clinical study of personalized mrna vaccine encoding neoantigen in patients with advanced esophageal cancer and non-small cell lung cancer

Conditions: Esophageal Cancer; Non Small Cell Lung Cancer

Summary: a single arm, open-label pilot study is designed to determine the safety, tolerability and effectiveness of personalized mrna tumor vaccine encoding neoantigen in patients with advanced esophageal cancer and non-small cell lung cancer

primary objectives: assessing the safety and tolerability of mrna personalized tumor vaccines encoding neoantigen for unresectable or metastatic advanced esophageal and non-small cell lung cancers with standard treatment failure or no standard treatment. secondary objectives: preliminary observation of the efficacy of mrna personalized tumor vaccines encoding neoantigen for unsurgically resected or metastatic advanced esophageal and non-small cell lung cancers with standard treatment failure or no standard treatment. time of tumor progression (ttp); disease control rate (dcr); objective remission rate (orr); overall survival (os).

Eligibility criteria:
inclusion criteria: * aged between 18 and 75 (including both ends), with no gender limit; * the primary lesion was confirmed by histopathology or cytology as esophageal carcinoma (ⅲc (t4bnanym0, tanyn3m0), and stage ⅳ) or non-small cell lung cancer (stage ⅲb-ⅳ). * patients who have metastatic or locally advanced tumor but failed instandard treatments or not suitable for standard treatments; * according to recist (v1.1), the efficacy evaluation criteria for solid tumors, there is at least one measurable lesion. * participants with performance scale (ps) of 0 or 1 on the eastern cooperative oncology group (ecog) ps * participants must have at least 1 lesion amenable to the mandatory fresh tumor biopsy at study entry * fertile patients must agree to use a reliable contraceptive methods (hormonal or barrier methods or abstinence) during the trial and for at least 12 weeks after the last treatment; * the subject voluntarily participates and signs icf (informed consent forms). exclusion criteria: * any clinical research drugs, anti-cancer monoclonal antibodies, anti-cancer therapeutic vaccines, immunostimulants (such as il-2) or using previous investigational drugs within 7 days of the first treatment with mrna-personalized tumor vaccine or carrelizumab. * patients who have allergies or previous history of biological drug allergy; * patients who are in pregnant or breast-feeding; * patients who are expected to survive less than 3 months during the screening period; * tumor mutation load (tmb) is less than 2.0/mb or tumor neogenic antigen load (tnb) is less than 0.5/mb or the number of predicted neoantigen is less than 3; * patients who underwent major surgery or suffered significant trauma within 4 weeks prior to the enrollment (blood collection), or who are expected to undergo major surgery during the study period; * patients with symptoms of brain metastases (patients with stable brain metastases can be included) * extensive lung metastases from tumors, causing breathing difficulties; * patients who have tumors close to large blood vessels or nerves; * a history of severe cardiovascular and cerebrovascular diseases, including but not limited to ventricular arrhythmia requiring clinical intervention; acute coronary syndrome, myocardial infarction, congestive heart failure, stroke or other grade iii and above cardiovascular events within 6 months; new york heart association (nyha) cardiac function grade≥grade ii or left ventricular ejection fraction (lvef) \ 150 mmhg and diastolic blood pressure\> 90 mmhg); * patients with active ulcers and gastrointestinal bleeding; * patients with clinically confirmed autoimmune disease have received systemic treatment in the past 2 years; hiv, hcv positive; hbv-dna≥1×103 copies/ml (or 2×102 iu/ml); acute ebv or cmv virus infection; * patients with previous history of non-infectious pneumonia requiring steroid therapy or acute lung cancer; * participants with a history of interstitial lung disease; * patients who have a history of organ transplantation or are waiting for organ transplantation; * have any uncontrolled active infection; * immunosuppressed subjects, including those with known immunodeficiency; those who are currently using steroids systemically (except those who are using inhaled steroids recently or currently); * skin diseases (such as psoriasis) may prevent intradermal vaccines from reaching the target area; * who have received chemotherapy, biotherapy, radiotherapy, endocrine therapy, targeted therapy and other tumor treatments, or other experimental drug treatments, or surgery (excluding diagnostic biopsy) within 7 days prior to the first administration of mrna tumor vaccine treatment; * adverse effects from previous antitumor therapy have not recovered referred to ctcae (v5.0) rating ≤1 (except hair loss); * the investigator evaluates that the subject is unable or unwilling to comply with the requirements of study protocol.

Keywords: mrna cancer vaccine cancer vaccine tumor vaccine nsclc esophageal cancer