A statement from the University of Texas MD Anderson Cancer Centre in January 2024 reported on the “potential” of a vaccine candidate in a Phase I trial, the results of which were published in Nature Medicine. The vaccine showed promise in the prevention of relapse of KRAS-mutated pancreatic and colorectal cancers for patients who had previously undergone surgery. 25 patients considered at high risk of relapse were given a maximum of 10 doses of ELI-002, which “enhances lymph node delivery and immune response” through amphiphile (Amph) modification of G12D and G12R mutant KRAS (mKRAS) peptides and CpG oligonucleotide adjuvant.
CRC and PDAC and treatment opportunities
Colorectal cancer (CRC) and pancreatic ductal addenocarcinoma (PDAC) are reportedly the second and third leading causes of cancer death, with “standard locoregional treatment for resectable disease” offering less than 20% 5-year survival and “few effective treatments for relapse”. Widely expressed KRAS driver mutations (mKRASs) present “attractive immunotherapy targets” for tumour survival with “uniform expression” throughout disease progression. However, mKRAS-directed T cell therapy is restricted to “select mutations” and HLA alleles, demands “complicated logistics”, is costly to manufacture, and brings “potential cytokine release syndrome and neurotoxicity”.
“In contrast, vaccination offers potential to expand endogenous mKRAS-directed T cells across diverse HLA backgrounds, with simplified manufacturing and off-the-shelf availability.”
ELI-002 in trial
ELI-002 is a three-component lymph-node-targeted vaccine that comprises Amph-modified G12D and G12R mKRAS long peptides as well as Amph-modified Toll-like receptor 9 (TLR9) agonistic CpG-7909 DNA.It lowers the likelihood of relapse by “training” T cells to “identify and eliminate” KRAS-mutant cells. Amph vaccine components are modified with diacyl lipids for “molecular hitchhiking” to enhance lymph node accumulation and efficient delivery APCs. It is an off-the-shelf vaccine.
The multicentre trial (AMPLIFY-201) enrolled 25 patients with a median age of 61. T cell responses were seen in 84% of all patients and in 100% of those in the two highest dose cohorts. A statistically significant improvement in median recurrence-free survival was noted for patients above the median T cell response level.
Dr Shubham Pant, associate professor and principal investigator, commented that “patients who have undergone surgery for pancreatic cancer are still at risk for relapse” even after chemotherapy has finished. Indeed, for patients who are “positive for circulating tumour DNA” there is a “higher risk”.
“When these patients do relapse, the disease is not curable, so this is certainly an area of unmet need.”
No dose-limiting toxicities, cytokine release syndrome, or treatment-emergent adverse events above Grade 3 were observed. Dr Pant described the “favourable safety profile” as “exciting”.
“It’s early, but we saw some promising results that this vaccine may help many of these patients avoid relapse, which could increase survival.”
The trial was sponsored by Elicio Therapeutics.
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