New vaccine may help stop return of certain colorectal, pancreatic cancers

• Researchers report that a new vaccine could one day help prevent the recurrence of colorectal and pancreatic cancer in some individuals.
• The vaccine is still in early development, but the researchers said it appeared safe and effective in a small study.
• Colorectal and pancreatic cancer are two of the most deadly and difficult to treat forms of cancer.

Researchers are reporting that a new vaccine could help prevent the reemergence of colorectal and pancreatic cancer in high-risk people who have previously undergone cancer treatment.

The findings, published in the journal Nature Medicine, are based on the AMPLIFY-201 trial, a phase 1 trial for the drug ELI-002, conducted by researchers at The University of Texas MD Anderson Cancer Center.

Elicio Therapeutics, the makers of ELI-002, funded the study.

Although the drug is still early in development, researchers in charge of the trial say the results are promising.

Colorectal and pancreatic cancer are two of the most deadly forms of cancer. They are the second and third, respectively, leading cause of cancer deaths in the United States, behind only lung cancer. Combined, the two were responsible for more than 100,000 deaths in the United States in 2023.

The new vaccine works by targeting two genetic mutations of KRAS genes, specifically KRAS G12D and KRAS G12R.

KRAS genes help to regulate cell division and growth. They aren’t inherently harmful, but when they are mutated can become cancerous.

KRAS mutations are found in up to one-in-four cases of all forms of cancer, but in colon cancer that number jumps to more than one-in-three.

Additionally, KRAS mutations are also associated with lower rates of survival and more aggressive tumor growth.

 

An “off the shelf” cancer vaccine

The goal of the new vaccine is to prevent the cancer from returning after it has been successfully cleared through traditional treatment. It does this by teaching the immune system to target KRAS mutations.

The vaccine is also an “off the shelf” vaccine, meaning that it doesn’t need to be tailored to an individual person and can easily be added as an adjuvant cancer therapy.

“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,” Dr. Shubham Pant, a professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center and lead investigator of the clinical trial, told Medical News Today.

“This is an exciting new type of immunotherapy that is specifically designed against mutant proteins in the cancer cells,” Dr. Christina Annunziata, a senior vice president in extramural discovery science at the American Cancer Society who was not involved in the research, told Medical News Today.

 

Immune system response is important

Pant and his team observed a T cell response, an indicator that the vaccine has successfully activated the immune system, in more than four-in-five of the participants in the trial.

All of the participants who received the highest dose of the drug produced a T cell response. A stronger T cell response was associated with greater chances of survival and lower recurrence of cancer.

However, participants needed to hit a certain threshold for their T cell response to see benefits. Participants who had a T cell response higher than the median did not have a recurrence of cancer, although follow-up is ongoing. Meanwhile, those who did not meet this threshold had an average recurrence of cancer 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, which is not a word you get to say very often in oncology research,” Dr. Christopher Chen, an assistant professor of oncology and the director of the Early Drug Development Program at Stanford University in California who wasn’t involved in the study, told Medical News Today.

Researchers also monitored circulating tumor DNA (CTDNA) levels in the bloodstream, a biomarker of tumors and cancerous cells. High levels of CTDNA can indicate the presence of cancer, whereas decreasing quantities can indicate a shrinking tumor. If no CTDNA is present in the bloodstream it can signal that the person is in remission and there is no sign of cancer.

Researchers said they observed reduction in CTDNA levels In 84% of the trial participants.

The results of the trial have now led to a subsequent 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.

 

Trial met safety and tolerability goals

For the trial, researchers recruited 25 people who had already successfully undergone surgery and chemotherapy for cancer but were considered high risk for the cancer recurring.

Twenty of the participants were previously treated for pancreatic cancer while five had colorectal cancer. The trial took place between 2021 and 2023.

The average age of participants in the trial was 61. The majority were white (84%) while 8% were Asian. Sixty percent of patients were female.

Participants received a fixed dose of Amph-Peptides 2P (G12D and G12R, 0.7 milligrams each) while the amount of another compound called Amph-CpG-7909, which enhances the effectiveness of the treatment, was gradually increased from 0.1 milligram to reach 10 milligrams over the course of the trial.

The researchers administered a series of six injections during the initial phase of the trial, followed by four booster shots later on.

Researchers wanted to establish the safety and tolerability of the drug before moving to a larger pool of participants. The study indicates they have met those goals.

None of the participants experienced toxicity related to dose, meaning that the drug was safe at every level it was administered. Additionally, no serious adverse health outcomes or side effects were reported, such as cytokine release syndrome, which can develop from the use of immunotherapies.

The most common side effects of the drug were fatigue, injection site reaction, and myalgia (muscle aches).

“The side effects in the study for the vaccine appeared to be quite modest, especially compared to something like chemo,” said Chen.

https://www.medicalnewstoday.com/articles/new-vaccine-may-help-stop-return-of-certain-colorectal-pancreatic-cancers#Trial-met-safety-and-tolerability-goals