Advanced Ovarian Carcinoma, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Pancreatic Cancer
Conditions
Keywords
Claudin 18.2 CAR-T
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
Detailed description
Following consent, patients must have tumor tissue evaluated by CLDN18.2 IHC assay. Patients meeting all eligibility criteria will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of investigational drug product (IMC002). Following manufacture of the drug product, subjects will receive preconditioning prior to IMC002 infusion. All subjects will be asked to continue to undergo long-term gene safety follow-up.
Interventions
BIOLOGICALClaudin 18.2 CAR-T
treatment with anti-claudin18.2 chimeric antigen receptor T-cell infusion
Sponsors
Changhai Hospital
Suzhou Immunofoco Biotechnology Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Accelerated titration and Bayesian optimal interval design (BION) dose escalation design
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients are eligible for screening for potential inclusion in the study: 1. The age is between 18 and 70 years old (including the boundary value), both male and female. 2. 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). 3. 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. 4. Estimated life expectancy≥12 weeks. 5. At least 1 measurable lesion per RECIST version1.1; 6. ECOG performance status score of 0-1. 7. The subject has adequate organ and bone marrow function. 8. All toxic reactions caused by previous anti-tumor therapy were relieved to grade 0-1 (according to NCI CTCAE version 5.0) or to an acceptable level for inclusion/
Exclusion criteria
. 9. 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). 10. Subjects must sign and date written informed consent. 11. Subjects must be voluntary and able to comply with predetermined treatment regimens, laboratory tests, follow-up and other research requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment Related adverse events (AEs) | day1 - month12 | Incidence of Treatment Related AEs, AEs of special interest and serious adverse events (SAEs) |
| Identification of Maximum Tolerated Dose (MTD) | day1 - day28 | Incidence of dose-limiting toxicities (DLTs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR)，as assessed by Investigators | day1 - month12 | The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1. |
| Duration of response (DOR)，as assessed by Investigators | day1 - month12 | Duration of response (DOR) is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death. |
| Disease control rate (DCR), as assessed by Investigators | day1 - month12 | Disease control rate (DCR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR) or Stable disease (SD) based on RECIST version 1.1. |
| Progression-free survival (PFS), as assessed by Investigators | day1 - month12 | Progression-free survival (PFS) was defined as the time from the date of first infusion of CT041 to the earliest date of the first objective documentation of progressive disease (PD) or death due to any cause. |
Countries
China
Contacts
Primary ContactZhengmao Lu, MD
Backup ContactAi Guoqiang, MD
Outcome results
None listed