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The PancChat Podcast is a collaborative effort from Let’s Win Pancreatic Cancer and the Pancreatic Cancer Action Network (PanCAN), inspired by the long-running #PancChat Twitter/X chat.
Hosted by award-winning journalist Alisyn Camerota, each episode features conversations with leading researchers, clinicians, patients, and advocates who are shaping the future of pancreatic cancer care and research. Together, we deliver expert insights, personal journeys, and the latest breakthroughs—bridging the gap between science and lived experience.
Whether you’re a patient, caregiver, healthcare professional, or simply want to learn more, join us to connect, be inspired, and learn how you can help to accelerate progress in the fight against pancreatic cancer.
Julie Fleshman: Hi. I'm Julie Fleshman, president and CEO of PanCAN. On today's podcast, we will learn about immunotherapy and personalized treatments for pancreatic cancer.
Alisyn Camerota: Hi, everyone. Welcome to PancChat Episode 20. I'm your host, Alisyn Camerota. In the last episode, we learned more about the vaccines that are being developed for pancreatic cancer. Today, we focus on immunotherapy and personalized medicine.
Vaccines also play a role in this category of treatments, so we'll get into that. We want to thank our sponsor, Revolution Medicines, for their help with this. Let me bring in our guests. We have Dr. Elizabeth Jaffee with us.
Dr. Jaffee is deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and chief medical advisor of the Lustgarten Foundation. She's an expert in the field of immunology. She and her team focus on bringing this revolutionary approach to treating pancreatic tumors. Dr.
Jaffee, thanks so much for being here.
Dr. Elizabeth Jaffee: Thank you for the invitation.
Alisyn Camerota: I've been looking forward to talking to you. Okay. So let's start with immunotherapy and help everyone to understand this. My understanding is that immunotherapy has been a game changer in many different cancers, but so far has not made very impressive inroads in pancreatic cancer. So what's the problem?
Dr. Elizabeth Jaffee: Right, exactly. Great question. So immunotherapy works in about twenty to twenty five percent of cancers right now. Some of the bad cancers like lung cancer, we were very surprised initially that it works so well in lung cancer patients. And what we've learned over a very short period of time actually, is that the patients who are responding to the current FDA approved immune agents, and these are immune modulators.
What they do is they work on immune cells that get into the tumor, and they have the ability to kill the tumor, but they get turned off by the tumor. So these immune modulators actually prevent the stop signal on the immune cells so that they can kill the cancer. So why does it work in twenty percent of patients? Because those patients have tumors that have many mutations in their cancer, genetic mutations. And these mutations are continually recruiting new immune cells saying, Hey, look at me.
It's like a viral infection. It's a new signal within the tumor that's saying, Hey, look at me, do something about it. Because that's what the immune system does. It comes and clears viruses or infections. So these T cells get there, they see those, we call them antigens, they see these tumor proteins that are unique to the tumor and they want to kill it, but then they get stopped by the tumor.
The tumors are very smart. They secrete proteins that inhibit these immune cells from working. So you give these immune agents their antibodies that can block the signal that the tumor is giving to the immune cells to stop them from working. So they work. The problem is eighty percent of cancers don't have lots of mutations, pancreatic cancer being the example of such a cancer that does not have continuously changing mutations.
They have very few. And in fact, the most critical mutation is mutated KRAS. Mutated KRAS exists in over ninety percent, some have reported ninety five percent or more of pancreatic cancers. Well, the cancers are very dependent on this one mutation. Certainly other mutations occur, but not to the point where they're continually turning over to alert the immune system.
So we never get an immune cell coming in. We don't even get an immune cell to realize that the tumor has these proteins. It's totally masked, these proteins. So that's where a vaccine comes in. If you know what antigens you're trying to activate an immune response against, and that's again, proteins expressed by the tumor that's unique to the tumor, the pancreatic tumor.
We can make a vaccine systemically, we can then activate the right immune cells. And by using a vaccine, it actually activates good immune cells. So these immune cells, I like to call them they're fit. They're fit to actually recognize cancer and kill it. They have the machinery, they're very fit.
And then they get into the tumor, you still need these immune modulators because they can still get stopped. But now at least you're getting the immune cells in. Now you give it with one of these other immune modulators and now we start to see the cancers being killed. Now that's simplistic because, just because, and the most common one that we've seen FDA approved is something called anti PD-one or anti PD L1. And there's a number of different companies with different company names, but the generics are anti PD-one and anti PD L1.
That's not enough in pancreatic cancer. So many of us in the field have been studying in small cohorts of patients our vaccine with different immune modulators. I think we finally know the right combination in at least a subset of patients. And our group has been testing this now for quite a while. And there's a group at Penn that has found yet another signal and they've been testing.
That's also looking pretty good as well. So, but the vaccine is needed to get a fit T cell to be able to even start that response against the cancer.
