Pancreatic Cancer
Conditions
Keywords
pancreatic cancer, CAR-NK
Brief summary
This is a single-center, open-label, first-in-human, dose-escalation study in patients with pancreatic cancer.
Detailed description
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.
Interventions
BIOLOGICALCL-NK-001
Dose level 1 (5 × 10\^8 cells); dose level 2 (15 × 10\^8 cells); dose level 3 (30 × 10\^8 cells); additional dose levels (investigator's discretion).
Sponsors
Changhai Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 18-70 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. 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); 8. Possible severe adverse events, allergy or other contraindications to drugs or its component under study; 9. Pregnant or lactating women; 10. History of neurological or psychological disorders; 11. Not suitable to participate this clinical study judged by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with change from baseline in QT/QTc interval in electrocardiogram | 42 days of first infusion | Safety |
| Dose-limiting toxicity (DLT) | 42 days of first infusion | Safety |
| Maximum tolerated dose (MTD) | 42 days of first infusion | Tolerability |
| Treatment-emergent adverse event (TEAE) and treatment-emergent serious adverse event (TESAE) | 42 days of first infusion | Safety |
| Number of participants with abnormal clinical laboratory parameters reported as TEAE | 42 days of first infusion | Safety |
| Number of participants with abnormal vital signs reported as TEAE | 42 days of first infusion | Safety |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | 42 days of first infusion | Efficacy |
| Disease control rate (DCR) | 42 days of first infusion | Efficacy |
| Progression-free survival (PFS) | 6 months | Efficacy |
| Overall survival (OS) | 6 months | Efficacy |
| Patient-reported quality of life (QoL) | 42 days of first infusion | Measured by the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (EORTC QLQ-C30) |
| Patient-generated subjective global assessment (PG-SGA) | 42 days of first infusion | Nutritional status measurement with a medical history section assessed by patients and a physical assessment section assessed by medical staff |
Countries
China
Contacts
Primary ContactYanfang Liu, MD PhD
Outcome results
None listed