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Advanced Hepatocellular CarcinomaPhase 1NCT05028933

IMC001 for Clinical Research on Advanced Digestive System Malignancies

A Phase 1 study testing EPCAM CAR-T in people with Advanced Hepatocellular Carcinoma and Advanced Colorectal Cancer, run by Zhejiang University at 2 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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) . Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
EPCAM CAR-T
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
2 sitesChina
Study dates
30 Sep 2021to 31 Dec 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.
  • The subject must be willing and able to comply with the predetermined treatment plan, laboratory examination, follow-up and other research requirements.

Who cannot join

  • 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:
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  • 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.
  • Before the pretreatment of chemotherapy for removing lymphocytes, the subject developed a new arrhythmia, including but not limited to arrhythmia that cannot be controlled with drugs, hypotension that requires vasopressor, bacteria, fungi, or intravenous antibiotics that require intravenous antibiotics. Viral infection. Subjects who use test antibiotics to prevent infection are up to the investigator to determine whether participants can continue to participate in the test.
  • Known past or current hepatic encephalopathy requiring treatment; patients with current or history of central nervous system disease, such as epileptic seizures, cerebral ischemia/hemorrhage, dementia, cerebellar disease or any associated central nervous system involvement Autoimmune disease; central nervous system metastasis or meningeal metastasis with clinical symptoms, or other evidence that the patient's central nervous system metastasis or meningeal metastasis has not been controlled, and the investigator judged that it is not suitable for inclusion in the group.
  • The results of the imaging examination of the subjects in the second stage: the liver is replaced by tumors ≥50%, or the main portal vein tumor thrombus, or the tumor thrombus invades the mesenteric vein/inferior vena cava; or there are central or extensive non-metastatic lesions .
  • Patients who have had other malignant tumors before or at the same time, with the following exceptions:
  • Adequately treated basal cell or squamous cell carcinoma (enough wound healing is required before being enrolled in the study);
  • Cervical cancer or breast cancer in situ, after curative treatment, there is no sign of recurrence at least 3 years before the study;
  • The primary malignant tumor has been completely removed and completely remitted for ≥5 years.
  • Have received other CAR-T treatments and TCR-T treatments in the past.
  • Received anti-PD-1/PD-L1 monoclonal antibody treatment within 4 weeks before apheresis.
  • Subjects who have received other gene therapy in the past.
  • Subjects with severe mental disorders.
  • Participated in other clinical studies in the past month.
  • The researcher assesses that the subject is unable or unwilling to comply with the requirements of the research protocol.
  • The subject withdrew from the study due to various reasons and could not participate in the study again.

Trial locations and contacts

2 sites in 1 country.

Bowen Peng contact

+86 18870300543

bowen.peng@immunofoco.com

Saixue Zhang contact

+86 19857143032/8657187237646

China2 sites, 2 recruiting

  • First affiliated hospital, School of Medicine, Zhejiang University

    Hangzhou

    Weijia Fang, Doctor

    Recruiting

  • Renji Hospital, School of Medicine, Shanghai Jiao Tong University

    Shanghai, Shanghai Municipality

    Yongle Xie, 86-13585921958/862168383131

    Yimin Mao, Dr

    Recruiting

Other trials in China

About this study

Official title: Autologous T Cells Modified by Chimeric Antigen Receptor Targeting EpCAM for Clinical Research on Advanced Digestive System Malignancies

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) .

Read the detailed description

This is a phase I open-label, single and multiple infusion, dose escalation/cohort expansion study to evaluate the safety, cell pharmacokinetics, and preliminary efficacy of EPCAM CAR-T, infused intravenously in subjects who have been diagnosed with advanced malignant tumors of the digestive system (including advanced gastric cancer, colorectal cancer, liver cancer and pancreatic cancer) and refractory or intolerant to current standard systemic treatment.

Primary objectives:

•To evaluate the safety and tolerability of EPCAM CAR-T infused intravenously at escalating doses in patients with advanced malignant tumors of the digestive system.

