Cancer Vaccine Likely ‘Several Years’ Away From Wide Availability

A vaccine for the postsurgical treatment of KRAS-mutated pancreatic and colorectal cancers, ELI-002, is showing promising early study results — but any potential broad commercial availability of the drug is likely several years away, as one researcher tells CURE®.

“We’re certainly trying to advance as quickly as possible,” said Dr. Christopher Haqq, chief medical officer and vice president, head of research and development for biotechnology company Elicio Therapeutics, Inc., in an interview with CURE®.

Haqq was among the investigators of a recent phase 1 clinical trial studying ELI-002, the results of which were published in the journal Nature Medicine and showed that mKRAS-specific T cell responses and tumor biomarker responses were observed in 84% (21 of 25) of patients, while biomarker clearance was observed in 24% (six of 25) of patients, and the median relapse-free survival (how long a patient lives without signs or symptoms of disease) was 16.33 months, with no dose-limiting toxicities observed.

ELI-002, as explained in a press release issued by The University of Texas MD Anderson Cancer Center, is a lymph node-targeted vaccine intended to decrease the chance of postsurgical relapse by enabling a patient’s T cells, part of the immune system, to identify and destroy cells with KRAS G12D and G12R mutations.

“What we've seen in our past immune therapies for cancer is that the immune system has the best chance to eradicate all the remaining cells when it's given a good ratio between the T cells and the tumor cells,” Haqq said. “So, in this way of treatment, where we go after surgery, (which is) when the disease is confined to microscopic nests of cells, that's the time when the T cells are able to maximize their effort against the tumor. And we reasoned that that would be a really good way to evaluate the drug in the first trial. So, we were really happy to make that selection for patients.

“But, it's quite possible that we could go in both directions for the future, because we've seen quite a bit of anti-tumor effect in our first trial so it would be reasonable to evaluate this candidate in more advanced cancer. … In the future, and we don't have a current plan for this, it's very possible we could go into the preventative mode, and actually vaccinate people who don't yet have cancer to prevent the outgrowth in the future of this type of cancer mutation, KRAS, because these are the driver mutations that actually cause the cancer to form.”

Approximately 25% of solid tumors, including 90% of pancreatic cancers, are KRAS-mutated — and ELI-002 has been designed as an “off-the-shelf” vaccine that does not have to custom-made for a specific patient, MD Anderson Cancer Center explained in the news release.

“That's a very important advantage in especially the cancer types we're studying, like pancreatic cancer,” Haqq said. “There, you really want to have off-the-shelf availability so that immediate deployment of the vaccine is possible because with many mRNA vaccines, for example (by contrast), there's up to a nine-week lead time before that can be available. And in that time, a patient might have their tumor progress. So, we want to treat as early as we can so that the T cells can go after the residual nests of microscopic tumor cells and deal with them before they've had time to grow into something larger.”

This same approach, Haqq posited, could also eventually be used to treat different mutations and cancer types.

“The presence of one of these KRAS mutations is what we call a neoantigen, meaning a change that's present in a tumor but not in other normal tissues of the body,” Haqq explained. “And so, it's a very good situation for safety, because we know if we make a strong immune attack on that variant, it's not likely that we would have any effect on the rest of the normal tissues in a patient's body. So, this is a general finding. The fact that we can do this for KRAS means that we could do it for other mutations that are present in other cancers. Numerous of those are out there waiting for better therapies, including BRAF and P53.”

The first patient was recently dosed with a new formulation of ELI-002 designed to target more KRAS mutations in a phase 2 clinical trial, with the approximately 135 patients randomized two-to-one for 90 patients to initially receive treatment from ELI-002, and members of the observation group having the ability to elect to crossover to receive ELI-002 if their cancer progresses.

“Most patients with pancreatic cancer would have (a KRAS mutation), and that's the tumor type under study in this,” Haqq said. “And the other thing is to focus it on the situation where the patients have had surgery and chemo, but the disease has not returned on an imaging scan yet. So, that's the other major (participation) criteria. I think, right now, there's no other standard treatment that's given to patients in that window of time.

“So (this trial) is a great opportunity to contribute to science, because normally, the patients would just be getting periodic imaging scans to see if their cancer has returned. And this would give them a way to participate in a study that would see if ELI-002 can reduce the relapses that occur and perhaps prolong survival as well.”

Transcript:

We'll be talking to the regulators like the US Food and Drug Administration and others around the world to align on the data that we'll need to provide for a marketing application. And so, we haven't had that input yet. So I can't give an exact answer for you (on when the vaccine will be commercially available). But we'll work as fast as possible. It's even possible that the type of evidence that we gather in this randomized study could serve that purpose. But we won't know until we have further discussion.

I think because there's so much need for better therapy, in especially this particular situation where today patients are just waiting and waiting for scans to show that they have their cancer return. And in pancreatic cancer, it returns in over 80%, it's a very likely scenario that a relapse will occur. I think that's the perfect scenario where we could work with the stakeholders, the regulators and others to move as quickly as possible. So we're certainly trying to advance as quickly as possible, but it'll be several years most likely before this drug is broadly available.

Transcript has been edited for clarity and conciseness.

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