Elicio Therapeutics has announced positive phase 1 clinical data for its cancer vaccine ELI-002, showing promising results as a potential treatment for pancreatic and colorectal cancers. The AMPLIFY-201 trial, conducted at The University of Texas MD Anderson Cancer Center, demonstrated robust immune responses in patients with these aggressive cancer types.
Targeting KRAS Mutations
The ELI-002 vaccine works by targeting genetic mutations in KRAS genes, specifically KRAS G12D and KRAS G12R variants. KRAS genes normally help regulate cell division and growth, but when mutated can become cancerous. These mutations are found in up to one-in-four cases of all forms of cancer, with the number jumping to more than one-in-three in colon cancer cases.
The vaccine has the potential to target up to seven KRAS variants simultaneously, covering 88% of pancreatic ductal adenocarcinoma (PDAC) cases, which accounts for 90% of pancreatic cancers. KRAS mutations are also associated with lower survival rates and more aggressive tumor growth.
Clinical Trial Results
Results from the phase 1 trial showed that 84% of patients had an average 56-fold increase in the number of antitumor T cells. All participants who received the highest dose of the drug produced a T cell response, indicating successful immune system activation.
"What we are trying to do is we're trying to kill micrometastatic disease. That means a disease that you cannot see on scans, but still, you know that the disease is going to come back in four to six months because it's hanging around. We basically use this vaccine to kill that," said Dr. Shubham Pant, professor in the Department of Gastrointestinal Medical Oncology at MD Anderson and lead investigator of the clinical trial.
The study also monitored circulating tumor DNA (CTDNA) levels in the bloodstream as a biomarker of tumors and cancerous cells. Researchers observed a reduction in CTDNA levels in 84% of trial participants, with 24% achieving complete elimination of blood biomarkers of residual tumors.
Survival Benefits
Patients who demonstrated strong immune responses experienced significant clinical benefits. An 86% reduction in the risk of cancer progression or death was observed in patients with robust immune responses. Participants who achieved a T cell response higher than the median did not experience cancer recurrence during the follow-up period, while those below this threshold had an average recurrence within 4 months.
"What I think is most critical here is that in patients with pancreatic cancer and colorectal cancer, when it's been surgically removed, there's still often a high rate of relapse. And when it does relapse, unfortunately the cancer is often incurable. So this is really a critical window of care. If we can stave off relapse, delay, or prevent it altogether, we can cure more patients," said Dr. Christopher Chen, assistant professor of oncology and director of the Early Drug Development Program at Stanford University.
Development Background and Future Plans
The vaccine was originally developed by Professor Darrel Irvine at MIT and colleagues, then refined by researchers at Elicio, an MIT spinout. In preclinical mouse models of HIV, melanoma and cervical cancer, researchers found that peptides from the vaccine modified to bind albumin produced T cell responses five to ten times greater than peptides alone.
The vaccine is designed as an "off the shelf" treatment, meaning it doesn't need to be tailored to individual patients and can easily be added as an adjuvant cancer therapy. Elicio is currently testing the formulation targeting seven KRAS mutations and plans to address other KRAS-driven cancers, including non-small cell lung cancers.
The positive phase 1 results have led to advancement into a phase 2 trial that will further test the safety and efficacy of ELI-002. "This is early and promising and we're going to follow this up at a bigger trial to validate these findings, but it is exciting in a way that it gives us a first look that, potentially, some of these patients can be cured," said Pant.
