IMC001 for Clinical Research on Advanced Digestive System Malignancies

NCT05028933 | Recruiting Phase 1 DMC

• 1 other identifier: IMC001-CT04
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

A Phase I Clinical Study of Autologous T cells modified with chimeric antigen receptor targeting EpCAM ( EPCAM CAR-T) in Patients with malignant tumors of the digestive system (including advanced gastric cancer, colorectal cancer, liver cancer and pancreatic cancer) .

Conditions

Advanced Hepatocellular Carcinoma; Advanced Colorectal Cancer; Advanced Gastric Cancer; Advanced Pancreatic Cancer

Keywords

EpCAM; CAR-T

Outcome Measures

Primary Outcomes (3)

• Dose limited toxicity （DLT）

  Safety

  28 days

• Maximum Tolerated Dose（MTD）

  Tolerability evaluation

  28 days

• Adverse Event(AE)

  Incidence rate

  28 days

Secondary Outcomes (8)

• Number of Cells

  52 weeks

• Treatment Emergent Adverse Events(TEAE)

  Through study completion, an average of 3 years

• Antitumor efficacy-objective response rate (ORR)

  Through study completion, an average of 3 years

• Antitumor efficacy-Progression-free survival (PFS)

  Through study completion, an average of 3 years

• Antitumor efficacy-Duration of response (DOR)

  Through study completion, an average of 3 years

Study Arms (1)

EPCAM CAR-T

EXPERIMENTAL

The first stage: single dose escalation The classic "3+3" dose escalation test. The starting dose refers to the results of the previous test of subsequent subjects. In this study, 3 increasing dose levels were set up, with 3 to 6 cases per dose. * The first dose group is 3×10\^5/kg, allowing 10% dose error. * The second dose group is 1×10\^6/kg, allowing 10% dose error. * The third dose group is 3×10\^6/kg, allowing 10% dose error. Each dose group must complete the DLT observation before entering the next dose group; when the first subject in the same dose group has no DLT observed for at least 14 days after cell infusion, the subsequent subjects can receive cell infusion. The second stage: combined radiofrequency/microwave ablation for the treatment of advanced digestive system malignant tumors with liver metastases

Drug: EPCAM CAR-T

Interventions

EPCAM CAR-T DRUG

Pretreatment with fludarabine and cyclophosphamide EpCAM CAR-T Cells infusion

EPCAM CAR-T

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 70 years old (including boundary value), both male and female.
• The first stage requires patients with malignant tumors of the digestive system (including advanced gastric cancer, advanced colorectal cancer, advanced pancreatic cancer, advanced liver cancer) who have failed previous standard treatments and have no other feasible effective treatment methods. The documents for the diagnosis of advanced digestive system malignancies include imaging reports (CT/MRI) or pathological examination results. The second stage requires patients with liver metastases of advanced digestive system malignancies (including gastric cancer liver metastasis, colorectal cancer liver metastasis, and pancreatic cancer liver metastasis) who have previously failed standard treatment and have no other feasible effective treatment methods. The investigator can judge it. Perform radiofrequency/microwave ablation therapy. Documents for diagnosing liver metastases from advanced digestive system malignancies include imaging reports (CT/MRI) or pathological examination results.
• The subject's expected survival period is ≥12 weeks.
• According to the RECIST V.1.1 standard, subjects participating in the first phase of dose escalation must have at least one target lesion that can be evaluated stably. Participants participating in the second phase of EpCAM CAR-T infusion therapy combined with local radiofrequency/microwave ablation therapy must have at least one non-target disease in the liver that is suitable for radiofrequency/microwave ablation therapy.
• The histological staining of EpCAM in the biopsy tumor tissue sample is positive.
• Subjects in the second stage require Child-Pugh classification of liver function as A or B (score ≤ 7 points).
• ECOG stamina score 0～1.
• The subject has sufficient organ and bone marrow function. Laboratory screening must meet the following standards (refer to NCI CTCAE 5.0). All laboratory test results should be within the following stable range and there is no continuous supportive treatment.
• Blood test: white blood cell WBC≥1.5×10\^9/L; platelet count PLT ≥60×10\^9/L; hemoglobin content Hb ≥8.0g/dL; lymphocyte LYM≥0.4×10\^9/L;
• Blood biochemistry: serum creatinine≤1.5×ULN, if serum creatinine\>1.5×ULN, creatinine clearance rate\>50mL/min (calculated according to Cockcroft-Gault formula); serum total bilirubin≤1.5×ULN, alanine Aminotransferase (ALT)≤2×ULN, aspartate aminotransferase (AST)≤2×ULN (ALT≤5×ULN in patients with liver metastasis or liver cancer, AST≤5×ULN).
• Amylase and lipase ≤ 1.5 × ULN;
• Routine urine examination: urine protein \<2+
• The left ventricular ejection fraction (LVEF)\>45% in cardiac color Doppler ultrasound examination within one month.
• Fertility status: female patients of childbearing age or male patients whose sexual partners are females of childbearing age are willing to take effective contraceptive measures from the signing of the informed consent form to 6 months after the last cell infusion (females of childbearing age include premenopausal women and premenopausal women). Women within 2 years after menopause).
• The subject must sign and date a written informed consent form.

