A novel vaccine may be effective at preventing relapse in patients with KRAS-mutated pancreatic and colorectal cancers, according to a recent study published by Pant et al in Nature Medicine.
Background
KRAS-mutated cancers make up about 25% of all solid tumors, including 90% of pancreatic cancer cases.
The novel lymph node–targeted ELI-002 vaccine was designed to reduce the likelihood of relapse by training T cells to recognize KRAS G12D or G12R–mutated cancer and eliminate the tumor cells. Because the ELI-002 vaccine is an off-the-shelf agent, it does not have to be specially formulated to each individual.
“Patients who have undergone surgery for pancreatic cancer are still at risk for relapse…, even after they finish chemotherapy. This is especially true for patients who are positive for circulating tumor DNA [ctDNA], which puts them at a higher risk for relapse,” explained lead study author Shubham Pant, MD, Associate Professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. “When these patients do relapse, the disease is not curable, so this is certainly an area of unmet need,” he stressed.
Study Methods and Results
In the phase I AMPLIFY-201 trial, researchers assigned 25 patients with pancreatic and colorectal cancers who were at high risk of relapse and previously underwent curative-intent surgery to receive a maximum of 10 doses of the ELI-002 vaccine.
The researchers found that 84% of all patients and 100% of the patients in the two highest dose arms—including those who received the recommended phase II dose of 10 mg—demonstrated T-cell responses. The responses were predictive of reductions in tumor biomarkers and ctDNA clearance and correlated with an 86% reduction in the risk of relapse or mortality. For the patients who were above the median T-cell response level, the median recurrence-free survival was not yet reached compared with 4.01 months in those with a T-cell response level below the median.
According to the investigators, none of the patients experienced dose-limiting toxicities, cytokine-release syndrome, or any treatment-emergent adverse events above grade 3. The most common adverse events were fatigue (24%), injection-site reactions (16%), and myalgia (12%).
Conclusions
“It’s early, but we saw some promising results that this vaccine may help many of these patients avoid relapse, which could increase survival,” Dr. Pant underscored. “It also showed a favorable safety profile, which is exciting,” he concluded.
The researchers highlighted that the positive findings have led to a new phase II trial that will begin later in 2024 involving a new formulation of the ELI-002 vaccine targeting additional KRAS mutations.
Disclosure: This research in this trial was supported by Elicio Therapeutics. For full disclosures of the study authors, visit nature.com.
