Experimental pancreatic cancer vaccine triggers immune response in nearly all trial patients
In a Mayo Clinic phase 2 trial of 144 people who had surgery for pancreatic cancer, a vaccine targeting mutations in the KRAS gene boosted immune responses in 89 of the 90 vaccinated patients who could be assessed. The catch: it missed its main goal, as time without relapse was not significantly longer than without the vaccine. A larger phase 3 trial is now being planned.
About nine in ten cases of the most common type of pancreatic cancer carry mutations in a gene called KRAS. A Mayo Clinic team has tested a vaccine that teaches the immune system to spot them, and in nearly every patient that first step worked: 89 of 90 assessable vaccinated patients showed stronger T-cell responses against mutated KRAS.
What matters most comes next, and this is the catch. The phase 2 trial, published in Nature Medicine, was mainly designed to lengthen the time before the cancer came back. With the vaccine, median disease-free survival was 23.8 months; without it, 21.2. The difference was not statistically significant.
An off-the-shelf vaccine
The trial enrolled 144 people with stage 1 to 3 pancreatic cancer who had already had surgery and chemotherapy and had no visible tumour on scans. 96 received the vaccine and 48 were observed. The vaccine is the same for everyone rather than made for each patient: it targets seven common KRAS mutations and is designed to reach the lymph nodes, where immune cells are trained.
“Historically, pancreatic cancer has been very difficult to treat with immunotherapy,” says oncologist Ben George, the lead author. “We’ve shown that we can teach the immune system to recognize these KRAS mutations.”
Clues for the next trial
In exploratory analyses, patients with the strongest response, more than nine times their starting level, stayed disease-free for longer. There were also signals in favour of the vaccine in people with no tumour DNA in their blood at the start and in those who had not had radiotherapy. Almost a year in, 95.5% of those assessed still had the response.
These are clues, not proof: overall survival data are not yet available. Mayo Clinic will use the results to design a larger phase 3 trial.