Alisyn Camerota: Well, is very interesting to me, Dr. Jaffee, because obviously it sounds like this is kind of the wave of the future. But it's my understanding, and maybe you could help everybody really process this who's listening. So far, the vaccines have to happen very early in the diagnosis or in the process. And as we know, part of the tragedy of pancreatic cancer is it's often diagnosed at stage four.
So I think, correct me if I'm wrong, the vaccines are not helping if it's stage four, but where are you seeing the most promise?
Dr. Elizabeth Jaffee: Right. So the most promise we're seeing are in two, actually in three, scenarios. The first is, patients who are surgical candidates who undergo surgery, and then we give the vaccine after they undergo standard of care, which is usually chemotherapy, sometimes radiation. And we're finding that patients are not recurring after that, a subset of patients, not every patient, but a good number of patients. Again, small studies, we need to do more studies, but that is a good place because we call it minimal residual disease.
We can't see any cancer when we do CAT scans, but we're worried that there are little seedings that are microscopic. The second area where we also are looking at this, which is turning out to be very helpful in trying to get the best combination, is in the neoadjuvant and adjuvant setting. So what does this mean? This means there's surgical candidates, patients come to us, they can have surgery right now, or they can wait a couple of weeks, get immunotherapy first and then go to surgery. And we're finding that our vaccine given with this one antibody, anti PD-one plus another antibody called anti CD137.
So these are two antibodies. The first one, PD1, takes the stop signal, it inhibits the stop signal on the vaccine induced immune cell. The anti CD137 actually is a, I call it a supercharger. So it sees the T cell, it may not be the best T cell yet, and it kind of supercharges it to really kill the cancer. And what we're seeing in that setting is that we're seeing the immune system actually causing regression of tumors before they even get the surgery.
So when we take the tumor out, a lot of the cells are gone. In some cases, we don't see the cancer. Now it's small studies, but the point being, we are really on the verge, I think, of understanding how we can make the immune system work against pancreatic cancer. The third scenario is one that we're very excited about and it gets to your point. You know, the best thing would be to prevent pancreatic cancer, right?
I would love to vaccinate everyone when they're 18 or 20 against pancreatic cancer and nobody gets it. That's been a dream of mine for thirty years. Well, we're finally able to test a new vaccine that we have that targets the first change in the normal cell that starts to cascade towards a cancer. And again, that's mutated KRAS. It's the first mutation or abnormal protein turned on in a pancreatic cancer, or in a normal cell that leads to pancreatic cancer.
And so we've been vaccinating individuals who are at risk for pancreatic cancer. So people who have small lesions on their CAT scans, we can't biopsy them, so we don't know for sure whether they're going to progress or not. And they have either a family history or a genetic predisposition. And so we've done 20 patients so far. Again, you have to start early, show two things, one safety, and the second is that we can induce an immune response.
We do induce a really good immune response so far for those patients who've made it out one in two years. We're seeing that immune response being able to maintain, which is critical. And that's the beauty of the immune system. You want it to maintain so that should another insult that starts a cascade of pancreatic cancer occur, the immune system can very quickly activate against it. We also are seeing some regressions on a few of the patients of the lesions that are on their CAT scan.
So it's giving us hope. Again, I don't want, we're not calling a victory. It's giving us hope that this may be a good way to prevent pancreatic cancer in the future. So we're hoping to do the next study to really understand how the vaccine's working and expand it to some other populations at risk.
Alisyn Camerota: Well, does sound very promising and it's fascinating. So would you start getting the vaccine? I know you were saying that your dream has been to vaccinate everybody. But would you start giving the vaccine to people, let's say children, let's say my children, kids of people who have died of pancreatic cancer or siblings of people who have died of pancreatic cancer? Is that where you would start?
Dr. Elizabeth Jaffee: I think that is where we would start. And again, when you show safety, then there's really not a downside to it. So what we do need to make sure of though, is that it's inducing a good immune response, but that's exactly the group of individuals that we would consider. And the immune system is so much better in younger people than it is. The older you get, the immune system isn't as good as it should be.
Alisyn Camerota: Well, that's amazing. That's a really fascinating cutting edge concept to think about and to hope for in the future. Let's talk about what exists now in terms of immunotherapy. So my husband had an opportunity to get into a clinical trial with immunotherapy right after he was diagnosed. We excited, very excited about it.
He did it. And we were excited about it because it seemed to have fewer side effects than traditional chemo. And again, here again, it was new and that seemed like it might work better than the standard of care. But they're not without side effects. So what people who want to do immunotherapy with pancreatic cancer, what are those side effects?
