Off-The-Shelf Vaccine Elicits Durable Responses in Pancreatic, Colorectal Cancers

Dr. Zev Wainberg of UCLA recently spoke with CURE about trial results concerning the cancer vaccine ELI-002 2P.

A cancer vaccine is eliciting durable responses and is associated with reduced relapse risk among patients with pancreatic and colorectal cancers, as an expert explained in an interview with CURE.

“What we're showing here is that a group of patients who had a profound immune response after administration of this vaccine, and had a much lower risk of cancer coming back or dying from their pancreatic cancer and colon cancer than we would have anticipated based on historical references,” said Dr. Zev Wainberg. Wainberg is a professor of medicine at the David Geffen School of Medicine at UCLA and a researcher in the UCLA Health Jonsson Comprehensive Cancer Center.

Wainberg is the first author of a study published in Nature Medicine on ELI-002 2P, a vaccine designed to stimulate the immune system in order to target the common cancer-driving KRAS mutation, as explained in a news release from UCLA.

Learn More: Why Cancer Vaccines ‘Are A Marvel’

After a follow-up of 19.7 months, the median relapse-free survival was 16.33 months and median overall survival was 28.94 months in the study, which included follow-up data from the AMPLIFY 201 phase 1 clinical trial of 25 patients evaluating the safety and effectiveness of the lymph node-directed vaccine.

Participants in the study, 20 of whom had pancreatic ductal adenocarcinoma and five of whom had colorectal cancer, had undergone surgery and displayed signs of minimal residual disease before receiving a series of injections with ELI-002 2P.

Looking ahead, UCLA has announced that the research team has completed enrollment in a larger phase 2 study of ELI-002 7P, a next-generation iteration of the vaccine.

CURE: For patients, what should be the big takeaway from this news?

Wainberg: What we're showing here is that a group of patients who had a profound immune response after administration of this vaccine, and had a much lower risk of cancer coming back or dying from their pancreatic cancer and colon cancer than we would have anticipated based on historical references.

So that, with the 20-month follow-up time we had in the study, that's what we saw, that the most likely scenario is that the majority of them would have reccurred earlier, and yet the people who had the highest immune response, which was about two-thirds of people on the study, the majority of them had not recurred, and none of them had died from their cancer.

We have to do the ultimate, which is the randomized study, which has actually already been completed. This was the phase 1 long follow-up study, and we've already done a randomized phase 2 study comparing the vaccine to no vaccine in the same group of patients, in essence. And so that study, we should have the results in 2026.

This is an off-the-shelf vaccine. What does that mean?

It means it's a vaccine that can be readily and easily available, because it doesn't have to be personalized. And personalized means that you have to send the tumor in and do a lot of manipulation to create the vaccine. Because the target of interest in this vaccine was a KRAS, which is so ubiquitous amongst 90% of pancreas cancer, for example, and 50% of colon cancer, because of the high frequency of that, it's a good candidate for an off-the-shelf vaccine

How does this vaccine work?

This vaccine works like most vaccines hopefully work, which is to engage and stimulate an immune response against a cancer protein, and that includes T cells and B cells and all your immune cells to recognize cancer cells as foreign and to engage in the fight against them.

Did anything in these findings particularly surprise you and your colleagues?

I think we were pleased in a surprising way, that two-thirds of patients mounted a strong enough immune response. So to be fair, I don't think we knew that that would be the result. I think there was hope that it would be that high. It's higher than we might have expected. We've had a lot of struggles in immunotherapy, in general, in pancreatic cancer. The classical immunotherapy approaches that your audience is, of course, more familiar with, the checkpoint inhibitors, they don't seem to work in pancreatic cancer in almost anybody. To be fair, they haven't been studied in the exact same context the majority of the time, but in large part, has not been a success the way it has been in lung, bladder, kidney [cancer], all these diseases where we use those drugs. So to have it work, and to have it engaged in immune response to a KRAS-producing vaccine, to me, at a high enough frequency, was quite surprising, in a good way,

If this vaccine does make it to market,what unmet needs would this address?

One of the challenges that's quite unique in pancreatic cancer is that even after the patient gets an operation and gets chemo and radiation, whatever else they're going to do, they still have a very, very high risk of recurrence, and that is quite unique, I would say. It's the highest risk of recurrence after a cancer has been removed compared to any others — breast, colon, lung, you name it. Because of that high risk, they're always, unfortunately, going to have to deal with it again, and sometimes in a fatal way. So it would fit a huge unmet need, if the randomized trials are supportive of that, and we get it to registration.

Is this a design that could be applicable to other solid tumors if you find great success here?

This vaccine is quite specific, insofar as it's targeting tumors patients that have this KRAS mutation. So, it is off the shelf, but it's in people who have that mutation, which is so high in pancreas cancer and colon cancer, and it could be applicable, in my view, if we study it properly, in all of those cancers where they have a KRAS mutation.

Reference

1. “Off-the-shelf cancer vaccine elicits strong immune response in patients with pancreatic and colorectal cancer,” UCLA, https://www.uclahealth.org/news/release/shelf-cancer-vaccine-elicits-strong-immune-response-patients
2. “Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: phase 1 AMPLIFY-201 trial final results” by Dr. Zev Wainberg et al., Nature Medicine.

Transcript has been edited for clarity and conciseness.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.