Personalized neoantigen vaccine for advanced gastric, esophageal, and liver cancer

A Dose-Escalation and Dose-Expansion Study Evaluating the Safety and Efficacy of Personalized Neoantigen Vaccine in Advanced Gastric Cancer, Esophageal Cancer and Liver Cancer

This study is testing a personalized cancer vaccine to see if it can safely help people with advanced gastric, esophageal, and liver cancer.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The Affiliated Hospital of the Chinese Academy of Military Medical Sciences (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Beijing, Beijing)
• Trial ID: NCT05192460 on ClinicalTrials.gov

What this trial studies

This trial investigates the safety and efficacy of a personalized mRNA neoantigen tumor vaccine in patients with advanced gastric cancer, esophageal cancer, and liver cancer. It is an open-label, single-arm exploratory study that includes a dose escalation phase followed by a dose expansion phase, where the vaccine may be combined with PD-1/L1 therapy. The study aims to evaluate the tolerability of the vaccine and preliminarily assess its effectiveness in treating these advanced cancers. Participants will be closely monitored for safety and efficacy outcomes throughout the trial.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with advanced gastric, esophageal, or liver cancer who have failed standard treatments and have measurable disease.

Not a fit: Patients with early-stage cancer or those who have not yet undergone standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a novel treatment option for patients with advanced cancers that have not responded to standard therapies.

How similar studies have performed: While the use of neoantigen vaccines is a promising area of research, this specific approach is still exploratory and has not been widely tested in similar trials.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily signed and provided formal informed consent;
2. Male and female patients aged 18-75 years (inclusive);
3. Expected survival ≥ 3 months;
4. Subject with advanced gastric cancer, esophageal cancer and liver cancer proved by histopathology or cytology and who have failed to respond to standard treatment;
5. At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors RECIST v1.1 (see Appendix 4, Response Evaluation Criteria in Solid Tumors) (i.e., mass ≥ 10 mm in diameter and malignant lymph node ≥ 15 mm in short diameter on enhanced spiral CT ≤ 5 mm);
6. ECOG performance status score of 0 \~ 2;
7. Treatment with other antineoplastic agents (e.g., chemotherapy, hormonal therapy, immunotherapy, antibody therapy, radiotherapy) for more than 5 half-lives of this agent or more than 4 weeks from baseline (whichever is shorter) during the baseline period ;
8. The organ function level must meet the following requirements (no blood transfusion or blood products, no hematopoietic stimulating factors, no albumin or blood products): absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L, platelet count (PLT) ≥ 75 × 10\^9/L, hemoglobin (Hb) ≥ 90 g/L; serum total bilirubin (TBIL) ≤ 1.5 ×ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×ULN (if there is liver metastasis, total bilirubin ≤ 3 ×ULN, AST, ALT ≤ 5 ×ULN are allowed); Note: These laboratory tests may only be repeated once if the investigator deems it necessary (the reason for retest must be documented). If the criteria are met after retest, the laboratory parameter can be considered qualified.
9. Premenopausal women of childbearing potential must have a negative pregnancy test within 7 days prior to initiation of treatment and be non-lactating; women of non-childbearing potential are not required to have a pregnancy test and contraception unless participants are 50 years of age or older, have not used hormonal therapy and have been amenorrheic for at least 12 months, or have been surgically sterilized. All subjects (male or female) should use adequate barrier contraception throughout treatment and for 3 months after the end of treatment.

Exclusion Criteria:

1. Subject who need to receive systemic application of anti-allergic drugs for a long time, or have a history of life-threatening allergic reactions to any vaccine or drug;
2. Symptomatic or rapidly progressive central nervous system metastases. Patients with extensive lung metastases resulting in dyspnea; patients with tumors close to or invading major blood vessels or nerves;
3. New cerebrovascular accident (including ischemic stroke, hemorrhagic stroke, and transient ischemic attack) within 6 months before screening;
4. Subject with acute myocardial infarction within 6 months before screening, or uncontrolled angina, uncontrolled arrhythmia, severe heart failure (see Appendix 3, New York Heart Association Heart Failure Classification Criteria NYHA Class ≥ III) and other cardiovascular diseases;
5. Subject who have received treatment with immunomodulatory drugs 4 times before the first vaccination day (D1), including but not limited to: IL-2, CTLA-4 inhibitors, CD40 agonists, CD137 agonists, IFN-α (except for high-risk surgical subjects who use IFN-α as adjuvant therapy, if IFN-α treatment is stopped 4 times before this trial);
6. Subject with a history of renal insufficiency, serum creatinine level greater than 1.5 times the upper limit of normal;
7. Subject who received blood transfusion, erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) before baseline;
8. Subject with skin diseases (e.g., psoriasis) at baseline that may prevent the intradermal injection of vaccine into the target area;
9. Subject still suffer from adverse reactions (except alopecia and platinum-induced neurotoxicity ≤ grade 2) that have not been restored to CTCAE version 5.0 grade ≤ 1 after previous anti-tumor treatment during the screening period;
10. Concomitant use of steroid hormone drugs (tumor or non-tumor related diseases) is required; however, topical application (not applied to the vaccination site) or inhaled steroid drugs are required;
11. Subject has an active infection or uncontrollable infection (except for simple urinary tract infection or upper respiratory tract infection) requiring systemic treatment; subjects with positive human immunodeficiency virus antibody, hepatitis B surface antigen and/or hepatitis B core antibody and positive hepatitis B virus deoxyribonucleic acid \> 103 copies/mL, hepatitis C virus antibody, Treponema pallidum-specific antibody in virological monitoring during the screening period;
12. Hypertension poorly controlled on treatment (defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg);
13. Subject with other malignant tumors within 5 years before the screening period, except for cervical carcinoma in situ, breast carcinoma in situ and cutaneous basal cell carcinoma that have received appropriate treatment and met the recovery criteria;
14. Subject with a history of autoimmune diseases \[such as, but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (hypothyroidism without clinical symptoms or hypothyroidism caused by chemoradiotherapy can be included), subjects with vitiligo or recovered asthma can be included without any intervention, and subjects with asthma requiring bronchodilators for medical intervention cannot be included\];
15. Subject with active ulcer or gastrointestinal bleeding during the screening period;
16. Subject who has previously received similar therapeutic tumor vaccines;
17. Subject with congenital or acquired immunodeficiency;
18. Subject still participating in other clinical trials and not enrolled at the screening period;
19. Subject has a known alcohol or drug addiction;
20. Subject who is unable or unwilling to comply with the study protocol due to potential health, mental or social conditions in the opinion of the investigator;
21. Other conditions that, in the opinion of the investigator, would make participation in this study inappropriate.

Where this trial is running

Beijing, Beijing

• PLA General Hospital — Beijing, Beijing, China (Recruiting)

Study contacts

• Principal investigator: Jianming Xu, Dr. — Chinese PLA General Hospital
• Study coordinator: Jianming Xu, Dr.

Conditions Gastric Cancer; Esophageal Cancer; Liver Cancer; Vaccine; Neoantigen