Dr. Elizabeth Jaffee: Yes, great question. So very different from chemotherapy and radiation. With immunotherapy, the side effects, so if you think about it, the immune system fights against infection, but you can also sometimes get autoimmunity with the immune system where it fights against normal cells. And so by unleashing the immune response in the way we're doing it with these immune modulators and then vaccine adding to it, you may not only be inducing a cancer specific T cell, but there may be in people who are at risk for autoimmunity, cells that could actually see, you know, a normal cell. So there are certain organs that we worry about in particular.
So colitis is a very common side effect. That's when the colon is affected and you get diarrhea. So patients are educated. As soon as that there's a change in their bowel movements, they call us, we can treat it. You know, it's very treatable and it's interesting.
We stopped the immunotherapy, until that resolves. And then believe it or not, they can go back on immunotherapy often and it doesn't come back again. We don't know exactly why yet, we're trying to understand. But the good news is, it usually does not inhibit the treatment from having a longer term response. There are other side effects as well.
You could get hepatitis, less likely. So anything, any inflammation of any organ can happen. The other organs that often are affected are the thyroid parathyroid. So, but again, we could replace thyroid with medications. So, none of these are, stop the therapy in the majority of patients.
And most patients call us with the earliest symptoms so we can intercept pretty early. But other than that, and maybe fatigue from long term therapy, if they're on long term therapy, a little bit of fatigue with like any medication and treatment, but people live normal lives, they really do. And I think that's critical. For me, I have to be honest, when I started treating patients, when I was a fellow, you know, in the early 90s, it made me so sad because patients really suffer from chemotherapy. And if we could do something that, you know, reduces that suffering, reduces the amount of time they need chemotherapy, you know, I feel like we've done something for patients.
Quality of life is critical.
Alisyn Camerota: Completely agree. Yes. I think that that is so important to say. You can still live a very good life and have a good quality of life as long as the treatment isn't doing harm to your quality of life. And so that's really good to hear about with immunotherapy.
And so, of course, sadly, with pancreatic cancer, we often measure success in terms of months, not necessarily years of survival. So are there clinical trials that have been proven to extend patients' lives even in terms of months with immunotherapy?
Dr. Elizabeth Jaffee: So far, we haven't had any immunotherapies for the majority of pancreatic cancer patients, except for one example. So I mentioned to you that there are cancers where the tumors are constantly making new proteins that can alert the immune system. So about one to two percent of pancreatic cancer patients have that genetic phenotype or a genetic type of cancer. Very unusual in pancreatic cancer, more common in colon cancer and ovarian cancer and endometrial cancer. But we do identify those patients early so they go right on immunotherapy.
Interestingly, although it's about a sixty five percent long term, treatment effect in colorectal cancer, it's only about thirty to thirty five percent of pancreatic cancer. So even, a better prognostic pancreatic cancer patient, we still haven't done as well with immunotherapy as we have in other cancers. But I think it's a start and it shows that immunotherapy can work in this disease.
Alisyn Camerota: Okay. So now let's talk about personalized treatment or medicine or precision medicine. So how is that different than immunotherapy?
Dr. Elizabeth Jaffee: So personalized, know, when we think about personalized, we think about treatments that are specific to one patient versus the entire population. But I would also say that there are subtypes that, you know, if you look at the number of types of cancers and you look at the subtypes, we have lots of technologies now that could take a look under the microscope and or do genetics and subtype cancers, even within pancreatic cancer, there's probably 200 different cancers. So putting into that perspective, you realize how hard this is, but it also helps us to think about the type of therapy for each individual patient or group of patients. And so in pancreatic cancer, actually, when you spoke with Vinod, he has done vaccines for a smaller group of patients who are eligible, where they do have more proteins being made by the tumor as tumor proteins. And so you can make a vaccine that targets a patient's specific mutations, but that's a small group of people.
We're doing vaccines where you can target the KRAS mutation because there are six different mutations that cover most of the patients. And so it's easy for us to subtype those groups and give vaccines that are specific to the smaller group of patients. Now, targeted therapy is part of precision medicine. And so we're very excited about a new class of medicines, these KRAS inhibitors. And so there are a number of different companies.
Revolution Medicine is probably the one that will be the first to get the drug approved, showing a lot of benefit to even late stage patients, up to anywhere up to ten months of progression free survival. Doesn't sound like a lot, but it's a big progress and these drugs also are not as toxic as chemotherapy. So patients have a better quality of life for those ten months and there are people who go longer. But this is end stage pancreatic cancer failed everything. So we expect it's going to be even better giving it a bit earlier, in newly diagnosed pancreatic cancer when they become available.
But the interesting thing is that these drugs can actually early on alter the tumor to make it more inviting to the immune system. So, we and others have done studies in preclinical models showing that actually immunotherapy can synergize, can work together with these drugs. Well, why would you want to do that? Well, drugs only have a certain lifespan before you get resistance. We want to prevent resistance.
