controlled cardiovascular clinical symptoms or diseases; Patients with ulcerative colitis and Crohn's disease; Patients with active inflammatory bowel disease within the first 4 weeks of enrollment; Symptoms of hematemesis and hematochezia occurred within 6 months before screening, and the daily bleeding volume ≥ 2.5 mL; The presence of unmitigated toxic reactions of grade 1 or above as assessed per Common Terminology Criteria for Adverse Events (CTC-AE) due to any treatment prior to first administration, excluding hair loss; Patients who had received Programmed Death 1 (PD-1) or PD-L1 monoclonal antibody treatment and experienced ≥ grade 3 immune-related adverse reactions or stopped immune checkpoint inhibitor treatment due to immune-related adverse reactions; Active or uncontrolled severe infection (≥CTC AE grade 2 infection); Decompensated cirrhosis, active hepatitis; Poor diabetes control (fasting blood glucose > 10 mmol/L); Patients with renal failure requiring hemodialysis or peritoneal dialysis; Have a clear history of neurological or psychiatric disorders, including epilepsy or dementia, and require treatment; Had undergone a major surgical, open biopsy or significant traumatic injury within 4 weeks prior to the first dose of the study or expected to require major surgery during the study treatment. Patients with arterial/venous thrombosis events, such as cerebrovascular accident, deep vein thrombosis and pulmonary embolism, occurred within 6 months before the study treatment; Ascites with clinical significance, including any ascites that can be found by physical examination, ascites that have been treated in the past or still need to be treated, and only those who show a small amount of ascites but no symptoms on imaging can be included; Patients with an equal or greater amount of fluid in both pleural cavities, or a large amount of fluid in one pleural cavity, or have caused respiratory dysfunction and need drainage; The presence of unhealed wounds, ulcers or fractures; Have active tuberculosis, or have a history of active tuberculosis infection within 1 year prior to enrollment, or have a history of active tuberculosis infection more than 1 year prior to enrollment, but are not receiving treatment; There is a history of idiopathic pulmonary fibrosis, institutional pneumonia, drug-induced pneumonia, radiation pneumonia requiring treatment or active pneumonia with clinical symptoms, and interstitial lung disease requiring steroid hormone therapy; Have a history of immunodeficiency, including Human Immunodeficiency Virus (HIV) positive or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation or hematopoietic stem cell transplantation; Imaging shows that the tumor has invaded large blood vessels or is not clearly demarcated with blood vessels; Known central nervous system metastatic and/or cancerous meningitis; Have multiple factors that affect oral medication (such as inability to swallow, chronic diarrhea, and intestinal obstruction); Allergic to the ingredients of the investigational pharmaceutical preparations or excipients, or allergic to similar drugs; An active autoimmune disease requiring systemic treatment (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) has occurred within 2 years prior to initial medication; Have been diagnosed with immune deficiency or are receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy (dose > 10 mg/day prednisone or other therapeutic hormone) and continue to use within 2 weeks before the first dose; History of live attenuated vaccine vaccination within 28 days before the first dose or planned live attenuated vaccine vaccination during the study period; Have received systematic anti-tumor therapy and other interventional anti-tumor drug clinical trials such as radical surgery, chemotherapy, radical radiotherapy or immunotherapy, biotherapy, etc. within 4 weeks before the start of the study treatment; Within 2 weeks prior to the first drug use, the treatment of Chinese patent drugs with anti-tumor indications specified in the National Medical Products Administration (NMPA) approved drug instructions.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ruihua Xu, Doctor
Phone
+86 13922206676
Email
13247323687@163.com
Facility Information:
Facility Name
Fuyang Cancer Hospital
City
Fuyang
State/Province
Anhui
ZIP/Postal Code
236010
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hesheng Qian, Bachelor
Phone
+86 13956814015
Email
qianhesheng@soho.com
Facility Name
Huai Nan First People's Hospital
City
Huainan
State/Province
Anhui
ZIP/Postal Code
232007
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yanshun Zhang, Bachelor
Phone
+86 18155498761
Email
zhangyanshun2006@163.com
Facility Name
Fujian Cancer Hospital
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350001
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rongbo Lin, Bachelor
Phone
+86 13705919382
Email
rongbo_lin@163.com
Facility Name
The First Affiliated Hospital of Xiamen University
City
Xiamen
State/Province
Fujian
ZIP/Postal Code
361003
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jiayi Li, Master
Phone
+86 13799792820
Email
ljy778848@qq.com
Facility Name
Meizhou People's Hospital (Huangtang Hospital)
City
Meizhou
State/Province
Guangdong
ZIP/Postal Code
514031
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiwen Huang, Bachelor
Phone
+86 13751952289
Email
811253076@qq.com
Facility Name
Guangxi Medical University Cancer Hospital
City
Nanning
State/Province
Guangxi
ZIP/Postal Code
530021
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yongqiang Li, Master
Phone
+86 13457161928
Email
lyq702702@126.com
Facility Name
Hunan Cancer Hospital
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410000
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhenyang Liu, Doctor
Phone
+86 18673181133
Email
1323081926@qq.com
Facility Name
Jilin Cancer Hospital
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130021
Country
China
Facility Name
The First Hospital of China Medical University
City
Shenyang
State/Province
Liaoning
ZIP/Postal Code
110002
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiujuan Qu, Doctor
Phone
+86 13604031355
Email
qu_xiujuan@hotmail.com
Facility Name
The First Affiliated Hospital of Air Force Medical University
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710000
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hai chuan Su, Doctor
Phone
+86 18629190366
Email
cntdgcp@163.com
Facility Name
The First Affiliated Hospital of Xi'an Jiao Tong University
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710000
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aili Suo, Doctor
Phone
+86 18991232561
Email
ailisuo@mail.xjtu.edu.cn
Facility Name
Affiliated Hospital of Jining Medical University
City
Jining
State/Province
Shandong
ZIP/Postal Code
272007
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Junye Wang, Bachelor
Phone
+86 18678766866
Email
18678766866@163.com
Facility Name
Shanxi Cancer Hospital
City
Taiyuan
State/Province
Shanxi
ZIP/Postal Code
030013
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenhui Yang, Doctor
Phone
+86 15835133400
Email
yangwenhui-10012@163.com
Facility Name
The people's hospital of Leshan
City
Leshan
State/Province
Sichuan
ZIP/Postal Code
614003
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jing Tian, Master
Phone
+86 13981302204
Email
5635452@qq.com
Facility Name
Mianyang central hospital
City
Mianyang
State/Province
Sichuan
ZIP/Postal Code
621009
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaobo Du, Doctor
Phone
+86 13550822229
Email
Duxiaobo2005@126.com

12. IPD Sharing Statement

Learn more about this trial

A Clinical Study of TQB2618 Injection Monotherapy and Combination Regimen (With Penpulimab Injection ±Anlotinib Hydrochloride Capsules) in the Four or Later Lines of Treatment of Advanced Colorectal Cancer.

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