Vaccine Candidate Delays Relapse of KRAS-Mutated Cancers

HOUSTON, TX ― A vaccine showed potential to prevent relapse of KRAS-mutated pancreatic and colorectal cancers for patients who had previously undergone surgery, according to a Phase 1 trial led by researchers at the University of Texas MD Anderson Cancer Center. Results were published recently in Nature Medicine. 

In the trial, patients with pancreatic and colorectal cancer who were considered at high risk of relapse received a maximum of 10 doses of the ELI-002 2P vaccine targeted toward KRAS G12D and G12R mutations. T-cell responses were seen in 84 percent of all patients and in 100 percent of those in the two highest dose cohorts, including those who received the recommended Phase 2 dose of 10 mg.  

T-cell responses were predictive of reduction in tumor biomarkers and circulating tumor DNA (ctDNA) clearance, and they correlated with an 86 percent 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. 

“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 (ctDNA), which puts them at a higher risk for relapse,” said principal investigator Shubham Pant, MD, associate professor of gastrointestinal medical oncology. “When these patients do relapse, the disease is not curable, so this is certainly an area of unmet need.”  

Training T cells to identify KRAS mutations

The multicenter AMPLIFY-201 trial is evaluating ELI-002 2P, a lymph node-targeted cancer vaccine designed to lower the likelihood of these relapses by “training” T cells to recognize KRAS mutations, allowing them to identify and eliminate KRAS-mutant cells. ELI-002 2P is also an off-the-shelf vaccine, meaning it does not have to be specially formulated for each individual. 

KRAS-mutated cancers make up about a quarter of all solid tumors, including 90 percent of pancreatic cancer patients, who most commonly have the G12D mutation.  

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

Some 25 patients participated in the trial, with a median age of 61. Of these, 84 percent were White, 8 percent were Asian and two patients were of an unreported ethnicity. Patients were 60 percent female. All 25 previously had surgery or another procedure designed to be curative, and seven previously had received radiation therapy.  

“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.”  

- This press release was originally published on the University of Texas MD Anderson Cancer Center website