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

NCT ID: NCT05946226

Last Updated: 2023-09-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-07
• Study Completion Date: 2025-12-31

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.

Conditions

Advanced Digestive System Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IMC002 dose 1-3

IMC002 single infusion

Group Type: EXPERIMENTAL

IMC002 injection

Intervention Type: BIOLOGICAL

three different IMC002 Doses will be escalated in "3+3" design

Interventions

IMC002 injection

three different IMC002 Doses will be escalated in "3+3" design

Intervention Type: BIOLOGICAL

Other Intervention Names

Autologous Claudin 18.2 specific CAR-T cell injection

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.

Exclusion Criteria

• 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).

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Suzhou Immunofoco Biotechnology Co., Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jianming Xu, Pro.

Role: PRINCIPAL_INVESTIGATOR

Chinese PLA General Hospital

Locations

Chinese PLA General Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, China

Site Status: NOT_YET_RECRUITING

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

Site Status: NOT_YET_RECRUITING

Shandong Cancer Hospital

Jinan, Shandong, China

Site Status: NOT_YET_RECRUITING

Renji Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

Site Status: NOT_YET_RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Site Status: NOT_YET_RECRUITING

First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status: NOT_YET_RECRUITING

Countries

China

Central Contacts

Jianming Xu, Pro.

Role: CONTACT

jmxu2003@163.com

13910866712

Rongrui Liu, MD

Role: CONTACT

liurongrui@hotmail.com

13911726595

Facility Contacts

Rongrui Liu

Role: primary

Jianwei Yang

Role: primary

Jiayi Li

Role: primary

Zuoxing Niu

Role: primary

Yingbin Liu

Role: primary

Hongfeng Gou

Role: primary

Weijia Fang

Role: primary

Other Identifiers

IMC002-RT01

Identifier Type: -

Identifier Source: org_study_id