Trial Title:
A Phase I Trial to Evaluate the Safety of IMC002 in Advanced Digestive System Tumors
NCT ID:
NCT05946226
Condition:
Advanced Digestive System Tumor
Conditions: Official terms:
Digestive System Neoplasms
Gastrointestinal Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention 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
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
IMC002 injection
Description:
three different IMC002 Doses will be escalated in "3+3" design
Arm group label:
IMC002 dose 1-3
Other name:
Autologous Claudin 18.2 specific CAR-T cell injection
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Chinese PLA General Hospital
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Contact:
Last name:
Rongrui Liu
Facility:
Name:
Fujian Cancer Hospital
Address:
City:
Fuzhou
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jianwei Yang
Facility:
Name:
The First Affiliated Hospital of Xiamen University
Address:
City:
Xiamen
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jiayi Li
Facility:
Name:
Shandong Cancer Hospital
Address:
City:
Jinan
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Zuoxing Niu
Investigator:
Last name:
Yuping Sun
Email:
Sub-Investigator
Facility:
Name:
Renji Hospital, Shanghai Jiaotong University School of Medicine
Address:
City:
Shanghai
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Yingbin Liu
Facility:
Name:
West China Hospital of Sichuan University
Address:
City:
Chengdu
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Hongfeng Gou
Facility:
Name:
First Affiliated Hospital of Zhejiang University School of Medicine
Address:
City:
Hangzhou
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Weijia Fang
Start date:
September 7, 2023
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Suzhou Immunofoco Biotechnology Co., Ltd
Agency class:
Industry
Source:
Suzhou Immunofoco Biotechnology Co., Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05946226
