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A Phase I Trial to Evaluate the Safety of IMC002 in Advanced Digestive System Tumors

Primary Purpose

Advanced Digestive System Tumor

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
IMC002 injection
Sponsored by
Suzhou Immunofoco Biotechnology Co., Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Digestive System Tumor

Eligibility Criteria

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

Inclusion Criteria: Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures Age > 18 and ≤70 years Patients with histologically or cytologically confirmed locally advanced/metastatic digestive system tumors including but not limited to advanced gastric cancer at least failed two lines of SOC, esophagogastric junction adenocarcinoma, and advanced pancreatic cancer failed at least one line SOC; Must have CLDN18.2 positive tumor expression histologically as determined by IHC (defined as positive rate of tumor cells≥40% and staining intensity ≥2+ ) or a biopsy if archived tumor sample is not available; representative tumor samples (primary or metastatic, archived or newly collected) are expected to be obtained Expected survival time ≥12 weeks Measurable or evaluable disease per RECIST1.1 ECOG performance status score of 0-1 Adequate organ and bone marrow function. If any laboratory test results are abnormal with reference to the criteria below, a repeat test can be performed within 1 week. If the test results are still abnormal, the patient fails screening. Recovery to grade 0-1 from AEs related to prior anticancer therapy or to an acceptable level for inclusion/exclusion criteria except alopecia and vitiligo Female of childbearing age must undergo a serum pregnancy test with negative results at screening and infusion; Female of childbearing age or male patients whose sexual partners are females of childbearing age are willing to take medically approved high-efficiency contraceptive measures such as intrauterine devices or condoms from the time of signing the informed consent to 1 year after infusion (women of childbearing age include premenopausal women and women within 24 months of post menopause). Exclusion Criteria: Pregnant and lactating women Human immunodeficiency virus (HIV) antibody positive; acute or chronic active hepatitis B; acute or chronic active hepatitis C Hepatitis. Syphilis antibody positive; cytomegalovirus (CMV) infection; Epstein-Barr (EB) virus infection. Active or clinically poorly controlled serious infections Uncontrollable pleural effusion, pericardial effusion and ascites effusion existed before enrollment. Extensive or diffuse lung or liver metastases Oxygen saturation ≤95% without oxygen inhalation With other diseases that may limit their participation in this study, such as pulmonary embolism, chronic obstructive pulmonary disease, symptomatic or poorly controlled interstitial lung disease, or clinically significant abnormal lung function tests Known prior or current hepatic encephalopathy requiring treatment; patients with current or history of central nervous system (CNS) disease. Autoimmune diseases; CNS metastases or meningeal metastases with clinical symptoms, or other evidence that the patient's CNS or meningeal metastases have not been controlled, and are judged not suitable for the study by the investigator Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure > 100 mmHg after standardized antihypertensive drug treatment); not well controlled diabetes mellitus [fasting plasma glucose (FPG) ≥10.2mmol/L]. Presence of any of clinical cardiac symptoms or disorders Evidence of major coagulopathy or other significant bleeding risk Systemic steroids equivalent to >15mg/day prednisone within 2 weeks before leukapheresis, except inhaled or topic steroids Requiring systemic therapy with corticosteroids or other immunosuppressive drugs during the treatment period. Presence of any active autoimmune disease, or history of autoimmune disease expect recur. Previous or concomitant other malignancies Have received other gene therapies including but not limited to any CAR-T and TCR-T therapy Anti-tumor therapies other than for the pretreatment and bridging therapies < 5 half-lives or 28 days (whichever is shorter) prior to study treatment Any investigational drugs or study drugs from a previous clinical study within 30 days prior to signing the informed consent; traditional Chinese medicine with anti-tumor activities within 2 weeks prior to the study treatment History of serious allergic disease or known allergy to any component of the study treatments With severe mental disorders Any issue that would impair the ability of the patient to receive or tolerate the planned treatment, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

Sites / Locations

  • Chinese PLA General HospitalRecruiting
  • Fujian Cancer Hospital
  • The First Affiliated Hospital of Xiamen University
  • Shandong Cancer Hospital
  • Renji Hospital, Shanghai Jiaotong University School of Medicine
  • West China Hospital of Sichuan University
  • First Affiliated Hospital of Zhejiang University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IMC002 dose 1-3

Arm Description

IMC002 single infusion

Outcomes

Primary Outcome Measures

Incidence and severity of dose-limiting toxicity (DLTs) within 28 days after IMC002 infusion
safety profile

