Human Chimeric Antigen Receptor Macrophages Targeting C-MET for C-MET-positive Advanced Stage of Pancreatic Cancer Patients: A Single-arm, Single-center, IIT Study
Overview
- Phase
- Phase 1
- Status
- Not yet recruiting
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Dose-Limiting Toxicity (DLT)
Overview
Brief Summary
Chemotherapy is the first-line treatment for advanced-stage pancreatic cancer patients. However, drug resistance always occurs within 6 months. For these patients, no effective treatment is available. Chimeric antigen receptor macrophage targeting C-MET( CAR-M-C-MET) is a novel cellular therapy for these patients. In this clinical trial, advanced-stage pancreatic cancer patients when tumor progression after chemotherapy are enrolled to test the safety and anti-tumor efficacy of this novel cellular therapy.
Detailed Description
Chimeric antigen receptor macrophages (CAR-M) represent one of the most promising cellular immunotherapies for solid tumors. Patients with advanced-stage pancreatic cancer face an extremely dismal prognosis, particularly following the failure of chemotherapy. This trial investigates the role of CAR-M cellular therapy in advanced pancreatic cancer patients who have progressed after prior chemotherapy.
C-MET is a target highly expressed in the majority of pancreatic cancer tissues. In this study, a chimeric antigen receptor targeting c-MET is designed and cloned into an adenoviral vector. Peripheral blood mononuclear cells are collected from participants, and CD14-positive monocytes are isolated. These monocytes are then induced and expanded using Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF), and subsequently transduced with the c-MET-specific CAR-adenoviral vector to generate CAR-M-c-MET. The final cell product is cryopreserved and later administered via intraperitoneal infusion. Each patient receives a single dose of cell infusion.
Following infusion, the safety, efficacy, and pharmacokinetics of CAR-M-c-MET therapy are comprehensively evaluated.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Able to understand and voluntarily sign a written informed consent form.
- •Willing and able to comply with the scheduled visit and treatment plan, laboratory tests, and other study requirements.
- •Aged ≥ 18 years and ≤ 75 years on the day of signing the informed consent form, male or female.
- •ECOG performance status of 0-
- •Histologically or cytologically confirmed locally unresectable or abdominopelvic metastatic pancreatic ductal adenocarcinoma.
- •Pancreatic cancer patients who have failed at least one prior line of therapy or are intolerant to such therapy.
- •Medium to high expression of C-MET in pancreatic cancer tissue (defined as ++ or higher, with positive cells \> 25%).
- •At least one measurable lesion according to RECIST v1.1 criteria.
- •Expected survival ≥ 4 months.
- •Adequate organ function as defined by the following laboratory requirements:
Exclusion Criteria
- •Received the following anti-tumor treatments prior to apheresis: Immunomodulatory therapy within 7 days; Cytotoxic therapy within 14 days; Investigational medication, targeted therapy, or anti-tumor traditional Chinese medicine within 28 days.
- •Previously received CAR-T cell therapy or other cell therapies targeting any antigen.
- •Liver metastases occupying more than 30% of the total liver volume.
- •History of other concurrent malignancies, except for the following: Completely resected or eradicated basal cell carcinoma and squamous cell carcinoma of the skin, cervical carcinoma in situ, minute/microscopic papillary thyroid carcinoma, minute/microscopic breast cancer, and other malignancies with an extremely low risk of recurrence or metastasis.
- •Patients with a history of autoimmune disease requiring immunosuppressive medication or hormone therapy (excluding physiological replacement doses).
- •History of severe Central Nervous System (CNS) disease, such as grand mal seizures, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, or psychosis.
- •Patients with a left ventricular ejection fraction (LVEF) \< 50%, severe structural cardiac abnormalities, or arrhythmias requiring medical treatment.
- •Patients with a history of medical treatment for intestinal obstruction, or those with imaging findings during screening indicating intestinal obstruction requiring treatment.
- •Moderate to severe hepatic steatosis (fatty liver).
- •Patients with moderate to severe cirrhosis (Child-Pugh Class A or worse) and significant portal hypertension.
Arms & Interventions
CAR-M-C-MET TREATMENT
CAR-M-C-MET INTRAPERITONEAL INFUSION FOR TREATMENT
Intervention: CAR-M-C-MET cell intraperitoneal infusion (Biological)
Outcomes
Primary Outcomes
Dose-Limiting Toxicity (DLT)
Time Frame: from the start point of cell infusion to 28 days after cell infusion for each patient
Any clinically significant Grade 3 or higher toxicity involving a major organ system, as defined by NCI CTCAE version 5, occurring within 28 days post-infusion and persisting for more than 72 hours; II. Any Grade 4 Cytokine Release Syndrome (CRS) occurring during the treatment period that does not resolve to Grade 2 or lower within 72 hours, or any death attributed to CRS; III. Any Grade 3 CRS occurring during the treatment period that does not resolve to Grade 2 or lower within 7 days; IV. Any Grade 3 or higher autoimmune toxicity occurring during the
Objective response rate（ORR）
Time Frame: From date of signing the informed consent until the date of first documented progression from any cause, whichever came first, assessed up to 96 weeks
Stable disease (SD）+ Partial remission （PR）+Complete remission （CR） in accordance with RECIST v1.1 criteria
Secondary Outcomes
- Progression free survial（PFS）(From date of signing the informed consent until the date of first documented progression or death from any cause, whichever came first, assessed up to 96 weeks)
- Pharmacokinetics of CAR-M(6 hours, 12 hours, 24 hours, 72 hours, 7 days, 14 days, 28 days, 60 days, 90 days, after cell infusion)