Clinical Study of CLDN18.2-targeting CAR T Cells in Advanced Solid Tumors With Positive CLDN18.2 Expression

NCT05472857 | Recruiting Phase 1 DMC

• 1 other identifier: IMC002-CT01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, multi-center, Phase 1 clinical trial to evaluate the safety and efficacy of autologous claudin18.2 chimeric antigen receptor T-cell therapy in advanced solid tumors with positive CLDN18.2 expression

Conditions

Gastric Cancer; Pancreatic Cancer; Advanced Ovarian Carcinoma; Gastroesophageal Junction Adenocarcinoma

Keywords

Claudin 18.2 CAR-T

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment Related adverse events (AEs)

  Incidence of Treatment Related AEs, AEs of special interest and serious adverse events (SAEs)

  day1 - month12

• Identification of Maximum Tolerated Dose (MTD)

  Incidence of dose-limiting toxicities (DLTs)

  day1 - day28

Secondary Outcomes (4)

• Objective Response Rate (ORR)，as assessed by Investigators

  day1 - month12

• Duration of response (DOR)，as assessed by Investigators

  day1 - month12

• Disease control rate (DCR), as assessed by Investigators

  day1 - month12

• Progression-free survival (PFS), as assessed by Investigators

  day1 - month12

Study Arms (1)

anti-claudin18.2 chimeric antigen receptor T-cell therapy

EXPERIMENTAL

anti-claudin18.2 chimeric antigen receptor T-cell therapy，infusion

Biological: Claudin 18.2 CAR-T

Interventions

Claudin 18.2 CAR-T BIOLOGICAL

treatment with anti-claudin18.2 chimeric antigen receptor T-cell infusion

Also known as: IMC002

anti-claudin18.2 chimeric antigen receptor T-cell therapy

Eligibility Criteria

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

You may qualify if:

• The age is between 18 and 70 years old (including the boundary value), both male and female.
• Subjects with advanced CLDN 18.2 positive malignant solid tumors confirmed by histology or cytology in the past (including advanced gastric cancer or esophagogastric junction adenocarcinoma, advanced pancreatic cancer, and metastatic ovarian cancer without standard treatment).
• All subjects are required to provide tumor tissue specimens that can be used for CLDN 18.2 analysis, which must be tumor histopathological specimens within 24 months before signing the informed consent, or fresh biopsy specimens collected within 6 months before cell reinfusion ; CLDN 18.2 histological staining of biopsy tumor tissue specimens is positive (defined as staining intensity ≥ 1+, positive rate ≥ 10%), the recommended antibody for detection is: Anti-Claudin18.2 antibody.
• Estimated life expectancy≥12 weeks.
• At least 1 measurable lesion per RECIST version1.1;
• ECOG performance status score of 0-1.
• The subject has adequate organ and bone marrow function.

You may not qualify if:

• Fertility status: Female patients 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 from the time of signing the informed consent to 6 months after the last cell infusion or condoms (women of childbearing age include premenopausal women and women within 24 months of postmenopause).
• Subjects must sign and date written informed consent.
• Subjects must be voluntary and able to comply with predetermined treatment regimens, laboratory tests, follow-up and other research requirements.
• Subjects who meet any of the following conditions are not eligible for this study;
• Pregnant and lactating women.
• Known history of human immunodeficiency virus (HIV) infection; acute or chronic active hepatitis B (HBsAg positive or HBsAb positive, and HBV-DNA positive); acute or chronic active hepatitis C (HCV antibody positive) , and HCV-RNA was positive). Syphilis antibody positive; EB virus DNA quantification \>500 copies (or according to the positive standard detected by each research center); cytomegalovirus (CMV) infection (IgM positive).
• Serious infection in active stage or poorly controlled clinically.
• There is currently a heart disease requiring treatment or hypertension that is poorly controlled by the investigator (defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure \> 90 mmHg after standardized antihypertensive drug treatment).
• Within 6 months before cell reinfusion, any of the following cardiac clinical symptoms or diseases: left ventricular ejection fraction (LVEF) \< 50%; previous history of coronary heart disease, myocardial infarction, severe heart failure and severe arrhythmia.
• Evidence of major coagulation disorder or other significant bleeding risk: including but not limited to receiving conventional anticoagulation therapy (such as warfarin or heparin). Patients require long-term antiplatelet therapy (aspirin, dose \>300mg/day; clopidogrel, dose \>75mg/day); dipyridamole, ticlopidine or cilostazol, etc.
• Subjects requiring systemic therapy with corticosteroids or other immunosuppressive drugs during the treatment period.
• Blood oxygen saturation ≤95% before treatment (refers to pulse oxygen detection).
• Diffuse lung metastases.
• Past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis, and symptomatic interstitial lung disease or active pneumonia found on chest CT scan within 4 weeks before the first study drug treatment.
• Uncontrollable pleural effusion, pericardial effusion and ascites effusion existed before enrollment.

Sponsors & Collaborators

• Suzhou Immunofoco Biotechnology Co., Ltd: lead
• Changhai Hospital: collaborator

Study Sites (1)

Changhai Hospital

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Luo Tianhang, MD

  Changhai Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhengmao Lu, MD

CONTACT

+86 21 50907211; luzhengmao82@126.com

Ai Guoqiang, MD

CONTACT

86-18482022722; guoqiang.ai@immunofoco.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Accelerated titration and Bayesian optimal interval design (BION) dose escalation design

Study Record Dates

• First Submitted: July 20, 2022
• First Posted: July 25, 2022
• Study Start: August 8, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: March 6, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)