Safety and Tolerability of NCP-IL-22BP mRNA in Advanced Solid Tumors

Официальное название

A Phase I, Open-Label, Single-Arm Study to Evaluate the Safety, Tolerability, and Preliminary Anti-Tumor Activity of Non-Cationic Peptide-IL-22BP mRNA (NCP-IL-22BP mRNA) in Patients With Advanced Malignant Solid Tumors

Обзор

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.

Вмешательства

• Биопрепарат 25 μg NCP-IL-22BP mRNA
  NCP-IL-22BP mRNA administered by intratumoral injection, 5 doses at weekly intervals
• Биопрепарат 50 μg NCP-IL-22BP mRNA
  NCP-IL-22BP mRNA administered by intratumoral injection, 5 doses at weekly intervals
• Биопрепарат 100 μg NCP-IL-22BP mRNA
  NCP-IL-22BP mRNA administered by intratumoral injection, 5 doses at weekly intervals

Первичные конечные точки

• Incidence of Dose-Limiting Toxicities [Срок оценки: From the first dose to 3 weeks post-dose. (approximately 3 weeks)]

Вторичные конечные точки (4)

• Objective Response Rate (ORR) [Срок оценки: 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.]
• Disease Control Rate [Срок оценки: 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.]
• Time to first complete remission, partial remission on treatment with IL-22BP preparation. [Срок оценки: 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.]
• Duration of Response [Срок оценки: 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.]

Критерии участия

Критерии включения

• Male or female patients aged ≥18 and ≤70 years
• 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)
• ECOG Performance Status score: 0-1
• Estimated life expectancy ≥3 months
• At least 28 days since prior chemotherapy, radiotherapy, or surgery
• At least 6 weeks since prior use of nitrosoureas or mitomycin C
• 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%
• Signed written informed consent

Критерии исключения

• Participation in another clinical drug trial within 4 weeks
• Tumor located adjacent to major blood vessels or trachea
• Poorly controlled cardiac conditions: NYHA class >2 heart failure, unstable angina, myocardial infarction within 1 year, or clinically significant arrhythmias requiring treatment
• Pregnant or breastfeeding women
• Active pulmonary tuberculosis, bacterial or fungal infection (≥Grade 2 per NCI-CTCAE v5.0); HIV infection, active HBV or HCV infection
• History of psychotropic substance abuse that cannot be discontinued, or mental disorders
• Active autoimmune disease or history of autoimmune disease (exceptions: vitiligo; childhood asthma in complete remission)
• Currently receiving immunosuppressive therapy
• History of drug abuse or known medical, psychological, or social conditions (e.g., alcoholism, drug addiction)
• Known allergy, hypersensitivity, or intolerance to IL-22BP or any excipient; history of severe allergic reactions to any drug, food, or vaccine
• Female subjects with pregnancy plans or male subjects whose partners have pregnancy plans from screening through 12 months after the last dose
• Any serious concomitant disease that, in the investigator's judgment, would jeopardize patient safety or ability to complete the study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• West China Hospital — Чэнду

Идентификаторы

NCT: NCT07562815 · 2026(936)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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