So you give these drugs, you reduce the burden of the cancer, and then you add immunotherapy. And immunotherapy, what's beautiful about immunotherapy is not only can it help kill residual tumors, but the immune system has the ability to adapt very rapidly. And we call it memory responses. So it gets a memory so that if the cancer tries to come back, immediately the immune system tries to respond. So that's the next step here is to see how can we combine these drugs with other agents that are specific to changes in a patient's given tumor.
Alisyn Camerota: That's really exciting. I mean, so such optimistic news that you're describing. So let's help our listeners understand how they can access this. Are there clinical trials right now that are available to patients out there with the combo that you're describing or even individually precision or immunotherapy?
Dr. Elizabeth Jaffee: Right. So I think right now they're at the individual drug stage. So we have many trials that are testing these KRAS inhibitors. A number of different companies have different inhibitors that are all showing good activity in different, in pancreatic cancer patients. And some of these companies are also testing them now earlier, realizing that in later stage it's working.
So as they move to get it approved, they can start clinical trials in earlier stage. So I would say all over the country, there are trials available. PanCAN is a great resource. Let's Win is a great resource to help navigate patients to trials that may be in their region. So I really suggest getting that information if you can.
And there's going to be a next wave of trials coming. I know that for a fact, many of us, you know, the pancreatic cancer community is, we're very collaborative. We work together, we help each other to fight this disease because this is a bad disease. And so many of us have a number of different trials we're developing, to integrate with these KRAS inhibitors so that we can see an extension. Right now, don't have a study that's ongoing.
We're getting ready, personally, I'm getting ready with my team to open up such a study and, we might do it with one or two other centers if we can.
Alisyn Camerota: Excellent. I'm sure a lot of people would be interested in getting into your study. So again, for patients who want to enroll right now, you suggest talking to the doctor.
Dr. Elizabeth Jaffee: Absolutely.
Alisyn Camerota: Dr. Jaffee, I thought it was so heartening when you and I were speaking off camera before this, and you were just sharing why this moment in your entire career of the past thirty years is so encouraging. So could you just tell our listeners about that?
Dr. Elizabeth Jaffee: Absolutely. So I'm going to preface this by saying, it's been a very hard disease to treat and, you know, you get to know the patients, you feel you're part of the family and it's devastating. I know it's devastating for the families. I've had it in my family too. And it wasn't until the past couple of years that we started seeing drugs that are active against this cancer.
And, you know, I have to give a plug to the Lustgarten Foundation for funding a lot of the basic science research and all of the work that PanCAN and Let's Win have done to really advocate for more funding. When I started, there was very little funding in pancreatic cancer. So this is a time where finally all of this information is leading to these new drugs and to see people with advanced disease responding, responding, and they're not feeling sick like they do from chemotherapy, they're having decent quality of life, even if it's for ten or twelve months, this is a big advance. And in my mind, this is the start of really making a big impact in this disease. Because once you have something working, you start to understand what are the resistance mechanisms?
Why did it stop working? Why isn't it working in this patient, but it's working in all these other patients? And then you could really modify these drugs to make them work in everybody. And hopefully, you know, too distant a future, figure out how to deal with the resistance. So I'm more optimistic than I have ever been.
I really, I say to my trainees and my colleagues, this is a moment that we're in for pancreatic cancer. This is our moment as a community, advocates, patients, funders, researchers, we're all in this together and there'll be nothing better than to see a real impact where we turn a death sentence into a chronic disease that people can live with, with a good quality of life. Yes, I want to cure it too, but I'll be happy to start with making it a chronic disease like diabetes that people can live with.
Alisyn Camerota: Dr. Jaffee, the idea that you're saying that this is the most optimistic that you've been is such music to the ears of everyone listening, myself included. So thank you for sharing all of that. Thanks for all of the really important information and the encouraging news. It was great to talk to you today.
Dr. Elizabeth Jaffee: Thank you very much for inviting me.
Alisyn Camerota: Thanks to our listeners. Also, I'm Alisyn Camerota and I'll see you here next time.
Cindy Gavin: Thank you, Dr. Jaffee and Alisyn for taking the time to discuss with our audience the implications of immunotherapy and personalized therapy. I'm Cindy Gavin, CEO and Co Founder of Let's Win. If you or a loved one has been diagnosed with pancreatic cancer, navigating this journey can be extremely overwhelming, but you don't have to do it alone. Be sure to explore the resources available for patients and caregivers through Let's Win and PanCAN.
You could find PanCAN at pancan.org and Let's Win at letswinpc.org. Our sites continuously post the latest research and have available tools to help you find a clinical trial. Let's Win also has a doctor finder that allows you to connect with a specialist in pancreatic cancer care. Together, Let's Win and PancCAN are committed to guiding you through every step of the journey, offering support, information and hope. In our next episode, we'll be discussing earlier detection, blood tests and the use of AI.
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