What an mRNA melanoma vaccine may mean for cancer treatment

Introduction to the mRNA melanoma vaccine

0:00Hey, it's Ira, and you're listening to Science Friday. A new mRNA vaccine for melanoma is making headlines. Moderna and Merck recently announced results from their clinical trial, which suggests that this new vaccine in combination with another drug significantly reduced recurrence rates of the skin cancer in patients. The companies have not yet released full data from the trial. So how does the vaccine work, and does this mark the beginning of a new era of cancer treatments using mRNA vaccine

0:34technology? Here to explain is a physician whose patients were part of the drug trial, Dr. Michael Postow, Chief of the Melanoma Service at Memorial Sloan Kettering Cancer Center here in New York. Welcome to Science Friday. Thank you very much for having me. It's a pleasure. You're welcome. All right, Dr. Postow, can you put this news in context for us? Just how big a deal is this new vaccine? We in the melanoma field and at MSK are extremely excited about these new results. I think the most

1:04important aspect of a trial like this is the scientific principle that's established, in that this is the first time a cancer vaccine has been made on a personalized basis, meaning each individual patient has their own tumor, serve as the source of the vaccine creation. So this is the ultimate personalized medicine for each of his patients. And the fact that the top line results from the phase three study showed that this actually worked in combination with protruded to decrease the risk of melanoma recurrence is quite phenomenal. Okay, let's talk a bit more about the science.

The science behind personalized cancer treatments

1:41Take us into the weeds how this is personalized vaccine and how it's made. Each of our tumors is very unique. And the goal of a treatment like this in broad brushstrokes is to boost our own body's immune response against the specific aspects of the tumor that are unique to an individual, such that our own immune systems can seek and destroy anything that looks like that tumor in our bodies. And so what happens is that the tumor is removed from a patient, the DNA is sequenced, and there's a complicated computer algorithm, essentially, that determines

2:16what among the mutations that are present in the tumor are immunologically relevant, in that not all the mutations in the tumor are relevant for an immune response. But by seeing what genes are mutated in the tumor and what genes might be relevant to a productive immune response, an mRNA construct is made for that individual patient based upon characteristics of that individual patient's tumor. And then the patients receive this therapeutic vaccination. And the theory is that this boost that patient's immune response only against the aspects of the tumor that are within that patient's individual

2:51tumor. And by having that enhanced immunity, that has been shown to protect that patient from future melanomas coming back. So to use this vaccine, it's a personalized therapy. Each individual would have to be looked at individually, not just in mass as a vaccine. That's correct. Each patient has to have their own vaccine made for them. One vaccine wouldn't work for another patient because each patient's melanoma tumor is different. So there is a personalization to this that's really special in a trial like this. It does make it difficult as well, because it takes some

3:25time to manufacture a vaccine like this. And each of these treatments is a bespoke treatment for an individual patient. Many times when people think about vaccines, they think about treatments that are intended to prevent a disease from ever happening in the first place. And we think about this vaccination, or polio vaccination, and that type of a way. This personalized therapeutic cancer vaccination is not a prevention for melanoma in the first place. So it sounds like it's an expensive and time consuming process. We don't yet know what the

3:57price tag is, right? Is it the cost of a new treatment something you consider when treating patients? Absolutely. Cost is always important when we think about our treatments. We don't yet know what the cost of something like this could be. But recurrent melanoma in and of itself can be quite costly. Patients and families lose time away from work. More treatments that are often expensive or needed in the setting of recurrent melanoma. So when we ultimately see what the cost of an approach like this would be, it would be important to think about how many patients are able to have their

4:28melanomas prevented from recurring with this type of approach, and what could be the downstream cost savings with that type of therapeutic vaccine issue.

Applying the vaccine to other types of cancer

4:37Could this approach be used to treat other cancers too? We think that ultimately this could have implications for other cancers too. We haven't yet demonstrated the efficacy in other cancers to the extent that we have in melanoma at this juncture, meaning that in melanoma we finished a phase 3 study that showed the benefit here. However, there's really nothing specific about melanoma that this would only be expected to work in melanoma. And in many clinical trials that our institution, the Moe S. Loan-Kettering Cancer Center and otherwise, are testing this type of a

5:09vaccination approach in patients with other cancers like lung cancer, bladder cancer, kidney cancer. And I know now that this results with positive melanoma, likely more cancers do become. Well, that being the case, what is it about melanoma that made it a prime candidate to be the first type of cancer to try and treat with this new mRNA platform? I think there are two reasons why melanoma was the most exciting tumor type to start these types of studies. Number one, melanoma has long been believed to be one of the more immunogenic types of cancers.

