A Clinical Trial to Evaluate the Safety, Tolerability, and Preliminary Antitumor Activity of IMP3-saRNA (YMN-136) Vaccine in Patients With Advanced Non-Small Cell Lung Cancer
This is an open-label, single-arm, non-randomized, single-center, prospective phase 1 clinical trial. The study will evaluate the safety, tolerability, and preliminary antitumor activity of IMP3-saRNA (YMN-136) vaccine in patients with advanced non-small cell lung cancer. IMP3-saRNA (YMN-136) is a vaccine product prepared from IMP3 self-amplifying RNA and lipid nanoparticles. The study will enroll patients with histologically or cytologically confirmed non-small cell lung cancer who have failed standard treatment, are intolerant to standard treatment, or have refused standard treatment, and whose tumor tissue is positive for IMP3 expression. A total of 9 participants are planned to be enrolled. Participants will enter one of three dose groups sequentially: 50 micrograms, 100 micrograms, or 200 micrograms. Each dose group will include 3 participants. The study will use a 3+3 dose-escalation design. The vaccine will be administered by intramuscular injection. The immunization schedule includes 4 doses, with each dose given 3 weeks apart. The main purpose of the study is to assess safety and tolerability. Dose-limiting toxicity will be assessed from the first vaccination until 14 days after the third vaccination. Safety assessments will include adverse events, serious adverse events, physical examinations, vital signs, ECOG performance status, laboratory tests, 12-lead electrocardiogram, and echocardiography. The study will also preliminarily assess antitumor activity using RECIST version 1.1. Imaging assessments may include CT or MRI and whole-body bone scan. Additional exploratory evaluations may include blood and tumor tissue biomarker analyses, such as ctDNA, tumor markers, immune cell subsets, dendritic cell maturation, antigen-specific cytotoxic T cells, T-cell activation, antibody titers, PD-L1 expression, gene mutation analysis, and other immune-related tests.
• Patients aged at least 18 years at screening who voluntarily sign an ethics committee-approved informed consent form before any study procedure and agree to participate in this study.
• Patients with histologically or cytologically confirmed non-small cell lung cancer who have failed standard treatment, are intolerant to standard treatment, or have refused standard treatment, and whose tumor tissue is positive for IMP3 expression. The IMP3 pathological test result must be issued by the pathology department of this hospital or by a qualified pathology institution recognized by the study center. If a previous pathology report cannot confirm IMP3 status, IMP3 testing must be performed during screening, and only patients with positive results may be enrolled.
• Note:
⁃ Patients with EGFR-sensitive mutations must have failed third-line or later treatment, including failure of at least one EGFR-TKI.
⁃ Patients with ALK-positive disease must have failed third-line or later treatment, including failure of at least one ALK inhibitor.
⁃ Patients with ROS1-positive disease must have failed third-line or later treatment, including failure of at least one ROS1 inhibitor.
⁃ Patients with EGFR wild-type disease and no ALK or ROS1 positivity must have failed second-line or later treatment, including platinum-containing treatment.
• At least one measurable or evaluable lesion according to RECIST version 1.1.
• Eastern Cooperative Oncology Group performance status score of 0 to 2.
• Estimated life expectancy of at least 3 months.
• Adequate major organ function, with the following test results meeting the requirements within 7 days before treatment:
‣ Hemoglobin ≥80 g/L without blood transfusion within 14 days; absolute neutrophil count \>1.5 × 10\^9/L; white blood cell count ≥3.0 × 10\^9/L; platelet count ≥80 × 10\^9/L.
⁃ Total bilirubin ≤1.5 × upper limit of normal; alanine aminotransferase or aspartate aminotransferase ≤2.5 × upper limit of normal; in patients with liver metastasis, alanine aminotransferase or aspartate aminotransferase ≤5 × upper limit of normal.
⁃ Serum creatinine ≤1.5 × upper limit of normal or creatinine clearance estimated by the Cockcroft-Gault formula ≥60 mL/min.
⁃ Prothrombin time and international normalized ratio ≤1.5 × upper limit of normal, unless the patient is receiving warfarin anticoagulation.
⁃ Cardiac function: left ventricular ejection fraction ≥50%; QTcF interval ≤450 ms.
• Male patients with reproductive potential and female patients of childbearing potential voluntarily agree to use effective contraception, such as condoms, intrauterine devices, or spermicides, from signing the informed consent form until 6 months after completion of vaccination. Oral contraceptives are not allowed. Female cancer patients must have a negative pregnancy test and agree not to breastfeed during the study and for at least 18 months after administration of the investigational vaccine.
• The washout period for previous antitumor therapy must be no less than 4 weeks, and the washout period for molecular targeted therapy must be no less than 5 half-lives. Palliative radiotherapy must have been completed for at least 2 weeks; thoracic radiotherapy must have been completed for at least 3 months; and major surgery must have been completed with at least 4 weeks of recovery.