You may not qualify if:

• Subjects who meet any of the following conditions cannot be selected for this study;
• Women during pregnancy and lactation.
• Known history of human immunodeficiency virus (HIV) infection; acute or chronic active hepatitis B (HBsAg positive); acute or chronic active hepatitis C (HCV antibody positive). Syphilis antibody is positive; Epstein-Barr virus DNA quantitative\> 500 copies; Cytomegalovirus (CMV) infection (IgM positive).
• Severe infections that are active or poorly clinically controlled.
• At present, there is a heart disease requiring treatment or a poorly controlled hypertension (defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure \>90 mmHg after treatment with standardized antihypertensive drugs).
• The presence of any of the following cardiac clinical symptoms or diseases:
• Unstable angina;
• Myocardial infarction occurred within 1 year;
• ECG at rest QTc\>450ms (male) or QTc\>470ms (female);
• The resting state ECG examination found abnormalities of important clinical significance (such as abnormal heart rate, conduction, morphological characteristics, etc.) or complete left bundle branch block or third-degree heart block or second-degree heart block or PR Interval\> 250ms;
• There are factors that increase the risk of QTc prolongation and abnormal heart rate, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or sudden death of unexplained family members under 40 years old, or prolonged periods Period concomitant medication.
• Abnormal blood coagulation function (INR\>1.5×ULN), bleeding tendency or receiving thrombolysis or conventional anticoagulation therapy (such as warfarin or heparin), patients need long-term antiplatelet therapy (aspirin, dose\> 300mg/day; Clopidogrel, dose\>75mg/day).
• Subjects who need to use corticosteroids or other immunosuppressive drugs for systemic therapy during the treatment period.
• Before treatment, blood oxygen saturation ≤95% (referring to pulse oxygen detection).
• Have received systemic steroids equivalent to \>15 mg/day of prednisone within 2 weeks before apheresis, except for inhaled steroids.

Sponsors & Collaborators

• Zhejiang University: lead

Study Sites (2)

Renji Hospital, School of Medicine, Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, China

RECRUITING

First affiliated hospital, School of Medicine, Zhejiang University

Hangzhou, China

RECRUITING

Study Officials

• Weijia Fang

  The First Affiliated Hospital, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bowen Peng

CONTACT

+86 18870300543; bowen.peng@immunofoco.com

Saixue Zhang

CONTACT

+86 19857143032/8657187237646

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Model Details: single dose escalation The classic "3+3" dose escalation test. The starting dose refers to the results of the previous test of subsequent subjects. In this study, 3 increasing dose levels were set up, with 3 to 6 cases per dose.

Study Record Dates

• First Submitted: August 19, 2021
• First Posted: August 31, 2021
• Study Start: September 30, 2021
• Primary Completion: December 30, 2024
• Study Completion: December 31, 2024
• Last Updated: February 12, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)