Researchers from the Memorial Sloan Kettering Cancer Center (MSKCC) have shown that an experimental investigational mRNA-based vaccine candidate shows potential to stimulate the immune system which may reduce the risk of pancreatic cancer returning after surgery. In new results from a Phase I trial, the candidate, autogene cevumeran, activated immune cells that persisted in some patients for up to three years after treatment.
Results of the trial were presented Sunday at the AACR Annual Meeting that will continue through April 10 in San Diego. Earlier positive results, published last May in Nature, showed that the vaccine was well tolerated and activated immune cells in half of the patients.
“Current treatment options for pancreatic cancer remain very limited, and only about 12% of patients survive five years after diagnosis,” said pancreatic cancer researcher Vinod P. Balachandran, MD, a member of the Human Oncology and Pathogenesis Program at MSKCC. “We are encouraged by our latest findings, which continue to support exploring autogene cevumeran as an approach to treat pancreatic cancer in the post-surgical, adjuvant setting.”
The candidate vaccine was developed via a collaboration between immunotherapy biotech BioNTech and Roche Group company Genentech. For this trial, every vaccine was custom-made to match the mutational profile of each patient’s tumor. The bespoke approach is intended to train the patients’ T cells to specifically recognize the proteins found in their individual pancreatic tumors as a means to activate the T cells to identify the cancer cells as foreign allowing it to be protective of cancer recurrence.
Following on the research published last year in Nature, the team has continued to follow patients to track their response to the vaccine. At this three-year median follow-up, the investigators continue to observe robust immune response in patients that was activated by the vaccine. Blood analysis of patients enrolled in the trial showed the 98% of the T cells that were specifically activated by autogene cevumeran were not found in patients prior to receiving the vaccine.
Further, in more than 80% of the patients, the vaccine-induced T cells remained in patients’ bodies from two to three years after being vaccinated. This persistence resulted in delayed disease recurrence and only two of the eight patients exhibiting immune response from the vaccine experience disease relapse during the follow-up period. In patients who did not respond to the vaccine, seven of eight saw their cancer return during in the ensuing three years. While these results are promising the investigators noted that they could not precisely determine whether the vaccine caused this delay in disease recurrence and will focus on this question in future work.
Meanwhile, Genentech and BioNTech are evaluating the efficacy and safety of autogene ceveumeran as an adjuvant therapy compared to the current standard regimen of chemotherapy, with the goal of the Phase II trial being a reduction in pancreatic cancer returning after the tumor is surgically removed. The trial aims to enroll a total of 260 patients at sites around the world, including MSKCC.
