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.

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: TQB2618 injection; Drug: Penpulimab injection; Drug: Anlotinib hydrochloride capsules

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ruihua Xu, Doctor; Phone Number: +86 13922206676; Email: 13247323687@163.com

Study Locations

• China
  • Anhui
    • Fuyang, Anhui, China, 236010
      • Recruiting
      • Fuyang Cancer Hospital
      • Contact: Hesheng Qian, Bachelor; Phone Number: +86 13956814015; Email: qianhesheng@soho.com
    • Huainan, Anhui, China, 232007
      • Not yet recruiting
      • Huai Nan First People's Hospital
      • Contact: Yanshun Zhang, Bachelor; Phone Number: +86 18155498761; Email: zhangyanshun2006@163.com
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Recruiting
      • Fujian Cancer Hospital
      • Contact: Rongbo Lin, Bachelor; Phone Number: +86 13705919382; Email: rongbo_lin@163.com
    • Xiamen, Fujian, China, 361003
      • Not yet recruiting
      • The First Affiliated Hospital of Xiamen University
      • Contact: Jiayi Li, Master; Phone Number: +86 13799792820; Email: ljy778848@qq.com
  • Guangdong
    • Meizhou, Guangdong, China, 514031
      • Not yet recruiting
      • Meizhou People's Hospital (Huangtang Hospital)
      • Contact: Xiwen Huang, Bachelor; Phone Number: +86 13751952289; Email: 811253076@qq.com
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Recruiting
      • Guangxi Medical University Cancer Hospital
      • Contact: Yongqiang Li, Master; Phone Number: +86 13457161928; Email: lyq702702@126.com
  • Hunan
    • Changsha, Hunan, China, 410000
      • Not yet recruiting
      • Hunan Cancer Hospital
      • Contact: Zhenyang Liu, Doctor; Phone Number: +86 18673181133; Email: 1323081926@qq.com
  • Jilin
    • Changchun, Jilin, China, 130021
      • Recruiting
      • Jilin Cancer Hospital
      • Contact: Ying Cheng, Doctor; Phone Number: +86 0431-80596315; Email: jl.cheng@163.com
  • Liaoning
    • Shenyang, Liaoning, China, 110002
      • Not yet recruiting
      • The First Hospital of China Medical University
      • Contact: Xiujuan Qu, Doctor; Phone Number: +86 13604031355; Email: qu_xiujuan@hotmail.com
  • Shaanxi
    • Xi'an, Shaanxi, China, 710000
      • Not yet recruiting
      • The First Affiliated Hospital of Air Force Medical University
      • Contact: Hai chuan Su, Doctor; Phone Number: +86 18629190366; Email: cntdgcp@163.com
    • Xi'an, Shaanxi, China, 710000
      • Not yet recruiting
      • The First Affiliated Hospital of Xi'an Jiao Tong University
      • Contact: Aili Suo, Doctor; Phone Number: +86 18991232561; Email: ailisuo@mail.xjtu.edu.cn
  • Shandong
    • Jining, Shandong, China, 272007
      • Not yet recruiting
      • Affiliated Hospital of Jining Medical University
      • Contact: Junye Wang, Bachelor; Phone Number: +86 18678766866; Email: 18678766866@163.com
  • Shanxi
    • Taiyuan, Shanxi, China, 030013
      • Not yet recruiting
      • Shanxi Cancer Hospital
      • Contact: Wenhui Yang, Doctor; Phone Number: +86 15835133400; Email: yangwenhui-10012@163.com
  • Sichuan
    • Leshan, Sichuan, China, 614003
      • Not yet recruiting
      • The people's hospital of Leshan
      • Contact: Jing Tian, Master; Phone Number: +86 13981302204; Email: 5635452@qq.com
    • Mianyang, Sichuan, China, 621009
      • Not yet recruiting
      • Mianyang Central Hospital
      • Contact: Xiaobo Du, Doctor; Phone Number: +86 13550822229; Email: Duxiaobo2005@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TQB2618 injection+Penpulimab injection +Anlotinib hydrochloride capsules; TQB2618 injection combined with Penpulimab injection and Anlotinib hydrochloride capsules, 3 weeks as a treatment cycle.	Drug: TQB2618 injection; TQB2618 is a monoclonal antibody targeting T cell immunoglobulin and mucin domain-3 (TIM-3) receptor.; Drug: Penpulimab injection; 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.; Drug: Anlotinib hydrochloride capsules; Anlotinib hydrochloride is a muti-target tyrosine kinase inhibitor.
Experimental: TQB2618 injection+Penpulimab injection; TQB2618 injection combined with Penpulimab injection, 3 weeks as a treatment cycle.	Drug: TQB2618 injection; TQB2618 is a monoclonal antibody targeting T cell immunoglobulin and mucin domain-3 (TIM-3) receptor.; Drug: Penpulimab injection; 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.
Experimental: TQB2618 injection; TQB2618 injection, 3 weeks as a treatment cycle.	Drug: TQB2618 injection; TQB2618 is a monoclonal antibody targeting T cell immunoglobulin and mucin domain-3 (TIM-3) receptor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	From first administration until disease progression or withdrawal due to other reasons, estimated to not exceed 8 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	The time from randomization to death from any cause.	Baseline up to death, estimated to not exceed 12 months
Progress free survival (PFS)	The time from randomization to the first disease progression or death from any cause, whichever occurs first.	From randomization to the time of disease progression or death from any cause, estimated to not exceed 12 months.
Disease control rate (DCR)	Percentage of subjects with complete response, partial response, or stable disease as determined by RECIST 1.1 or iRECIST.	From first administration to the time of disease progression or withdrawal from any cause, estimated to not exceed 12 months.
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.	From first administration to the time of disease progression or death from any cause, estimated to not exceed 12 months.
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).	From first administration to 28 days after withdrawal or the start time of the new anti-tumor treatment, whichever comes first.
Anti-drug antibodies (ADA)	The occurrence of ADA	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.
Neutralizing antibodies (NaB)	The occurrence of neutralizing antibodies	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.

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: August 21, 2023
• First Submitted That Met QC Criteria: August 23, 2023
• First Posted (Actual): August 25, 2023

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: TQ2618-AK105-Ib-05

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No