Chimeric Antigen Receptor Macrophages Targeting c-MET for Advanced Stage of Pancreatic Cancer Patients

NCT07553793 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: K6501
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer; Advanced Stage Cancer

Keywords

pancreatic cancer; chimeric antigen receptor; macrophages; C-MET

Outcome Measures

Primary Outcomes (2)

• 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

  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

  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

Secondary Outcomes (2)

• 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

Other Outcomes (1)

• Correlation between C-MET expression and anti-tumor efficacy

  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

Study Arms (1)

CAR-M-C-MET TREATMENT

EXPERIMENTAL

CAR-M-C-MET INTRAPERITONEAL INFUSION FOR TREATMENT

Biological: CAR-M-C-MET cell intraperitoneal infusion

Interventions

CAR-M-C-MET cell intraperitoneal infusion BIOLOGICAL

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

CAR-M-C-MET TREATMENT

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 0-1.
• 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:
• Note: Subjects must not receive transfusions or growth factor support within 7 days prior to the first dose for hematology assessments.
• Hematology:
• Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L.
• Platelet Count (PLT) ≥ 100 × 10⁹/L.
• Hemoglobin (HGB) ≥ 90 g/L or ≥ 5.6 mmol/L.

You may not qualify if:

• 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.
• Patients with a history of gastrointestinal bleeding within the past 6 months requiring blood transfusion, emergency room observation, or hospitalization.
• Patients with active peptic ulcers.
• Patients with a history of severe intra-abdominal infection.
• History of abdominal surgery within the past 3 months.
• Any uncontrolled active infection.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Related Publications (3)

• Zheng H, Yang X, Huang N, Yuan S, Li J, Liu X, Jiang Q, Wu S, Ju Y, Kleeff J, Yin X, Liao Q, Liu Q, Zhao Y. Chimeric antigen receptor macrophages targeting c-MET(CAR-M-c-MET) inhibit pancreatic cancer progression and improve cytotoxic chemotherapeutic efficacy. Mol Cancer. 2024 Dec 6;23(1):270. doi: 10.1186/s12943-024-02184-8.

  PMID: 39643883 RESULT

• Liu Q, Li J, Zheng H, Yang S, Hua Y, Huang N, Kleeff J, Liao Q, Wu W. Adoptive cellular immunotherapy for solid neoplasms beyond CAR-T. Mol Cancer. 2023 Feb 7;22(1):28. doi: 10.1186/s12943-023-01735-9.

  PMID: 36750830 RESULT

• Reiss KA, Angelos MG, Dees EC, Yuan Y, Ueno NT, Pohlmann PR, Johnson ML, Chao J, Shestova O, Serody JS, Schmierer M, Kremp M, Ball M, Qureshi R, Schott BH, Sonawane P, DeLong SC, Christiano M, Swaby RF, Abramson S, Locke K, Barton D, Kennedy E, Gill S, Cushing D, Klichinsky M, Condamine T, Abdou Y. CAR-macrophage therapy for HER2-overexpressing advanced solid tumors: a phase 1 trial. Nat Med. 2025 Apr;31(4):1171-1182. doi: 10.1038/s41591-025-03495-z. Epub 2025 Feb 7.

  PMID: 39920391 RESULT

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Quan Liao, MD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

• Wenming Wu, MD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qiaofei Liu, MD

CONTACT

861069152600; qfliu@aliyun.com

Study Design

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

Study Record Dates

• First Submitted: March 18, 2026
• First Posted: April 28, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: From the date when the results of the study are published to 3 years after the publication
• Access Criteria: when requsted reasonably

Locations

CN (1)