Safety and Tolerability of AI-Designed Pan-Cancer Neoantigen mRNA Vaccine (PAN-NeoVax) in Advanced Solid Tumors

Официальное название

A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of an Artificial Intelligence-Designed Tumor mRNA Vaccine in Patients With Advanced or Metastatic 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 efficacy of PAN-NeoVax, an artificial intelligence (AI)-designed pan-cancer neoantigen mRNA vaccine delivered via lipid nanoparticles (LNP), administered by intratumoral injection in patients with advanced or metastatic 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 of basic immunization (first 4 doses at weekly intervals, fifth dose at 1 month after the fourth dose).

Вмешательства

• Биопрепарат PAN-NeoVax (25 μg)
  25 μg PAN-NeoVax administered by intratumoral injection; 5 doses of basic immunization (first 4 doses at weekly intervals, fifth dose at 1 month after the fourth dose).
• Биопрепарат PAN-NeoVax (50 μg)
  50 μg PAN-NeoVax administered by intratumoral injection; 5 doses of basic immunization (first 4 doses at weekly intervals, fifth dose at 1 month after the fourth dose).
• Биопрепарат PAN-NeoVax (100 μg)
  100 μg PAN-NeoVax administered by intratumoral injection; 5 doses of basic immunization (first 4 doses at weekly intervals, fifth dose at 1 month after the fourth dose).

Первичные конечные точки

• Number of Participants with DLT [Срок оценки: From the first dose to 3 weeks post-dose.]

Вторичные конечные точки (6)

• Objective Response Rate [Срок оценки: From the time when the patients were enrolled in the study until one month after the last dose 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 was injected.The time window was typically 2 months.]
• Time to First Response [Срок оценки: From the time when the patients were enrolled in the study until one month after the last dose 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 was injected.The time window was typically 2 months.]
• Progression - Free Survival(PFS) [Срок оценки: From the time when the patients were enrolled in the study until three months after the last dose was injected. The time window was typically 6 months.]
• Overall Survival(OS) [Срок оценки: From the time when the patients were enrolled in the study until six months after the last dose was injected. The time window was typically 8 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 (priority enrollment of advanced head and neck squamous cell carcinoma and malignant melanoma patients)
• 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 and willingness to comply with scheduled visits, treatment plans, laboratory tests, and other study requirements

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 supraventricular or ventricular arrhythmias requiring treatment or intervention
• 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 requiring no adult intervention; asthma requiring bronchodilator intervention is excluded)
• 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 PAN-NeoVax or any excipient; history of severe allergic reactions to any drug, food, or vaccine (including anaphylactic shock, allergic laryngeal edema, allergic dyspnea, allergic purpura, thrombocytopenic purpura, Arthus reaction)
• 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 · 2 центра

• West China Hospital — Чэнду
• The West China Hospital — Чэнду

Идентификаторы

NCT: NCT07560943 · 2026(826)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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