Vaccine demonstrates potential to delay relapse of KRAS-mutated pancreatic and colorectal cancers

A vaccine has shown potential to prevent relapse of KRAS-mutated pancreatic and colorectal cancers in patients who have previously undergone surgery, according to a Phase I trial led by researchers at the University of Texas MD Anderson Cancer Center. The results are published in Natural medicine.

In the trial, patients with pancreatic and colorectal cancer considered at high risk of relapse received a maximum of 10 doses of the ELI-002 vaccine targeting KRAS G12D and G12R mutations. T cell responses were observed 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.

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 with 4.01 months in the group with a below-median T-cell response level. This was a statistically significant improvement.

“Patients who have undergone surgery for pancreatic cancer are still at risk of disease relapse, even after completing chemotherapy. This is especially true for patients who test positive for circulating tumor DNA (ctDNA) , putting them at higher risk of pancreatic cancer relapse,” said lead researcher Shubham Pant, MD, associate professor of gastrointestinal medical oncology. “When these patients relapse, the disease is not curable, so this is certainly an area of ​​unmet need.”

The multicenter AMPLIFY-201 trial is evaluating ELI-002, a lymph node-targeted cancer vaccine designed to reduce the risk of these relapses by “training” T cells to recognize KRAS mutations, allowing them to identify and eliminate KRAS mutant cells. ELI-002 is also a commercially available vaccine, which means it does not need to be specially formulated for each individual. KRAS-mutated cancers account for about a quarter of all solid tumors, including 90% of pancreatic cancer patients, who most often carry the G12D mutation.

No patients experienced dose-limiting toxicities, cytokine release syndrome, or treatment-emergent adverse reactions of any kind above grade 3. The most common adverse reactions, regardless of grade, were fatigue (24%), injection site reaction (16%), and myalgia (12%).

Twenty-five patients participated in the trial, with a median age of 61 years. Of these, 84% were white, 8% were Asian, and two patients were of undeclared ethnicity. The patients were 60% women. All 25 had previously undergone surgery or another procedure designed for curative purposes, and seven had previously received radiation therapy.

“It’s early, but we’ve seen promising results that this vaccine could help many of these patients avoid relapses, which could increase survival,” Pant said. “It also showed a favorable safety profile, which is exciting.”

The results of this trial led to a Phase II trial that will begin later this year, with a new formulation of ELI-002 targeting additional KRAS mutations. Preliminary data from this trial were presented in 2023 at the American Society of Clinical Oncology (ASCO) Annual Meeting and at the American Association for Cancer Research (AACR) Special Conference on Pancreatic Cancer.