The first clinical data from neoantigen vaccine companies have started to answer questions about the best way to quickly gauge whether patients are responding. The lessons include how to design combination trials that point to efficacy beyond checkpoint inhibition, and how to increase the rigor of ex vivo assays.
The idea that mutations from a patient's own tumor could be harnessed to treat cancer has been gaining steam for the last six years, with more than a dozen companies announcing personalized neoantigen vaccine programs. Each player has developed its own strategies for identifying neoantigens in tumors and delivering them as peptides, nucleic acids, or in microbial vectors (see "Neo Wave").
At least six have reported signals from Phase I trials. The results indicate the vaccines are capable of stimulating T cell responses in patients, but in the absence of long-term overall survival (OS) data, the connection between those responses and therapeutic benefit remains unclear.
"If you immunize, and there are pre-existing T cells there, it should be easy to see them straight away out of the blood," said Pact Pharma Inc. CEO Alex Franzusoff. "That doesn't mean that the T cells you got from immunization are actually relevant to the tumor."
"That doesn't mean that the T cells you got from immunization are actually relevant to the tumor."
Part of the challenge will be separating out the vaccines' effects from those of checkpoint inhibitors, given that the majority of Phase I programs