An experimental cancer vaccine developed by Elicio Therapeutics to target tumors with KRAS mutations has achieved good results in a Phase I trial in patients with residual pancreatic and colorectal cancer following earlier treatment.
As reported in Nature Medicine, the majority of patients in the study (84%) had a T cell response to the vaccine and those that did had reductions in tumor markers and DNA in the blood and an 86% reduction in the risk of having a relapse or dying.
The KRAS gene produces a protein involved in cell signaling. When mutated this gene can act as a cancer promoter and mutations in this gene are found in people with leukemias, colorectal, pancreatic and lung cancers.
Colorectal cancer and pancreatic ductal adenocarcinoma are the second and third most common causes of cancer-related death and both are associated with a poor prognosis. When these cancers have KRAS mutations, and tumor DNA and/or biomarkers are still found in the blood after initial therapy, they are often considered incurable.
“Patients who have undergone surgery for pancreatic cancer are still at risk for relapse of the disease, even after they finish chemotherapy. This is especially true for patients who are positive for circulating tumor DNA, which puts them at a higher risk for relapse,” said first author Shubham Pant, associate professor of gastrointestinal medical oncology at the University of Texas MD Anderson Cancer Center, in a press statement. “When these patients do relapse, the disease is not curable, so this is certainly an area of unmet need.”
Elicio licensed technology developed by scientists at MIT that can target KRAS mutated cancers and is delivered directly to the lymph nodes. The vaccine does not need to be tailored to individual patients and is able to lower the likelihood of cancer relapses by educating a patient’s immune T cells to recognize and kill cells with these mutations.
Following good preclinical results, a Phase I trial of the ELO-002 vaccine was launched in 25 patients (20 pancreatic and five colorectal cancer), who had residual KRAS mutated cancer after initial treatment.
The study team observed CD4+ and CD8+ T cell responses to the vaccine in 21 of 25 patients in the trial. Having a T cell response was linked with efficacy, as those with a response had a 76% versus a 10% reduction in tumor biomarkers and median relapse free survival was 4 months in those with a low T cell response (below median) versus more than 16 months in those with a better T cell response.
No serious adverse events above Grade 3 were seen such as cytokine release syndrome. The most common adverse events were fatigue, injection site reactions and myalgia.
“It’s early, but we saw some promising results that this vaccine may help many of these patients avoid relapse, which could increase survival,” Pant said. “It also showed a favorable safety profile, which is exciting.”
The company now plans to run a Phase II trial of the vaccine that will begin recruiting patients later this year.
