Moving a KRAS Vaccine Into the Preoperative Setting: Phase 1 Pancreatic Cancer Trial Adds Chemotherapy and a PD-1 Inhibitor

The challenge of pancreatic cancer lies not only in whether the tumor can be removed, but also in how to enable the immune system to recognize its most fundamental driver mutation before the disease spreads. A newly launched Phase 1 trial is moving a KRAS-targeted vaccine into the preoperative setting, seeking to integrate standard chemotherapy, mutant antigens, and immune checkpoint inhibition into a neoadjuvant treatment strategy.

This open-label, randomized pilot trial is registered as NCT07671339 and is expected to enroll 20 patients with KRAS-mutated, resectable or borderline resectable pancreatic ductal adenocarcinoma. All participants will receive mFOLFIRINOX chemotherapy and ELI-002 7P, with one group also receiving the PD-1 inhibitor tislelizumab. After completing preoperative treatment, participants will undergo tumor resection as planned by the research team.

ELI-002 7P is an experimental immunotherapy targeting seven common KRAS mutations: G12D, G12V, G12R, G12C, G12A, G12S, and G13D. It is designed to direct mutant KRAS antigens to the lymph nodes, training T cells to recognize cancer cells carrying these mutations; tislelizumab, meanwhile, relieves the suppression of immune responses mediated by PD-1 signaling. Whether the two can complement each other within the highly immunosuppressive tumor microenvironment of pancreatic cancer is the central biological question the trial seeks to answer.

But this is not yet a trial designed to demonstrate efficacy. The primary endpoint is the proportion of patients who experience grade 3 or higher treatment-related adverse events within two years; surgical timing, KRAS-specific T-cell responses, and disease-free survival are secondary assessments. The team will also analyze blood, preoperative tumor biopsies, and resection specimens to track circulating tumor DNA, tumor markers such as CA19-9, immune-cell infiltration, and changes in the tumor microenvironment.

### Background

KRAS has long been regarded as pancreatic cancer’s most critical driver, yet one that is difficult to target directly. In recent years, small-molecule inhibitors targeting specific KRAS subtypes have gradually moved into earlier lines of treatment; ELI-002 7P takes a different approach, enabling the immune system to recognize multiple mutations rather than directly blocking the KRAS protein. The sponsors said an earlier version of the therapy induced immune responses in a Phase 1 study of postoperative patients; the new trial moves the intervention to before surgery, allowing researchers to directly compare tumor tissue before and after treatment.

The trial is led by Memorial Sloan Kettering Cancer Center, and registry data indicate that enrollment has begun; centers including Dana-Farber, Johns Hopkins, and MD Anderson are expected to join gradually. Because the study includes only 20 patients and is not primarily designed to test improvements in survival, even if T-cell activation, declines in tumor markers, or pathological responses are observed, they can only serve as a basis for subsequent larger studies. At this stage, the most important questions remain whether the three treatments can be tolerated when used together and whether immune changes can translate into a lower risk of recurrence.