Advanced Digestive System Tumor
Conditions
Brief 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.
Interventions
BIOLOGICALIMC002 injection
three different IMC002 Doses will be escalated in 3+3 design
Sponsors
Suzhou Immunofoco Biotechnology Co., Ltd
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of dose-limiting toxicity (DLTs) within 28 days after IMC002 infusion | within 28 days | safety profile |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR after IMC002 infusion | upto 96 weeks | efficacy endpoints |
| Incidences and severity of treatment-related adverse events (TRAEs) | upto 96 weeks | AEs |
| cytokine levels in the blood | upto 96 weeks | IL-6, TNF-α, IL-10, IL-2, IFN-γ and other cytokines in peripheral |
| CAR-positive cell counts in peripheral blood | upto 96 weeks | Cmax |
Other
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity parameters in peripheral blood | upto 96 weeks | Number of Participants with presence of human anti-CAR antibodies (ADA) |
| long-term safety | upto 96 weeks | Number of Participants with presence of RCL in peripheral blood |
Countries
China
Contacts
Primary ContactJianming Xu, Pro.
Backup ContactRongrui Liu, MD
Outcome results
None listed