Dr Devoe on Next Steps for Evaluating ELI-002 7P in MRD+ KRAS-Mutant PDAC and CRC

Craig E. Devoe, MD, MS, chief, Division of Medical Oncology and Hematology, R. J. Zuckerberg Cancer Center, chief, Hematology-Oncology Service, Long Island Jewish Medical Center and North Shore University Hospital, discusses next steps for validating the safety and activity of the ELI-002 7P vaccine in patients with minimal residual disease (MRD)–positive pancreatic ductal adenocarcinoma (PDAC) or colorectal cancer (CRC) harboring KRAS mutations.

The phase 1a AMPLIFY-7P trial (NCT05726864) investigated the safety, immunogenicity, and preliminary antitumor activity of the adjuvant KRAS-mutant–specific lymph node-targeted amphiphile ELI-002 7P vaccine in this patient population. Results from the 2024 ASCO Annual Meeting did not show any dose-limiting toxicities across either dose levels studied (n = 14), Devoe reports. There were also no significant systemic adverse effects and only local injection site reactions were observed. Moreover, the T cell response rate was 100%, with a median fold change of 23.6. Robust immune responses were observed, with CD8- and CD4-positive T-cell responses in 63.6% of and 45.5% of patients, respectively.

One particularly exciting aspect of these findings was the observation of antigen spreading, Devoe reports. The vaccine targets the KRAS-mutated protein, but T-cell responses were also observed against passenger mutations identified through exome sequencing of the tumors, he notes. This suggests that the vaccine not only induces an immune response against the primary KRAS mutation but also broadens the immune attack to include other mutations, effectively creating a more personalized and diversified T-cell response against the cancer, he explains. This broadened response could enhance the effectiveness of the vaccine, Devoe says. Notably, the vaccine was well tolerated, with only local injection site reactions observed and no significant systemic adverse effects, Devoe adds.

The phenomenon of antigen spreading requires further investigation, he continues. Current results are based on small patient cohorts and only 2 different dose levels of the vaccine. As the evaluation of this vaccine progresses, researchers aim to assess more definitive clinical outcomes, Devoe states. Preliminary biomarker data have shown that the vaccine can reduce levels of circulating tumor DNA and cancer antigens such as CEA and CA19-9, he notes.

The randomized phase 2 portion of the study is now open in patients with pancreas cancer, Devoe says, adding that this phase will evaluate clinical end points such as relapse-free survival. Additionally, the study includes a crossover component to evaluate if patients who relapse in the observation arm could benefit from receiving the vaccine at that point, he adds. This could provide further insights into the vaccine’s ability to induce both immunological and clinical responses, even after disease progression, Devoe concludes.