Phase I trial of personalized mRNA vaccine encoding neoantigen in patients with advanced digestive system neoplasms.

e15269 Background: Cancer cells have characteristics of genetic instabilities and accumulate somatic mutations rapidly which could produce tumor specific antigens (TSAs) called as neoantigens. As the cancer vaccine based on TSAs has potential to treat the disease, personalized neoantigen-based immunotherapies are emerging. We report for the first time that vaccines are used to treat advanced digestive system neoplasms. Methods: In this single-arm, open-label, first-in-human phase I pilot study (NCT03468244) to investigate the feasibility, safety, immunogenicity and clinical activity of personalized mRNA vaccine. Patients with advanced digestive system neoplasms received up to 20 stimulatory synthetic long peptides vaccine at a dose of 0.2 mg on days 1 and 0.8mg on days 2, administered subcutaneously of every 3 weeks(Q3W) for 12 weeks. Patients was treated with standard treatments according to NCCN guideline simultaneously. Adverse Event (AE) grade categorization is according to CTCAE 4.0, and tumor response was assessed per RECIST 1.1. Immune factors and ELISPOT assay were examined every 3 weeks after vaccination. Results: As of February 1st, 2020, three patients (52yrs, 47yrs and 52yrs; ECOG PS: 0) with advanced rectal, colon and gastric cancer completed the vaccine therapy for 3-4 cycles. There were no serious adverse events, treatment-related death or severe neurotoxicity occurred in the study. The most common treatment-emergent adverse event (TEAE) was erythema at injection sites in three patients. Vaccine combined standard treatments treatment was associated with G3/4 hematological side effects: leucopenia (18%); neutropenia (9%); anemia (0); thrombocytopenia (18%). Blood samples for immune monitoring (ELISPOT and intracellular cytokine staining [ICS]) were collected pre-dose and at weeks 3 and 12. The level of IL-1β, IL-2 receptor, IL-6, IL-8, IL-10, and TNF-α increased for all patients. Especially, IL-8 and IL-2R increased significantly for more than 800 times in the patient with rectal cancer and more than 4 times in the patient with gastric cancer after injection, respectively. The PFS were 3.2, 3.0 and 3.0 months and the OS were 9.1, 6.0 and 7.8 months, respectively. Best response was 2 SD and 1 PD. Conclusions: This clinical study indicated that personalized mRNA vaccine may be safe and could activate immune response in vivo which is convinced by ELISPOT assay in vitro. Further studies are indicated to explore the personalized mRNA vaccine in gastrointestinal cancer. Clinical trial information: NCT03468244 .