A new vaccine has shown potential to prevent relapse of pancreatic and colorectal cancers that are caused by a common genetic mutation, according to a Phase I trial. The vaccine, called ELI-002, targets the KRAS mutation, which is found in about a quarter of all solid tumors and 90% of pancreatic cancer patients. The trial, led by researchers at The University of Texas MD Anderson Cancer Center, was published in Nature Medicine.
How the vaccine works
ELI-002 is a lymph node-targeted cancer vaccine that aims to lower the likelihood of cancer relapse by “training” the immune system to recognize and eliminate KRAS-mutant cells. The vaccine consists of two components: a synthetic peptide that mimics the KRAS mutation and an adjuvant that enhances the immune response. The vaccine is injected into the skin, where it travels to the lymph nodes and activates T cells, the white blood cells that fight infections and cancer.
What the trial found
The trial enrolled 25 patients with pancreatic and colorectal cancer who had previously undergone surgery or another procedure designed to be curative, but were still at high risk of relapse. These patients had either detectable levels of circulating tumor DNA (ctDNA), a biomarker of residual cancer, or high-risk features such as lymph node involvement or positive surgical margins. The patients received a maximum of 10 doses of the vaccine over six months, at different dose levels ranging from 0.1 mg to 10 mg.
The trial found that the vaccine was safe and well-tolerated, with no dose-limiting toxicities, cytokine release syndrome, or any treatment-emergent adverse events above Grade 3. The most common side effects were fatigue, injection site reaction, and muscle pain.
The trial also found that the vaccine induced T cell responses in 84% of all patients and in 100% of those in the two highest dose cohorts, including those who received the recommended Phase II dose of 10 mg. The T cell responses were specific to the KRAS mutation and were not seen in healthy volunteers who received the vaccine.
The T cell responses were predictive of reductions in tumor biomarkers and ctDNA clearance, and they correlated with an 86% reduction in risk of relapse or death. For patients above the median T cell response level, median recurrence-free survival had not yet been reached, compared to 4.01 months in the group with a T cell response level below the median. This was a statistically significant improvement.
Why this is important
Pancreatic and colorectal cancers are among the deadliest cancers, with low survival rates and limited treatment options. Patients who have undergone surgery for these cancers are still at risk for relapse, especially if they have ctDNA in their blood, which indicates the presence of residual cancer cells. When these patients relapse, the disease is not curable, so preventing relapse is a crucial goal.
The vaccine is the first of its kind to target the KRAS mutation, which is one of the most common and challenging drivers of cancer. The mutation makes cancer cells resistant to many therapies and immune evasion. The vaccine offers a novel way to harness the power of the immune system to fight cancer and potentially improve outcomes for patients with KRAS-mutated cancers.
The researchers are planning to conduct a Phase II trial to further evaluate the efficacy and safety of the vaccine in patients with pancreatic and colorectal cancer. They are also exploring the possibility of combining the vaccine with other therapies, such as chemotherapy, immunotherapy, or targeted therapy, to enhance the anti-tumor effect. The vaccine may also be applicable to other types of cancers that harbor the KRAS mutation, such as lung, ovarian, and endometrial cancers.