Should You Join a Myeloma Clinical Trial? Phases, Benefits & How to Find One

Dr. Joe:
So for this presentation, I have but one slide. And we would like to talk for a few minutes about clinical trials. What better segue to talk about clinical trials than what I just shared with you about the ... And I'm very proud of myself that I can do this so well. The trispecifics is this one slide. I was saying to Heather earlier, I think I'm sort of dating myself here. When I was younger, there was a show, I think it was a Canadian thing. I think it was kind of the Canadian version of 60 Minutes and it was called W5. And they would have a particular topic and they would tell you what, why, who, when, and where about this particular topic. Well, let me give you the quick W5 of clinical trials and then we can move to our Q&A and then enjoy the white, red and rose waiting for us outside.
So what are clinical trials? Well, clinical trials are why we are here today in multiple myeloma. If it were not for clinical trials, all these new drugs I described to you, the monoclonal antibodies, the bispecific antibodies, CAR T-cell therapy, antibody drug conjugates, trispecifics, in vivo CAR-T, all those things of course wouldn't exist. So clinical trials are the way in which we introduce new drugs into the system. Now there is of course a terrible history of clinical trials in this country and I'll come to talk a little bit more about that tomorrow and later in the talk. But nonetheless, this has been the mechanism and it is built with tremendous now protections based on our terrible history to ensure that we are not treating people like guinea pigs as it were. We are trying to provide them an opportunity for new and better therapies. And so clinical trials are designed in such a way under very careful regulation to ensure that we can, in a safe manner, introduce drugs into any particular disease.
And when I say safe, that is always the primary modality. Any medical student, resident, fellow who works with me in my clinic, I always say my three word expression, "Safety is paramount." It is the most important thing we do. Yes, we want efficacy of course, but as we develop these drugs, safety is paramount. And so I'm going to describe to you very quickly what we call the phases of a clinical trial that are designed to ensure that when clinical trials are introduced, safety is paramount.
So we start with what's called a phase one clinical trial of which the first is sometimes called the first-in-human. And this is the kind of clinical trial that I have the privilege of doing where we test a drug the very first time it's ever been given. We were talking earlier about Sarclisa or isatuximab. I had the privilege of treating the very first myeloma patient on the planet with that drug almost 15 years ago. And here, yes, we want to give a drug that is promising to a patient. Before it even gets to a patient, we've tested it in the lab. We've tested it on myeloma cells and we've tested it on mice. As I've said at many of these meetings, you'd be a little creeped out if I told you how similar you are to a mouse, but that's another discussion. But really we can test these things to get a sense of how they may work and how they may cause side effects so that when we come to humans, we can be pretty confident that we can deliver this safely.
But to be uber careful, typically at the first-in-human phase one clinical trial, if we think, let's say, I think this drug's going to work at 10 milligrams, we give half a milligram. We give a very, very low dose the first few doses. We can often dose escalate within that patient, but we want to start really low because the goal of a phase one trial is to ensure that the drug is safe and to find what is the right dose to go forward into a phase two trial.
In a phase two trial, we test it in a larger group of patients saying, okay, you know what? We actually do think that 10 milligrams is the right dose in this patient. Now let's treat 100 patients and see how well it works. And we have some kind of threshold. We'll say, if it doesn't work in 25% of patients, there's no point going forward. But we work at, oh look, 40 out of our 100 patients responded to this drug in this way. So now we feel that this drug shows efficacy, meaning that it's effective. We understand the safety profile. We can manage that carefully. Sometimes drugs don't get past that phase. We've had some drugs that, well, the side effects were just too significant or the efficacy was not high enough at a predetermined threshold. We just say, look, we say if we don't see this, say 25% or whatever percent we've chosen to work, then we have to drop it.
But if it does go forward, then it comes to the highest level of clinical trial, what we call a phase three trial where now we're comparing whatever strategy we think works compared to what is already the standard of care. So if the standard of care is already a combination of drug AB, and I'm testing this new drug C, then the clinical trial might be AB versus ABC. Does adding C to AB make that situation any better? And so we often see these clinical trials that compare three drugs to two or sometimes three drugs to three. There's different ways of doing it. So if your doctor or your healthcare team is talking to you about a clinical trial, it's helpful to say, "Is this a phase one trial? Is this a phase two trial? Is this a phase three trial?" The earlier phase, fewer patients are being treated with greater focus on safety. As we go higher, we go into more patients.
That being said, in a phase three trial, typically those two arms, you don't get to say, "Oh, I want to take ABC." We are randomizing patients, which literally means that patients don't get to decide in advance. If you're going to accept the trial, you either get AB or ABC. Sometimes you don't even know which one you're taking, you're so-called blinded to it. And that's to make sure that we're not introducing any other bias towards it.
Why would we do clinical trials? Well, this is maybe the point that I find most important to emphasize because very often when we talk about patients going on a clinical trial, they start saying things like, "Well, I want to help the myeloma community at large and I want drugs to be developed and I want the next generation of myeloma patients to ..." Okay, love your altruism. And I'm not trying to demean that, but it's really about you. Why would you go on a clinical trial? For your benefit. We've shown unequivocally centers that have clinical trials have better outcomes for their patients. I can't begin to describe to you, and it makes me emotional to think about it. Literally the thousands of patients I know are alive today because of clinical trials that I've had the privilege of putting them on or our team has been able to put on.
