ASCO 2022 | Phase I trial of mRNA neoantigen vaccines for pancreatic cancer

Vinod P. Balachandran, MD, Memorial Sloan Kettering Cancer Center, New York, NY, provides an overview of the investigator-initiated, single-center, Phase I trial of adjuvant autogene cevumeran, an individualized mRNA neoantigen vaccine, for pancreatic ductal adenocarcinoma (PDAC). Each individualized vaccine contains 20 neoantigens identified from resected PDACs via next-generation sequencing (NGS) and bioinformatic neoantigen discovery. After surgery, patients received atezolizumab, autogene cevumeran and modified FOLFIRINOX. The primary endpoint was safety and additional endpoints included feasibility, vaccine response and recurrence-free survival (RFS). A total of 19 patients underwent surgery followed by atezolizumab with no patients experiencing adverse events of grade 3 or more. 84% of patients received the vaccine at a median of 9.4 weeks following surgery. 6% developed a vaccine-related grade 3 fever and hypertension. 94% received FOLFIRINOX. In 50% of patients, autogene cevumeran expanded polyclonal, IFNg-producing neoantigen-specific CD8+ T cells from undetectable levels to large fractions of all blood T-cells. Vaccine responders had a longer RFS compared to non-responders at a median follow-up of 15 months. In conclusion, autogene cevumeran is reported to be safe and feasible to individually manufacture. Further trials are warranted to explore this vaccine in PDAC. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.