5:42And then other immune therapy strategies related, but somewhat different than this vaccination approach, have demonstrated significant successes in melanoma. And therefore, a new immune therapy approach like this personalized cancer vaccine had a welcome home in the melanoma field to explore something like this. And melanoma, because it's induced by ultraviolet light in many situations, is associated with many different mutations. And so the success or anticipated success of vaccine creation, production, and execution is high in the melanoma field because there are a lot of

6:16mutations in melanoma. And so when we think about other cancers where this may be relevant, the number of mutations that could be relevant for success of the vaccine creation.

Combining the vaccine with existing immunotherapy drugs

6:25As we've talked about, patients in the trial were on the drug Keytruda in addition to this new mRNA vaccine. Are the vaccines intended as a complementary treatment to existing ones, or could a vaccine therapy replace other types of drugs entirely? In melanoma, this vaccine was tested with Keytruda because Keytruda is a current standard of care for this patient population that has had melanoma surgically removed and is at risk of recurrence. So the trial that we've conducted so far is testing

6:57the vaccine plus Keytruda versus Keytruda alone as the current standard by itself. Keytruda plus the vaccine, it makes sense as a combination because Keytruda is an immune enhancer as well. And so the idea is Keytruda globally enhances an immune response. And then the vaccine drives that immune response to the specific neoantigens and parts of the tumor that are relevant for that one individual patient. So it's a very welcome combination that makes scientific sense to combine them. In the future, one could think

7:29about different trials where Keytruda plus this therapeutic vaccination could be tested against other standard treatments to see how much better, or if it's better to use a psych of the vaccine with Keytruda against other standard treatments, potentially even including chemotherapy in certain malignancies. You said that not all the data has been released yet. What will you be looking for once that final data comes out? What we know so far is there's a statistically significant improvement in what's called recurrence-free survival, meaning how many patients will never have their melanoma ever come

8:03back whatsoever. And we know there's a significant improvement on a statistical level in what's called distant metastasis-free survival, meaning how many patients have their melanoma spread to a distant part in their body, like inside lungs, liver, bone, brain, for example. What we don't know yet is the degree of improvement. But the main question that we all are waiting on is, how much was the reduction in risk of recurrence? And what type of patient characteristics were associated with the greatest benefit in this

8:36type of an approach in this trial? And we are hoping in the coming months to have more information on that

Side effects and future clinical availability

8:41topic. Whenever we talk about a drug, we talk about possible side effects or drawbacks to this approach. Are there any here? Remarkably, this therapeutic vaccination approach is very well tolerated. It does not increase the rate of immune therapy toxicities otherwise that one might see would be true to by itself. Most of this knowledge is based on the earlier phases of this type of an approach. We're still waiting on the phase three results. But in general, with the earlier experience with this and recruiting patients myself in this particular trial, anytime you inject somebody with

9:15a shot, there is some redness or soreness, whether that scene has been injected, that's one side effect. But most patients tolerated that pretty well. And then the other side effect some people have was a little bit of fatigue and some chills or mild fever after the injection for a couple of days. Of course, when people hear about this story, when they listen to us talking about it, they're going to wonder how long it is before patients might be able to access this therapy. We still need to see the results of the phase three trial. And the FDA has not approved this

9:47at this juncture. So we are still in this time period where we need more information and we need to see how the regulatory agencies react to this type of an approach and ideally, hopefully approve it with their appropriate considerations in mind. So I would expect it would probably be at least several months, but it's hard for me to be more specific on when this might be available. I think at the moment that the, for patients to keep in mind is, this may be something to talk to your doctor and see if the clinical trial might be appropriate for you. But at the moment, this is not something that

10:18can be routinely administered.

10:21Now, I know you see what melanoma patients go through in your practice. I mean, this must really be an uplift of potentially having a new therapy to offer them. For sure. I think this is very exciting because when patients get diagnosed with melanoma and they have it surgically removed, I think the main issue, it's a very scary time for patients. And one thinks about the future and no one ever wants to deal with the recurrence of melanoma inside the body because that can be a life-threatening situation in certain situations. So the idea that

10:51you can take a treatment to help reduce the risk that melanoma will ever be a problem again is a remarkable advance. And I think one that we can celebrate and we can tell our patients more competently that the odds of surgery and treatment being curative for them in the long long have now been shown to be increased. And we're delighted with that information. Dr. Postow, thank you for taking time to be with us today. Very interesting stuff. Thank you very much for having me. It's a pleasure. Dr. Michael Postow, Chief of the Melanoma Service at Memorial Sloan Kettering Cancer Center in New York.

11:23This episode was produced by Shoshana Buxbaum. Did you enjoy this conversation? Do you want to give us some feedback or suggest a topic we should cover? Give us a call 877-4-SCI-FRI. That's 877-4-SCI-FRI. Our listener line is always open. I'm Ira Plato. We'll catch you next time.

11:53Thank you. Thank you. Thank you.