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.
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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Enroll 3 subjects in the 2×10⁸ (Dose-1) cohort, followed by enrollment in the 4.0×10⁸ (Dose-2) cohort. If 1 subject experiences a dose limited toxicity (DLT) during observation period (4 weeks), enroll an additional 3 subjects. If ≥2 subjects experience a DLT after cell reinfusion in the initial 3 subjects of the Dose-1 cohort, the trial will be paused, and the investigator and the Data Monitoring Committee (DMC) will discuss dose reduction or protocol adjustment.For the Dose-2 cohort, initially enroll 3 subjects. If 1 subject experiences a DLT, enroll an additional 3 subjects. If DLTs ≤1, escalate to 1.0×10⁹ (Dose-3). For Dose-n (n=1,2,3), if the DLT proportion is ≥2/6 subjects, then Dose-n-1 will be designated as the RPD2. If no more than 2 DLT events occur in the Dose-3 cohort, then Dose-3 will be designated as the RPD2. For the first three subjects in each dose cohort, cell reinfusion for the next subject can only proceed after the previous subject has completed
Peking Union Medical College Hospital
Beijing, Beijing Municipality, China
Dose-Limiting Toxicity (DLT)
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
Time frame: from the start point of cell infusion to 28 days after cell infusion for each patient
Objective response rate(ORR)
Stable disease (SD)+ Partial remission (PR)+Complete remission (CR) in accordance with RECIST v1.1 criteria
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
Progression free survial(PFS)
Progression-Free Survival (PFS), Disease Control Rate (DCR), Duration of Response (DoR), Time to Response (TTR), Time to Tumor Progression (TTP), and Overall Survival (OS) as assessed by the investigator based on RECIST v1.1.
Time frame: 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
CAR copy detection in peripheral blood
Time frame: 6 hours, 12 hours, 24 hours, 72 hours, 7 days, 14 days, 28 days, 60 days, 90 days, after cell infusion
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