So don't get all altruistic about clinical trial. You're not donating your body to science here. This is for you. We do clinical trials because we want patients to respond. We want to give them an opportunity. So you say, okay, here's this clinical trial with a trispecific. I could go on to a more standard therapy that's already FDA-approved, but this trispecific is very promising. It might give me a chance to get a drug that otherwise I wouldn't have opportunity to give. If it works, great. If it doesn't, then I can go on to the more standard therapy. That's the conversation we often have with patients. Does it match? I like the fact that this is a treatment, this CAR-T I get once and then I don't have to have any more treatment. We have to match that. You're going to hear tomorrow in particular about this notion of shared decision-making, which is so important.
And I believe that the IMF's Nurse Leadership Board has really been the tip of the spear of this topic of where you don't just go in and the doctor says you'll take it and you'll like it. This is where we match all the options we have and boy, we have options with myeloma now with what is your preference and match them together. So the why of clinical trials is for your benefit, not for someone else's benefit. And always remember that as you're considering a clinical trial.
Who should be on a clinical trial? Well, we want more and more people to have access to clinical trials. Historically, there's been terrible under-representation of certain groups to have clinical trials, whether it's geography, race, ethnicity, gender, all of those sadly have been barriers in the past, in particular within the African American community. 20% of myeloma patients in this country are African American. Most clinical trials have enrolled between 5 to 6%. Lots of reasons for that, of course. We'll talk a bit more about that tomorrow in our program or the IMF's program that has developed to try and improve that, but we want access for all. Clinical trials should not be viewed as some boutique, very separate approach. It should be standardized as mainline approach. And more and more, we think of here in LA, we think of the big centers like the ones that are going to be represented by the other docs here, City of Hope and Cedars-Sinai and USC and UCLA.
I mean, you have amazing centers here, but it's also amazing to see that more and more clinical trials are now making their way into smaller centers where they're more accessible or how some of these centers are building satellites like in Orange County where they're making more of their clinical trials available. That becomes so important. That's one of the things we're particularly passionate about, and you're going to hear more about this from Heather tomorrow and the plans that the IMF has to expand its portfolio to facilitate greater representation in clinical trials.
Well, when should you think about a clinical trial? Most people think this is kind of like, I mean, football season did start this week? Anybody with me? Is this thing on? Okay. They think of it like the Hail Mary pass. "Oh, I guess I'll think about a clinical trial when everything else has failed and I have no other option." Well, we do offer that and there are a lot of patients who come to see us when they have exhausted all options, but that's not when you should start thinking about a clinical trial. We have clinical trials now at all phases and stages of myeloma, from smoldering myeloma to newly diagnosed, to first relapse, second relapse, all along the way. And not always, I mean, we're talking mostly about so-called therapeutic clinical trials now, but there are other kinds of trials or supportive care trials saying, "Oh, is this vaccine better than that vaccine? Should we give this antibiotic for this long versus that long? Can we give this to support your nutritional status? Will this NUTRIVENTION study that Dr. Urvi Shah did?"
So don't always think of a clinical trial as just being a new kid on the block drug. Think of it sometimes as supporting the lifestyle and the journey you have in multiple myeloma. So clinical trials should not only be thought of at the very end. For example, right now in frontline therapy, there are great clinical trials going on saying, "Hey, could we replace stem cell transplant with these new CAR T-cell therapies and bispecific antibodies? What if we combine two different bispecific antibodies together or these trispecifics and others that I've discussed?" So don't only think of clinical trials as if you will, the final Hail Mary pass.
And then lastly, where? Well, as we've said before, I think we are moving in an era in cancer in general, and I know particularly in myeloma where we're trying to have them more accessible to all. Thankfully, the IMF has partnered with an organization called SparkCures that you may have heard about. And it's easy if you go to the IMF's website, myeloma.org/sparkcures, or even just look at the clinical trials button, it'll take you embedded within myeloma.org to this search engine where you can search for clinical trials. You can choose the geographical area and how far you may be willing to travel. You can choose it by if you're newly diagnosed, relapse, what treatments you've had before. It really is a sophisticated searching tool with multiple filters to help you. You can do it anonymously or you can register on it so that it can give you updates as other trials open and so on. It's really meant to be there to help you to find clinical trials because it is really amazing how many there are.
And if you go to clinicaltrials.gov, which lists them all. So if I go ... Actually sometimes I do this, before this talk, I didn't do it today, but very often I'll go to clinicaltrials.gov and I'll type in multiple myeloma, ding, and it'll come up with 4,826 clinical trials. Are you going to read through all 4,800? It's not going to be very feasible to do that. So this search engine that's been developed by SparkCures is really beneficial to be able to facilitate that.
So I know this has been a rapid fire overview of clinical trials, but if there's a take home message, it is this, that clinical trials are there to help and to provide opportunities that might not otherwise be there. Yes, they come with risks. Yes, they come with benefits. The discussion, the conversation with your healthcare team, because you have to consent and to be consented, you have to be informed. That's why we call it informed consent. You shouldn't just be told you're going to take this trial without being given all of the elements of it. How many times do I have to go in? How does this affect my insurance? Thankfully, more often than not, insurance is not a major issue with clinical trials because more often than not, the company running the clinical trial has to provide you anything that would not be normal standard of care treatment.
So if you want to learn more about it, as I say, go to the website, you can search SparkCures and of course we're always available for your Q&A. And on the subject of Q&A, I believe it's time. So I will turn it back to Heather to guide us and we will open the floor for Q&A for all of our speakers for this afternoon. Thank you so much for your attention.