What an mRNA melanoma vaccine may mean for cancer treatment

Moderna and Merck say an mRNA vaccine reduced melanoma recurrence in a clinical trial. Could this usher in a new era of cancer treatment?

• 0:02Speaker 00

  Hey, 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 technology? Here to explain is a physician whose patients were part of the drug trial, Dr. Michael Pastow, Chief of the Melanoma Service at Memorial Sloan-Kettering Cancer Center here in New York. Welcome to Science Friday.

• 0:47Speaker 01

  Thank you very much for having me. It's a pleasure.

• 0:50Speaker 00

  You're welcome. All right, Dr. Pastow, can you put this news in context for us? Just how big a deal is this new vaccine?

• 0:58Speaker 01

  We in the melanoma field and at MSK are extremely excited about these new results. I think the most important 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 3 study showed that this actually worked in combination with KEYTRUDA to decrease the risk of melanoma recurrence is quite phenomenal.

• 1:37Speaker 00

  Okay, let's talk a bit more about the science. Take us into the weeds, how this is personalized vaccine and how it's made.

• 1:45Speaker 01

  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 what 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.

• 2:26Speaker 01

  But by seeing what genes are mutated in the tumor and what genes might be relevant to a product of the immune response, an mRNA construct is made for that individual patient based upon characteristics of that individual patient's tumor. And then the patient receives this therapeutic vaccination, and the theory is that this boosts that patient's immune response only against the aspects of the tumor that are within that patient's individual tumor. And by having that enhanced immunity, that has been shown to protect that patient from future melanomas coming back.

• 2:58Speaker 00

  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?

• 3:08Speaker 01

  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 time 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 tetanus vaccination, polio vaccination, and that type of a way. This personalized therapeutic cancer vaccination is not a prevention from melanoma in the first place.

• 3:50Speaker 00

  So it sounds like it's an expensive and time-consuming process. We don't yet know what the price tag is, right? Is it the cost of a new treatment something you consider when treating patients?

• 4:03Speaker 01

  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 are 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 melanomas prevented from recurring with this type of an approach, and what could be the downstream cost savings with that type of therapeutic vaccination.

• 4:36Speaker 00

  Could this approach be used to treat other cancers, too?

• 4:40Speaker 01

  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, Memorial Sloan-Kettering Cancer Center and otherwise, are testing this type of a vaccination approach in patients with other cancers like lung cancer, bladder cancer, kidney cancer, and I know now that this results have positive in melanoma, likely more cancers too.

• 5:19Speaker 00

  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?

• 5:31Speaker 01

  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, and 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

• 6:13Speaker 01

  is high in the melanoma field because there are a lot of mutations 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.

• 6:26Speaker 00

  As 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?

• 6:42Speaker 01

  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 the 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 the immune response, and then the vaccine drives that immune response to the specific neoantigens in parts of the tumor that are relevant for that one individual patient. So it's a very welcome combination. It makes scientific sense to combine them.

• 7:27Speaker 01

  In the future, one could think about 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 type of a vaccine with KEYTRUDA against other standard treatments, potentially even including chemotherapy in certain malignancies.

• 7:44Speaker 00

  You said that not all the data has been released yet. What will you be looking for once that final data comes out?

• 7:52Speaker 01

  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 back 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 that 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

• 8:36Speaker 01

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

• 8:42Speaker 00

  Whenever we talk about a drug, we talk about possible side effects or drawbacks to this approach. Are there any here?

• 8:49Speaker 01

  Remarkably, this therapeutic vaccination approach is very well tolerated. It has not increased the rate of immune therapy toxicities otherwise that one might see with KEYTRUDA 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 3 results. But in general, with the earlier experience with this and treating patients myself in this particular trial, anytime you inject somebody with a shot, there is some redness or soreness where 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 had was a little bit of fatigue and some chills or mild fever after the injection for a couple of days.

• 9:30Speaker 00

  Of course, when people hear about this story, 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?

• 9:41Speaker 01

  We still need to see the results of the Phase 3 trial, and the FDA has not approved this at 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 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, for patients to keep in mind is, this may be something to talk to your doctor and see if a clinical trial might be appropriate for you, but at the moment, this is not something that can be routinely administered.

• 10:19Speaker 00

  Now, 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.

• 10:30Speaker 01

  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 you 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 confidently that the odds of surgery and treatment being punitive for them in the long run have now been shown to be increased, and we're delighted with that information.

• 11:11Speaker 00

  Dr. Pastow, thank you for taking time to be with us today. Very interesting stuff.

• 11:15Speaker 01

  Thank you very much for having me. It's a pleasure.

• 11:17Speaker 00

  Dr. Michael Pastow, Chief of the Melanoma Service at Memorial Sloan-Kettering Cancer Center in New York. This 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, 8774-CY-FRY. That's 877, the number four, CY-FRY. Our listener line is always open. I'm Ira Flatow. We'll catch you next time.