Secondary objectives:

  1. The treatment of EpCAM CAR-T for patients with advanced digestive system malignancies, according to the dose-limiting toxicity and clinical response, including Possible side effects, determine the maximum tolerated dose (MTD), extended recommended dose (RDE) and/or recommended phase II dose (RP2D).
  2. Assess the correlation between the pharmacodynamic (PD) biomarkers of IMC001 and clinical efficacy; EpCAM CAR-T expands and persists in vivo Correlation between sexual and pharmacodynamic (PD) biomarkers and adverse events.
  3. To evaluate the preliminary anti-tumor efficacy of EpCAM CAR-T in patients with advanced digestive system malignancies. According to the evaluation criteria for the efficacy of solid tumors (RECIST) Version V.1.1, Evaluation Criteria for Efficacy of Immunotherapy for Solid Tumors (iRECIST), using objective response rate(ORR), duration of remission (DOR), disease control rate (DCR) and progression-free survival (PFS) description preliminary Anti-tumor activity.
  4. The incidence of treatment-related adverse events.

Exploratory purpose:

  1. Assess changes in immune status of EPCAM CAR-T treatment.
  2. Assess the change of CTC in the peripheral blood of patients and the clearance effect of CAR-T cell treatment on CTC.
Being tested
EPCAM CAR-T
Keywords
EpCAM, CAR-T

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EPCAM CAR-TDrug

    Pretreatment with fludarabine and cyclophosphamide EpCAM CAR-T Cells infusion

Study groups in NCT05028933
Study groupRoleWhat they receive
EPCAM CAR-TExperimentalThe 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
Receives: Drug: EPCAM CAR-T

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limited toxicity （DLT）

    Safety

    Measured: 28 days

  2. Maximum Tolerated Dose（MTD）

    Tolerability evaluation

    Measured: 28 days

  3. Adverse Event(AE)

    Incidence rate

    Measured: 28 days

Secondary outcomes (8)

  1. Number of Cells

    Pharmacokinetics is the "Implantation endpoint" which is defined as the number of copies of the IMC001 DeoxyriboNucleic Acid（DNA）in peripheral blood detected at each visit after infusion until any two consecutive test results are negative or below the detection limit. Duration of IMC001 Cell persistence is the period from the day of infusion to the first negative test result or result lower than the detection limit

    Measured: 52 weeks

  2. Treatment Emergent Adverse Events(TEAE)

    Incidence rate

    Measured: Through study completion, an average of 3 years

  3. Antitumor efficacy-objective response rate (ORR)

    The period from the first evaluation of CR or PR to the first evaluation of PD or death of any cause.

    The period from the first evaluation of CR or PR to the first evaluation of PD or death of any cause.

    Measured: Through study completion, an average of 3 years

  4. Antitumor efficacy-Progression-free survival (PFS)

    The period from the day when the subject receives the first study treatment to the first recorded tumor progression(whether treated or not) or death of any cause, which occurs first

    Measured: Through study completion, an average of 3 years

  5. Antitumor efficacy-Duration of response (DOR)

    The period from the first evaluation of CR or PR to the first evaluation of PD or death of any cause.

    Measured: Through study completion, an average of 3 years

  6. Antitumor efficacy-Overall survival (OS)

    The period from the first study treatment to any cause of death

    Measured: Through study completion, an average of 3 years

  7. Antitumor efficacy-Disease control rate (DCR)

    The number of cases in which response (PR + CR) and stable disease (SD) are achieved from the start of cell infusion/the total number of evaluable cases (%).

    Measured: Through study completion, an average of 3 years

  8. Number of circulating tumor cells (CTC) in peripheral blood

    The number of CTC before and after treatment was evaluated

    Measured: Through study completion, an average of 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2021
  2. Study start30 Sep 2021
  3. Primary completion30 Dec 2024 (estimated)
  4. Study completion31 Dec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
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.
Masking
None (open label)
Enrolment
48 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05028933
Sponsor's protocol ID
IMC001-CT04
Status last verified
Feb 2024
First submitted
19 Aug 2021
Last updated
12 Feb 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing EPCAM CAR-T in people with Advanced Hepatocellular Carcinoma and Advanced Colorectal Cancer, run by Zhejiang University at 2 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 12 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Bowen Peng (+86 18870300543, bowen.peng@immunofoco.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limited toxicity （DLT） (time frame: 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05028933.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2024.

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