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 

The phase 1a AMPLIFY-7P trial (NCT05726864) investigated the safety, immunogenicity, and preliminary antitumor activity of the adjuvant 

-mutant–specific lymph node-targeted amphiphile ELI-002 7P vaccine in this patient population. Results from the 

 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 

-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.

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Craig E. Devoe, MD, MS, discusses next steps for assessing the ELI-002 7P vaccine in patients with MRD–positive, KRAS-mutant PDAC and CRC.
 

Craig E. Devoe, MD, MS, discusses data for ELI-002 7P in patients with MRD-positive pancreatic and colorectal cancers after locoregional therapy

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 findings from the phase 1a AMPLIFY-7P trial (NCT05726864), a multicenter study evaluating the safety, immunogenicity, and preliminary antitumor activity of ELI-002 7P in patients with pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) harboring 

 mutations who are minimal residual disease (MRD) positive after standard locoregional treatments.

ELI-002 7P is an expanded spectrum vaccine that includes lymph node–targeted, amphiphile-modified 

 G12D/V/R/C/S/A– and G13D–mutant peptides with an amphiphile-modified CpG oligonucleotide adjuvant intended to expand polyfunctional mutant KRAS-specific T cells.

AMPLIFY-7P enrolled patients with PDAC or CRC who underwent prior locoregional therapy that included surgery and chemotherapy, with or without radiation. They needed to harbor a 

 G12D/R/V/C/S/A or G13D mutation; have no evidence of disease on imaging; and have MRD as detected via circulating tumor DNA (ctDNA) and/or serum tumor biomarkers.

The treatment protocol involved administering a fixed dose of Amph-CpG-7909 combined with two different doses of ELI-002 7P (1.4 mg and 4.9 mg), administered subcutaneously. Patients received 4 weekly doses, followed by 2 doses every 2 weeks, for a total of 6 doses, followed by a 2-week observation period before 4 additional booster doses were administered, Devoe says, The primary objective was to establish the safety profile of this regimen, assess immunogenicity by measuring T-cell responses, and evaluate preliminary antitumor effects.

Findings presented at the 2024 ASCO Annual Meeting showed that no dose-limiting toxicities occurred in patients treated at either dose level (n = 14). Devoe notes that local injection site reactions were observed; however, these were transient and decreased in intensity over time. Any-grade treatment-emergent adverse effects included fatigue (42.9%), malaise (21.4%), diarrhea (21.4%), abdominal distension (14.3%), and abdominal pain (14.3%). Notably, no instances of cytokine release syndrome or T cell–related toxicities were reported.

From an immunogenicity standpoint, the T-cell response rate was 100%, and the median fold change was 23.6. Further, both CD8-positive T-cell and CD4-positive T-cell responses were observed in 63.6% and 45.5% of patients, respectively.

Craig E. Devoe, MD, MS, discusses data for ELI-002 7P in patients with MRD-positive pancreatic and colorectal cancers after locoregional therapy.

Craig E. Devoe, MD, MS

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

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