Secondary Outcome Measures

ORR after IMC002 infusion
efficacy endpoints
Incidences and severity of treatment-related adverse events (TRAEs)
AEs
cytokine levels in the blood
IL-6, TNF-α, IL-10, IL-2, IFN-γ and other cytokines in peripheral
CAR-positive cell counts in peripheral blood
Cmax

Full Information

First Posted
June 15, 2023
Last Updated
September 27, 2023
Sponsor
Suzhou Immunofoco Biotechnology Co., Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05946226
Brief Title
A Phase I Trial to Evaluate the Safety of IMC002 in Advanced Digestive System Tumors
Official Title
A Phase I, Open-label, Multi-center, Dose-escalation Study to Evaluate the Safety, Feasibility, and Preliminary Efficacy of IMC002 in Patients With Claudin18.2-positive Advanced Digestive System Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 7, 2023 (Actual)
Primary Completion Date
December 1, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Suzhou Immunofoco Biotechnology Co., Ltd

4. Oversight

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

5. Study Description

Brief Summary
This is an open-label, multi-center, dose-escalation clinical study to evaluate the safety, feasibility, and preliminary efficacy of IMC002 in patients with CLDN18.2 positive digestive system tumors including but not limited to advanced gastric cancer, esophagogastric junction adenocarcinoma, and advanced pancreatic cancer.
Detailed Description
This is an open-label, multi-center, dose-escalation clinical study to evaluate the safety, feasibility, and preliminary efficacy of IMC002 in patients with CLDN18.2 positive digestive system tumors including but not limited to advanced gastric cancer, esophagogastric junction adenocarcinoma, and advanced pancreatic cancer. Approximately 9-18 patients with CLDN18.2-positive advanced digestive system tumors will be sequentially enrolled into 3 dose escalation cohorts to evaluate the safety and feasibility of autologous IMC002 treatment. Following enrolment, patients will undergo leukapheresis and IMC002 product preparation. Patients may receive bridging therapies if the disease progresses rapidly as determined by the investigator. After treatment with cyclophosphamide, fludarabine and nab-paclitaxel lymphodepletion, patients will be assigned to one of three dose escalation cohorts 1.0×108, 2.5×108, or 5.0×108 CAR-T cells. All patients will be given a single dose of IMC002 infusion. All patients will be followed as inpatient for 14 days. When all patients of a cohort have been observed for 28 days and no DLT criteria have been met, patients will be enrolled in next higher dose cohort. All enrolled patients will follow the same study treatment schedule and procedural requirements. This study is divided into a screening period, a lymphodepleting (LD) chemotherapy period, a treatment period, a primary follow-up period up to 12 weeks and a long-term follow-up period for up to 15 years post infusion.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Digestive System Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
A classic 3+3 model will be used to dose escalation 3 doses will be used: 1×10^8, 2.5×10^8 and 5×10^8 CAR-T cells/ patients
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
IMC002 dose 1-3
Arm Type
Experimental
Arm Description
IMC002 single infusion
Intervention Type
Biological
Intervention Name(s)
IMC002 injection
Other Intervention Name(s)
Autologous Claudin 18.2 specific CAR-T cell injection
Intervention Description
three different IMC002 Doses will be escalated in "3+3" design
Primary Outcome Measure Information:
Title
Incidence and severity of dose-limiting toxicity (DLTs) within 28 days after IMC002 infusion
Description
safety profile
Time Frame
within 28 days
Secondary Outcome Measure Information:
Title
ORR after IMC002 infusion
Description
efficacy endpoints
Time Frame
upto 96 weeks
Title
Incidences and severity of treatment-related adverse events (TRAEs)
Description
AEs
Time Frame
upto 96 weeks
Title
cytokine levels in the blood
Description
IL-6, TNF-α, IL-10, IL-2, IFN-γ and other cytokines in peripheral
Time Frame
upto 96 weeks
Title
CAR-positive cell counts in peripheral blood
Description
Cmax
Time Frame
upto 96 weeks
Other Pre-specified Outcome Measures:
Title
Immunogenicity parameters in peripheral blood
Description
Number of Participants with presence of human anti-CAR antibodies (ADA)
Time Frame
upto 96 weeks
Title
long-term safety
Description
Number of Participants with presence of RCL in peripheral blood
Time Frame
upto 96 weeks

