CAR-NK Cells (CL-NK-001) in Pancreatic Cancer

A dose-escalation study will evaluate the safety, tolerability and efficacy of CAR-NK cells (CL-NK-001) in patients with locally advanced, metastatic, or recurrent pancreatic cancer.

Inclusion criteria

• Aged 18-70 years;
• Locally advanced, metastatic, or recurrent pancreatic cancer, with immunohistochemical detection of eGR1 (membrane positive tumor cell rate >40% and expression intensity ≥2+), who have failed, been intolerant to or reject standard treatment;
• At least 1 measurable lesion according to RECIST 1.1;
• Have not received anti-tumor treatment for at least 4 weeks;
• ECOG performance status of 0-2;
• Estimated life expectancy more than 12 weeks;
• Hematology: neutrophils ≥ 1.5×10^9/L, lymphocytes ≥ 0.8×10^9/L, hemoglobin ≥ 100 g/L, and platelets ≥ 75 × 10^9/L;
• Blood biochemistry: total bilirubin ≤ 2×ULN, alanine aminotransferase ≤ 3×ULN, aspartate aminotransferase ≤ 3×ULN, and creatinine clearance ≥ LLN (Cockcroft-Gault formula);
• Volunteer to participate in this clinical study and willing to sign written informed consent.

Exclusion criteria

• Evidence of central nervous system involvement;
• Have received adoptive cell therapy;
• Patients with any uncontrolled active infection, including but not limited to: HBV, HCV, HIV, or treponema pallidum serology positive;
• Vaccinated with a live attenuated vaccine within 3 months;
• History of immunodeficiency;
• Active autoimmune disease;
• Have severe conditions, including but not limited to: (1) severe respiratory diseases; (2) severe cardiovascular diseases (previous history of CABG/PCI; myocardial infarction/unstable angina pectoris, congestive heart failure of NYHA III-IV, left ventricular ejection fraction < 50%, or poorly controlled hypertension within 6 months; QTc interval > 480ms, long or short QT syndrome; previous history of ventrical arrhythmia, or ventrical arrhythmia under anti-arrhythmic drugs/ICD); (3) poorly controlled diabetes and other metabolic diseases; (4) severe gastrointestinal diseases (severe gastrointestinal bleeding, severe diarrhea of CTCAE ≥ 2, or severe gastrointestinal obstruction needing intervention);
• Possible severe adverse events, allergy or other contraindications to drugs or its component under study;
• Pregnant or lactating women;
• History of neurological or psychological disorders;
• Not suitable to participate this clinical study judged by the investigator.