Cancer
Conditions
Keywords
cancer, biotherapy
Brief summary
This is a phase I, open-label, single-arm, single-center, dose-escalation study to evaluate the safety, tolerability, and preliminary anti-tumor activity of NCP-IL-22BP mRNA, a non-cationic peptide-delivered mRNA encoding interleukin-22 binding protein (IL-22BP), administered by intratumoral injection in patients with advanced malignant solid tumors who have failed second-line therapy. The study employs a classical "3+3" dose-escalation design with three dose levels (25 μg, 50 μg, and 100 μg mRNA). Each subject will receive 5 doses at weekly intervals. The primary objective is to assess the safety and tolerability of NCP-IL-22BP mRNA, and the secondary objective is to evaluate its preliminary anti-tumor activity.
Interventions
BIOLOGICAL25 μg NCP-IL-22BP mRNA
NCP-IL-22BP mRNA administered by intratumoral injection, 5 doses at weekly intervals
BIOLOGICAL50 μg NCP-IL-22BP mRNA
NCP-IL-22BP mRNA administered by intratumoral injection, 5 doses at weekly intervals
BIOLOGICAL100 μg NCP-IL-22BP mRNA
NCP-IL-22BP mRNA administered by intratumoral injection, 5 doses at weekly intervals
Sponsors
West China Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients aged ≥18 and ≤70 years 2. Histopathologically confirmed advanced recurrent/metastatic malignant solid tumors that have failed second-line therapy with no standard treatment options available (e.g., advanced soft tissue sarcoma, head and neck squamous cell carcinoma, malignant melanoma) 3. ECOG Performance Status score: 0-1 4. Estimated life expectancy ≥3 months 5. At least 28 days since prior chemotherapy, radiotherapy, or surgery 6. At least 6 weeks since prior use of nitrosoureas or mitomycin C 7. Adequate organ function within 14 days prior to enrollment: * Hemoglobin ≥90 g/L (no blood transfusion within 14 days) * Absolute neutrophil count \>1.5×10⁹/L * Platelet count ≥80×10⁹/L * Total bilirubin ≤1.5×ULN * ALT or AST ≤2.5×ULN (≤5×ULN if liver metastases present) * Creatinine clearance ≥60 mL/min (Cockcroft-Gault formula) * Left ventricular ejection fraction (LVEF) ≥50% 8. Signed written informed consent
Exclusion criteria
1. Participation in another clinical drug trial within 4 weeks 2. Tumor located adjacent to major blood vessels or trachea 3. Poorly controlled cardiac conditions: NYHA class \>2 heart failure, unstable angina, myocardial infarction within 1 year, or clinically significant arrhythmias requiring treatment 4. Pregnant or breastfeeding women 5. Active pulmonary tuberculosis, bacterial or fungal infection (≥Grade 2 per NCI-CTCAE v5.0); HIV infection, active HBV or HCV infection 6. History of psychotropic substance abuse that cannot be discontinued, or mental disorders 7. Active autoimmune disease or history of autoimmune disease (exceptions: vitiligo; childhood asthma in complete remission) 8. Currently receiving immunosuppressive therapy 9. History of drug abuse or known medical, psychological, or social conditions (e.g., alcoholism, drug addiction) 10. Known allergy, hypersensitivity, or intolerance to IL-22BP or any excipient; history of severe allergic reactions to any drug, food, or vaccine 11. Female subjects with pregnancy plans or male subjects whose partners have pregnancy plans from screening through 12 months after the last dose 12. Any serious concomitant disease that, in the investigator's judgment, would jeopardize patient safety or ability to complete the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicities | From the first dose to 3 weeks post-dose. (approximately 3 weeks) | Number and percentage of subjects experiencing DLT during the first treatment cycle (from first dose through 7 days after the fifth dose), assessed per CTCAE v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From the time when the patients were enrolled in the study until one month after the last dose of the IL-22BP was injected.The time window was typically 2 months. | Proportion of subjects achieving complete response (CR) or partial response (PR) per RECIST v1.1 |
| Disease Control Rate | From the time when the patients were enrolled in the study until one month after the last dose of the IL-22BP was injected.The time window was typically 2 months. | Proportion of subjects achieving CR, PR, or stable disease (SD) per RECIST v1.1 |
| Time to first complete remission, partial remission on treatment with IL-22BP preparation. | From the time when the patients were enrolled in the study until one month after the last dose of the IL-22BP was injected.The time window was typically 2 months. | Complete Response: All target lesions disappear, no new lesions emerge, and tumor markers return to normal. This means that, from the perspective of imaging and relevant examinations, the tumor has completely vanished, and the patient's condition has achieved the most ideal improvement. For example, in the treatment of lymphoma, if enlarged lymph nodes completely disappear as detected by imaging examinations such as PET-CT, and relevant tumor markers in the blood also return to normal, it can be judged as a complete response. Partial Response: The sum of the maximum diameters of target lesions is reduced by ≥ 30%, and no new lesions appear. Taking lung cancer as an example, if the sum of the maximum diameters of lung tumors is reduced by more than 30% after treatment and no new tumor lesions are detected, it is in a partial response state. This situation indicates that the tumor responds to the treatment and the patient's condition is under a certain degree of control. |
| Duration of Response | From the time when the patients were enrolled in the study until one month after the last dose of the IL-22BP was injected.The time window was typically 2 months. | It is defined as the time between the first confirmation of complete response, partial response and the first disease progression or death from any cause. |
Countries
China
Contacts
CONTACTXingchen Peng
PRINCIPAL_INVESTIGATORXingchen Peng
The West China Hospital
Outcome results
None listed