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: Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures Age > 18 and ≤70 years Patients with histologically or cytologically confirmed locally advanced/metastatic digestive system tumors including but not limited to advanced gastric cancer at least failed two lines of SOC, esophagogastric junction adenocarcinoma, and advanced pancreatic cancer failed at least one line SOC; Must have CLDN18.2 positive tumor expression histologically as determined by IHC (defined as positive rate of tumor cells≥40% and staining intensity ≥2+ ) or a biopsy if archived tumor sample is not available; representative tumor samples (primary or metastatic, archived or newly collected) are expected to be obtained Expected survival time ≥12 weeks Measurable or evaluable disease per RECIST1.1 ECOG performance status score of 0-1 Adequate organ and bone marrow function. If any laboratory test results are abnormal with reference to the criteria below, a repeat test can be performed within 1 week. If the test results are still abnormal, the patient fails screening. Recovery to grade 0-1 from AEs related to prior anticancer therapy or to an acceptable level for inclusion/exclusion criteria except alopecia and vitiligo Female of childbearing age must undergo a serum pregnancy test with negative results at screening and infusion; Female of childbearing age or male patients whose sexual partners are females of childbearing age are willing to take medically approved high-efficiency contraceptive measures such as intrauterine devices or condoms from the time of signing the informed consent to 1 year after infusion (women of childbearing age include premenopausal women and women within 24 months of post menopause). Exclusion Criteria: Pregnant and lactating women Human immunodeficiency virus (HIV) antibody positive; acute or chronic active hepatitis B; acute or chronic active hepatitis C Hepatitis. Syphilis antibody positive; cytomegalovirus (CMV) infection; Epstein-Barr (EB) virus infection. Active or clinically poorly controlled serious infections Uncontrollable pleural effusion, pericardial effusion and ascites effusion existed before enrollment. Extensive or diffuse lung or liver metastases Oxygen saturation ≤95% without oxygen inhalation With other diseases that may limit their participation in this study, such as pulmonary embolism, chronic obstructive pulmonary disease, symptomatic or poorly controlled interstitial lung disease, or clinically significant abnormal lung function tests Known prior or current hepatic encephalopathy requiring treatment; patients with current or history of central nervous system (CNS) disease. Autoimmune diseases; CNS metastases or meningeal metastases with clinical symptoms, or other evidence that the patient's CNS or meningeal metastases have not been controlled, and are judged not suitable for the study by the investigator Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure > 100 mmHg after standardized antihypertensive drug treatment); not well controlled diabetes mellitus [fasting plasma glucose (FPG) ≥10.2mmol/L]. Presence of any of clinical cardiac symptoms or disorders Evidence of major coagulopathy or other significant bleeding risk Systemic steroids equivalent to >15mg/day prednisone within 2 weeks before leukapheresis, except inhaled or topic steroids Requiring systemic therapy with corticosteroids or other immunosuppressive drugs during the treatment period. Presence of any active autoimmune disease, or history of autoimmune disease expect recur. Previous or concomitant other malignancies Have received other gene therapies including but not limited to any CAR-T and TCR-T therapy Anti-tumor therapies other than for the pretreatment and bridging therapies < 5 half-lives or 28 days (whichever is shorter) prior to study treatment Any investigational drugs or study drugs from a previous clinical study within 30 days prior to signing the informed consent; traditional Chinese medicine with anti-tumor activities within 2 weeks prior to the study treatment History of serious allergic disease or known allergy to any component of the study treatments With severe mental disorders Any issue that would impair the ability of the patient to receive or tolerate the planned treatment, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jianming Xu, Pro.
Phone
13910866712
Email
jmxu2003@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Rongrui Liu, MD
Phone
13911726595
Email
liurongrui@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jianming Xu, Pro.
Organizational Affiliation
Chinese PLA General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chinese PLA General Hospital
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rongrui Liu
Facility Name
Fujian Cancer Hospital
City
Fuzhou
State/Province
Fujian
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianwei Yang
Facility Name
The First Affiliated Hospital of Xiamen University
City
Xiamen
State/Province
Fujian
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jiayi Li
Facility Name
Shandong Cancer Hospital
City
Jinan
State/Province
Shandong
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zuoxing Niu
First Name & Middle Initial & Last Name & Degree
Yuping Sun
Facility Name
Renji Hospital, Shanghai Jiaotong University School of Medicine
City
Shanghai
State/Province
Shanghai
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yingbin Liu
Facility Name
West China Hospital of Sichuan University
City
Chengdu
State/Province
Sichuan
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hongfeng Gou
Facility Name
First Affiliated Hospital of Zhejiang University School of Medicine
City
Hangzhou
State/Province
Zhejiang
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weijia Fang

12. IPD Sharing Statement

Plan to Share IPD
No

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A Phase I Trial to Evaluate the Safety of IMC002 in Advanced Digestive System Tumors

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