CAR-NK cell therapy (CL-NK-003) for pancreatic cancer

A Clinical Study of CAR-NK Cells (CL-NK-003) in Patients With Advanced Pancreatic Cancer

This will test a fixed dose of CAR‑NK cells (CL‑NK‑003) in adults with locally advanced, metastatic, or recurrent pancreatic cancer whose tumors show high eGR1 expression.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Changhai Hospital (Academic / other)
• Drugs / interventions: prednisone
• Locations: 1 site (Shanghai)
• Trial ID: NCT07425483 on ClinicalTrials.gov

What this trial studies

This single-center, open-label, first-in-human Phase 1 fixed-dose trial gives CL-NK-003 CAR-NK cells to adults with locally advanced, metastatic, or recurrent pancreatic cancer. Patients must have tumor membrane eGR1 expression >40% with intensity ≥2+ and at least one measurable lesion by RECIST 1.1, and must have failed or been intolerant of standard therapy. The primary focus is on safety and tolerability, with secondary collection of preliminary anti-tumor activity and biomarker data. Key exclusions include central nervous system involvement and prior adoptive cell therapy, and participants must meet baseline blood and organ-function requirements.

Who should consider this trial

Good fit: Adults 18–75 years with locally advanced, metastatic, or recurrent pancreatic cancer whose tumors are eGR1 membrane positive (>40% cells and ≥2+ intensity), with ECOG 0–2 and adequate blood and organ function are the intended candidates.

Not a fit: Patients whose tumors lack significant eGR1 expression, who have active central nervous system disease, poor organ function, or prior adoptive cell therapy are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this approach could offer a new targeted cell therapy option for patients with eGR1-positive pancreatic cancer.

How similar studies have performed: CAR-NK therapies have shown early safety and activity in blood cancers and promising preclinical results in solid tumors, but CAR-NK use specifically in pancreatic cancer remains largely untested in humans.

Eligibility criteria

Inclusion Criteria:

* 1\. Aged 18-75 years;2. 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;3. At least 1 measurable lesion according to RECIST 1.1;4. Have not received anti-tumor treatment for at least 4 weeks;5. ECOG performance status of 0-2;6. Estimated life expectancy more than 12 weeks;7. Hematology: neutrophils ≥ 1.5×10\^9/L, lymphocytes ≥ 0.8×10\^9/L, hemoglobin ≥ 100 g/L, and platelets ≥ 75 × 10\^9/L;8. Blood biochemistry: total bilirubin ≤ 2×ULN, alanine aminotransferase ≤ 3×ULN, aspartate aminotransferase ≤ 3×ULN, and creatinine clearance ≥ LLN (Cockcroft-Gault formula);9. Volunteer to participate in this clinical study and willing to sign written informed consent.

Exclusion Criteria:

* 1\. Evidence of central nervous system involvement;2. Have received adoptive cell therapy;3. Patients with any uncontrolled active infection, including but not limited to: HBV, HCV, HIV, or treponema pallidum serology positive;4. Vaccinated with a live attenuated vaccine within 3 months;5. History of immunodeficiency;6. Active autoimmune disease;7. Regular use of systemic corticosteroids within 2 weeks prior to screening at a dose exceeding prednisone 10 mg/day (or equivalent) on any day; 8. 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);9. Possible severe adverse events, allergy or other contraindications to drugs or its component under study;10. Pregnant or lactating women;11. History of neurological or psychological disorders;12. Not suitable to participate this clinical study judged by the investigator.

Where this trial is running

Shanghai

• Changhai Hospital — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Zhuan Liao — Changhai Hospital
• Study coordinator: Xuetao Cao

Conditions Pancreatic Cancer; pancreatic cancer; CAR-NK