An experimental vaccine developed by German drug developer BioNTech showed early promise in a small study of people with pancreatic cancer, suggesting that personalized immunotherapy could offer a way to treat one of the deadliest types of tumors.
The results, published in the journal Nature on Wednesday, showed trial participants who responded to treatment with the vaccine went longer without their cancer returning after surgery than those who didn’t respond. The study was primarily designed to assess safety and participants’ immune responses, and “responder” analyses aren’t as rigorous a test as placebo-controlled comparisons.
Still, the data’s publication is the second time this year a drugmaker has detailed trial findings for a personalized cancer vaccine, after years of setbacks in the research field. In April, Moderna and partner Merck & Co. disclosed full results from a mid-stage trial of a cancer vaccine they’re developing for melanoma.
The studies also provide a sign that the biggest names in messenger RNA-based medicines may have a chance to deliver on expectations investors held for them in cancer treatment prior to their success developing COVID-19 vaccines. Roche paid $310 million seven years ago to collaborate with BioNTech on mRNA cancer vaccines.
BioNTech tested its cancer vaccine together with the immunotherapy Tecentriq, which is manufactured by Roche. The small trial was designed to detect whether the vaccine could stimulate T cells that target patient-specific mutated proteins on tumor cells. BioNTech said its vaccine can target up to 20 of these so-called neoantigens per patient.
Patients first underwent surgery to remove their tumors, then were treated with a single dose of Tecentriq, followed by eight infusions of BioNTech’s vaccine, called, autogene cevumeran. They then received a chemotherapy regimen called FOLFIRINOX. Of the 34 patients who were screened in the trial, 28 underwent surgery, 19 received Tecentriq, 16 got autogene cevumeran and 15 were treated with chemotherapy. Some patients dropped out for reasons that included disease progression, personal decisions to withdraw and an inability to manufacture the vaccine.
Researchers analyzed the vaccine’s effectiveness at 18 months in the 16 people who received it, eight of whom responded and eight of whom didn’t. The non-responders went a median of 13.4 months between their surgery and their cancer’s recurrence, while not enough of the responders had had their disease return to calculate a median figure. Researchers determined the risk of recurrence in the responders was 92% lower than among the non-responders.
Importantly, they found that patients’ T cell response persisted, lasting up to two years despite the follow-up chemotherapy. Half of the treated participants had T cells that were specific to at least one neoantigen. (The median number of neoantigens bound by T cells after vaccination was two, and the highest eight.)
Side effects were few overall, researchers said. One patient who received autogene cevumeran experienced fever and hypertension that qualified as “Grade 3,” or severe.
“Although a very small study, this trial demonstrates the ability of mRNA vaccines to elicit potent anti-tumor T cell responses that appear to create significant clinical benefit,” said Ira Mellman, vice president of cancer immunology at Roche’s Genentech division and an author on the paper, in an emailed statement. “That such benefit was seen in pancreatic cancer, a lethal disease that has thus far been refractory to any form of immunotherapy, makes the result all the more exciting.”
Mellman said the study also suggests the best use for cancer vaccines may be in the post-surgical setting, when patients and physicians are trying to keep disease from returning, rather than in primary treatment of tumors.
In an accompanying Nature editorial, Amanda Huff and Neeha Zaidi of Johns Hopkins University medical school wrote that the study “established the feasibility of using mRNA-based neoantigen vaccines for pancreatic cancer.”
Yet they cautioned that researchers need to determine why half of the people given the vaccine didn't respond.
The paper’s authors suggest some possible explanations. Non-responders had, on average, larger primary tumors. Five of the eight also had their spleens removed as part of their pancreatic cancer surgery, compared to two of the responders. Mice that have their spleens removed have weaker T cell responses to mRNA vaccines, they noted.
“That vaccines induced high magnitude T cell responses in 50% of patients may highlight the need for biomarkers to select optimal patients and tumors for this treatment,” they wrote.