A phase 2 clinical trial led by a researcher at the Mayo Clinic found that camupepimut generated a strong immune response against mutated KRAS in nearly all patients with KRAS-mutated pancreatic cancer who received it. However, the study found no statistically significant difference in disease-free survival between the vaccine and control groups, and the vaccine’s benefits remain unclear.
The randomised trial enrolled 144 patients with KRAS-mutated pancreatic cancer who had undergone surgery and chemotherapy and showed no visible signs of cancer on imaging. Of these, 96 received the vaccine while 48 served as controls.
Pancreatic cancer can recur in up to 80 percent of patients, by some estimates. About 90 percent of pancreatic ductal adenocarcinomas, the most common type of pancreatic cancer, carry mutations in the KRAS gene that can help the cancer survive and thrive. Immunotherapy has historically been difficult to use against this disease.
Camupepimut is designed to teach the body's immune cells to recognise and attack cells expressing seven common KRAS mutations. Of the 90 vaccinated patients who could be assessed, 98.9 percent developed increased T-cell responses against mutated KRAS after vaccination. In more than 80 percent of patients, the T-cell response was more than nine times greater than before vaccination.
"Historically, pancreatic cancer has been very difficult to treat with immunotherapy," said first author and medical oncologist Ben George. "What is encouraging is that we were able to generate a strong immune response against KRAS mutations in nearly every patient we evaluated."
An exploratory analysis suggested that patients with greater immune responses appeared to have longer disease-free survival. The authors argue that the results provide a proof-of-concept for the vaccine’s potential clinical benefit.
"We've shown that we can teach the immune system to recognize these KRAS mutations," George said. "The next step is finding out whether doing that can change the course of the disease for patients."
The findings are published in Nature Medicine. A planned phase 3 trial will test additional booster doses and may test combinations with other cancer treatments. Separately, a personalised mRNA vaccine for pancreatic cancer is also in clinical trials; researchers said that, as of this year, seven patients whose immune systems mounted a response to the vaccine were alive and well.
Analysis
Why This Matters
- Pancreatic cancer has one of the lowest survival rates of any major cancer, and effective treatments are urgently needed.
- The trial demonstrates that a vaccine can reliably provoke a strong immune response against a common driver mutation, a hurdle that has stymied many immunotherapy approaches.
- Although the vaccine has not yet shown a survival benefit, the immune response provides a foundation for further refinement and combination strategies.
Background
Pancreatic cancer often recurs even after aggressive surgery and chemotherapy, driven in large part by KRAS mutations that help tumours evade the body's defences. Previous attempts to use immunotherapy have largely failed in this cancer type. Camupepimut targets the lymph nodes to train T cells to attack cells carrying seven specific KRAS mutations. The phase 2 trial, while not proving efficacy, marks one of the few times such a targeted vaccine has generated measurable immune responses in nearly all patients.
Key Perspectives
- Researchers (led by Ben George): Caution that the immune response is promising but does not yet translate into improved disease-free survival; the next step is to determine whether the immune attack can alter the disease course.
- Trial data: The absence of a statistically significant survival difference between groups tempers the enthusiasm, though exploratory analyses hint at a possible benefit for those with the strongest responses.
What to Watch
- Results of the phase 3 trial, which will include additional booster doses and may test combination regimens.
- Whether the vaccine can be combined with checkpoint inhibitors or other immunotherapies to enhance its effect.
- Progress of personalised mRNA vaccines for pancreatic cancer, which have shown encouraging early results in a small group of patients.
Checked
12 claims in this story checked against 1 source: 11 supported.
Show each claim
- SupportedThe vaccine triggered an immune response in nearly all patients in the early trial.ScienceAlert: “In a randomized phase 2 trial, nearly every patient who received this vaccine developed an immune response against a mutated gene called KRAS.”
- SupportedBen George said, “Historically, pancreatic cancer has been very difficult to treat with immunotherapy,” and “What is encouraging is that we were able to generate a strong immune response against KRAS mutations in nearly every patient we evaluated.”ScienceAlert: “"Historically, pancreatic cancer has been very difficult to treat with immunotherapy," explains first author and medical oncologist Ben George. "What is encouraging is that we were able to generate a strong immune response against KRAS mutations in nearly every patient we evaluated."”
- SupportedGeorge said, “We've shown that we can teach the immune system to recognize these KRAS mutations,” and “The next step is finding out whether doing that can change the course of the disease for patients.”ScienceAlert: “"We've shown that we can teach the immune system to recognize these KRAS mutations," George says . "The next step is finding out whether doing that can change the course of the disease for patients."”
- SupportedThe trial found no statistically significant difference in disease-free survival between the vaccine and control groups.ScienceAlert: “Importantly, there was no statistically significant difference in disease-free survival between the two groups.”
- SupportedThe vaccine’s benefits remain unclear.ScienceAlert: “Beyond that, however, its benefits are unclear.”
- SupportedThe phase 2 trial enrolled 144 patients; 96 received the vaccine and 48 were controls.ScienceAlert: “The phase 2 trial included 144 patients who had been treated for KRAS-mutated pancreatic cancer with surgery and chemotherapy. When they started the trial, none of these patients showed visible signs of cancer in imaging tests. George and colleagues randomly assigned 96 of these patients to receive the vaccine, while another 48 served as controls.”
- SupportedPancreatic cancer can recur in up to 80 percent of patients, by some estimates.ScienceAlert: “By some estimates, malignant tumors in the pancreas can recur in up to 80 percent of patients.”
- SupportedAbout 90 percent of pancreatic ductal adenocarcinomas carry KRAS mutations.ScienceAlert: “Mutations in KRAS are found in about 90 percent of pancreatic ductal adenocarcinomas, which is the most common type of pancreatic cancer.”
- SupportedOf the 90 vaccinated patients who could be assessed, 98.9 percent developed increased T-cell responses against mutated KRAS.ScienceAlert: “Of the 90 patients who received this medicine and could be assessed, 98.9 percent developed increased T-cell responses against mutated KRAS.”
- SupportedIn more than 80 percent of patients, the T-cell response was more than nine times greater than before vaccination.ScienceAlert: “In more than 80 percent of patients, the T-cell response was more than nine times greater than before vaccination.”
- Partly supportedCamupepimut is designed to teach immune cells to recognise and attack cells expressing seven common KRAS mutations.ScienceAlert: “The novel vaccine is called camupepimut, and it is designed to teach the body's immune cells to recognize and attack cancer cells that express seven common mutations in the KRAS gene.”
- SupportedAn exploratory analysis suggested that patients with greater immune responses appeared to have longer disease-free survival.ScienceAlert: “In an exploratory analysis, patients with greater immune responses to the vaccine appeared protected with longer disease-free survival times.”
