Three-year follow-up data from Phase 1 trial shows persistence of immune response and delayed tumor recurrence in some pancreatic cancer patients after surgery

April 8, 2024 by No Comments

Three-year follow-up data from a Phase 1 trial of the individualized mRNA cancer vaccine candidate autogene cevumeran (also known as BNT122, RO7198457) in patients with resected pancreatic ductal adenocarcinoma (“PDAC”) continue to demonstrate T cell responses specific to the encoded neoantigens up to three years after administration. In 8 of 16 patients, autogene cevumeran induced high-magnitude T cells targeting individual neoantigens on the tumor. 98% of the T cells targeting individual neoantigens on the tumor and induced by autogene cevumeran were newly developed in that they were not detected in blood, tumors, and adjacent tissues prior to administration of the investigational treatment. Over 80% of the vaccine-induced neoantigen-specific T cells could still be detected up to three years post administration in patients with an immune response. These patients showed a prolonged median recurrence-free survival compared to non-responders. 6 of 8 patients with an immune response to autogene cevumeran remained disease free during the three-year follow-up period, while 7 of the 8 patients without an immune response to the treatment during the trial showed tumor recurrence.

The investigator-initiated, single center Phase 1 trial evaluated the safety of autogene cevumeran in sequential combination with the anti-PD-L1 immune checkpoint inhibitor atezolizumab and standard-of-care chemotherapy in 16 patients with resected PDAC. Data from the 1.5-year median follow-up were published in May 2023. The current data update includes a three-year median follow-up and was presented in a late-breaking oral presentation at the AACR Annual Meeting 2024 in San Diego, California, by principal investigator Vinod Balachandran, M.D., surgeon-scientist at Memorial Sloan Kettering Cancer Center and principal investigator of the study.

An ongoing open-label, multicenter, randomized Phase 2 trial, sponsored by Genentech in collaboration with BioNTech, was started in October 2023. The trial will investigate the efficacy and safety of adjuvant autogene cevumeran in combination with the anti-PD-L1 immune checkpoint inhibitor atezolizumab and chemotherapy compared with the current standard of care chemotherapy (mFOLFIRINOX) in patients with PDAC. The Phase 2 trial is currently enrolling patients at clinical trial sites in the United States, with additional sites planned to open globally. Autogene cevumeran is being jointly developed by BioNTech and Genentech and is currently being evaluated in three ongoing randomized Phase 2 clinical trials in adjuvant PDAC (as mentioned above), first-line melanoma, and adjuvant colorectal cancer.