The promotion of immune response is gaining ground as an essential strategy for fighting pancreatic cancer. One study that has shown promise in this area, the phase 1 AMPLIFY-201 trial (NCT04853017), investigated the amphiphile vaccine ELI-002 2P designed to stimulate antigens particular to KRAS-mutated cancers.
Recent results from extended follow-up showed delayed recurrence in patients at high risk after locoregional treatment, and importantly they correlated to T cell response and showed indications of antigen spreading to cause a greater immune response beyond what the vaccine specifically targeted.
“What we’re seeing in across a bunch of studies—not just this one, across a few other mRNA vaccines and otherwise that are being done in pancreatic cancer—is that we are able to engage an immune response, and that does seem in these phase 1 studies to correlate with good outcomes,” Zev A. Wainberg, one of the investigators in the trial, said in an interview with Targeted Oncology.
Wainberg, who is a professor of medicine at UCLA and co-director of the UCLA Gastrointestinal Oncology Program, discussed the significance of the AMPLIFY-201 trial, next steps for this vaccine platform, and the signs of progress he has recently seen in this challenging disease setting.
Targeted Oncology: Could you discuss the background of the study and how the vaccine ELI-002 2P is being used?
Zev A. Wainberg, MD: The principle here is that you can engage the immune system in patients who have had surgery and chemotherapy and now are at very high risk of recurrence. We know that statistically in the case of pancreatic cancer and even in colorectal cancer, there is a fairly high tendency to recur despite all of those other treatments, so we investigated this vaccine, ELI-002 2P, in that group of patients after surgery and all treatment for their cancers. Patients received a series of vaccinations in this study, and this is the long-term follow-up reporting of that result.
What were the key outcomes with the updated follow-up?
With longer follow-up of is almost 20 months, which is a good time frame for pancreatic cancer, you see that in the group of patients who mounted a sufficiently good immune response, which we classified as about two-thirds of the patient population, 17 out of 25, those patients had a much lower risk of their cancer coming back or dying from their cancer when compared with historical controls, what we might have expected from the same patient population. We know that group of patients, particularly with pancreatic cancer, have upwards of a 80% chance of the cancer coming back within a year, and the fact that we had almost no patients dying in the follow-up of the study who got that high immune response and only 4 of them [whose disease] recurred amongst that group, gives us some excitement. That group of patients, particularly those who mounted a strong immune response, had some effective mechanism to delay or even prevent the cancer from coming back.
This was a long-term result of a phase 1 study, which, of course, has a lot of caveats, the biggest being there’s no control arm; there’s no randomization. We’ve already completed the randomized phase 2 study of this vaccine vs observation. It’s a next-generation version of the same vaccine, which covers a higher percentage of KRAS mutations. That study has now completed enrollment, and the results will be expected in 2026.
ELI-002 2P covered some KRAS isoforms, [G12D and G12R]. ELI-002 7P covers a much broader range of KRAS mutations, and KRAS is the target for this vaccine. It’s an off-the-shelf vaccine, but off-the-shelf in the sense that only patients with KRAS mutations were enrolled.
What is your takeaway from the best outcomes being associated with a significant T cell response?
There are a lot of things that we wonder about. No. 1, why doesn’t every patient mount a great T [cell] immune response? It’s been shown across studies that some people just don’t [have a response]. Secondarily, how to keep it engaged? One of the premises here is, you don’t want just a short-term response. You want a durable and sustained response. That’s the premise behind long follow-ups of these studies to see if that’s really the case. That is why you have to follow long-term results of these studies.
The second reason is that the so-called hypothesis of antigen spreading is an important one for immunologists, and seems to have been something that we were able to achieve here in that a number of the tumor-specific T cell responses were not exclusively KRAS dependent, such that the ability of the so-called bystander T cells that were to join in on the immune engagement was something that was demonstrated.
What are the next steps with this research?
The randomized phase 2 trial, which has completed enrollment, randomly assigned patients in a 2:1 ratio to either getting the 7P version vs observation. Now that result, which we are eagerly awaiting and expect in 2026 would, if compared with a control group we have a lower rate of recurrence or even lower rate of death, would really be meaningful in a very significant way in this field. Beyond that, we may ultimately have to do a phase 3 study, which would be placebo or sham placebo vaccine, theoretically to meet the muster for FDA registration. But a lot depends on the phase 2 study.
Are there any other settings with KRAS mutations where you might see the vaccine being used?
In colorectal cancer, even in those patients with RAS mutations, the risk of recurrence is lower after all treatment, but it still exists. We showed that in the 5 patients who were enrolled [with colorectal cancer]. I think in theory, it would be applicable to any patient with RAS mutations who are at high risk of recurrence. The risk is obviously different across cancers: pancreas the highest and colon [being] lower, but patients with lung cancer have RAS mutations and a bunch of other patients have RAS mutations. I think it could be applied more extensively.
What else is important to know about the developments in this field?
What we’re seeing in across a bunch of studies—not just this one, across a few other mRNA vaccines and otherwise that are being done in pancreatic cancer—is that we are able to engage an immune response, and that does seem in these phase 1 studies to correlate with good outcomes.1,2 None of these studies have been randomized; they’ve all been single arm. But now the randomized study for this vaccine, ELI-002 7P has been completed, and [for] the mRNA vaccine [NCT05968326] is ongoing. The efforts are already being done to see if this translates in a randomized context.
The big advantage we have now, perhaps more than before, is that we acknowledge which patient population is the best one to be studying this vaccine, which is this group of patients with no visible disease, but we know are very likely to recur and recognize them. We don’t want to do these vaccine studies in people with advanced disease; [that is] probably not the right approach in this area. It has real scientific promise.
What else are you seeing or working on that is exciting to you?
I think pancreatic cancer, not just this vaccine study but in general, is entering a whole new phase, and I have never been so optimistic about pancreatic cancer clinical trials as I am today. It’s not just this vaccine. It’s not just some of the second-generation immunotherapy drugs that we’re now seeing hope and optimism about, but it’s this entire field of KRAS-targeted therapies, which you’ll see lots of studies in the next year or 2 that are going to hopefully be transformational.
I [think that] moving off of some chemotherapy and moving more in the direction of targeted therapy for this disease, which we haven’t been able to do to a large extent, is where we’re headed. I am quite optimistic that some of these results will pan out for some of these agents in the randomized trials. That is, to me, the most exciting thing going on in pancreatic cancer.
References:
1. Wainberg ZA, Weekes CD, Furqan M, et al. Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: phase 1 AMPLIFY-201 trial final results. Nat Med. Published August 11, 2025. doi:10.1038/s41591-025-03876-4
2. Sethna Z, Guasp P, Reiche C, et al. RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer. Nature. 2025;639(8056):1042-1051. doi:10.1038/s41586-024-08508-4