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Momelotinib Clinical Trials: What Should I Know?

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Published on July 31, 2020

MPN Momelotinib Clinical Trial: What Do Patients Need to Know?

 In this segment from a recent MPN Answers Now program, host Andrew Schorr discusses the MPN momelotinib clinical trial with experts Dr. Christopher Hillis from Juravinski Cancer Centre in Ontario, Canada and Dr. Barbara Klencke, chief development officer at Sierra Oncology as well as other MPN trials in development. They are joined by MPN patient Marilyn Lidor, who has participated in a trial and her husband Dov, who offer a message of hope.

This is part three of a three-part series. Watch Part 1 here and Part 2 here.

This program is sponsored by Sierra Oncology. This organization has no editorial control. It is produced by Patient Power in partnership with the MPN Research Foundation and BagIt Cancer. Patient Power is solely responsible for the program content.

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Transcript | Momelotinib Clinical Trials: What Should I Know?

Andrew Schorr:
Dr. Hillis, I got to put you in the hot seat, first of all, just a Canadian question, someone is an MPN patient in Nova Scotia and said, "Well, we're in Halifax. Can we participate?"

Dr. Hillis:
Yeah. I don't know if Halifax is a site or not for this particular clinical trial. There are a few MPN-treating physicians who work out of Halifax at the QEII, if that's where they're getting treatment, and if this clinical trial is not available there, another one might be.

Andrew Schorr:
Okay. But can somebody from Halifax, sometimes, let's say, if you're an investigator for the trial we're mentioning, come to you and then still take the medicine at home and get some local blood tests, like even what Marilyn was saying, she gets some blood tests close to home?

Dr. Hillis:
Our particular site's not set up for that and, unfortunately, if somebody's living in Halifax right now, every time they went home from Hamilton, they'd have to quarantine for two weeks because of travel due to COVID, and so that makes things like that even more difficult. But, yes, there are centers in Montreal, in Toronto, that will often see what we call out-of-province patients for clinical trials.

Andrew Schorr:
Okay. All right. We've got other questions for you. This one may be for Barbara. Dr. Klencke, whether it's your medicine or others, there had been a fear and maybe, for some people, this question is still going on, do some of the ingredients get made in China? And so is there worry that there's something that could be in the ingredient for the drug, trial or not, that could be worrisome? And, obviously, we know the pandemic is worldwide now, but they know that a lot of drugs or components of drugs are made in China. Do you want to comment on that briefly?

Dr. Klencke:
Well, I would say that regulating authorities, like FDA or others in other countries, not only watch the protocols very carefully, they certainly review all of the data that comes from protocols very carefully, but they have a whole entire branch that looks at drug substance, drug product, and, actually, the chemical make-up of drugs, and we know that we have to be accountable for the quality of the drugs that we provide to patients. I think that all of the chemistry and things like that are extremely well worked up.

Andrew Schorr:
Okay. What about supply? Because, let's say, everything is wonderfully squeaky clean, but if components are being made in other countries, depending on how we shut down in different places, are you worried about supply?

Dr. Klencke:
Well, luckily, we have plenty of momelotinib supply. Our randomized trial, though, one-third of patients will be randomized for at least a period of a few months to a control arm, and so we're not as in control of that supply. We have to purchase that. We have worked very, very hard to ensure that we have sufficient supply there. We have to watch that whole process.

Andrew Schorr:
And I should mention to our audience that that's what I've heard from the other drug companies, and the companies, Bristol Myers with fedratinib (Inrebic), and ruxolitinib (Jakafi) from Incyte, and Novartis and all that, they're not worried about supply for us. I just ordered a refill today.

Okay. Here's another question, probably for you, Dr. Hillis. Let's see if I've got it right. "I've had a bone marrow biopsy. I have polycythemia vera. I do not know if I have a mutation," so they don't know, and they do know that they have JAK2 negative, but they don't know about other mutations. What trials are going on looking at mutations, like you mentioned calreticulin (CALR) and you mentioned MPL? Are there trials going on related to these other mutations too?

Dr. Hillis:
Always hard, without looking at the bone marrow myself, to make a comment on all the details. But, in general, for folks who have rarer subtypes of what is already a rare disease, there's very few interventional trials or drug trials for those conditions, but what there are is a number of registry or observational studies across North America and Europe that folks, like this particular person, I would highly encourage to enter into. Observational studies and MPNs are a particular interest of mine and it's only once we get a critical mass of five or 10 people with a particular subtype of a subtype, which is what this person sounds like they may have, we could start to answer questions and, even in early days, if we can only answer those questions in an observational way, meaning without, say, putting them on a drug, we can at least start to generate some ideas of trials we could do in the future. And so, no, unfortunately for the very rare subtypes of polycythemia, there are not trials in Canada for sure. I would say that a registry would be a good first step for getting involved in research.

Andrew Schorr:
Okay. If somebody is JAK negative though, does that mean a JAK inhibitor has no role?

Dr. Hillis:
No, that's not true, which is a good thing. With polycythemia, most folks carry the JAK mutation. With myelofibrosis, only about half of folks with myelofibrosis have the JAK mutation, and that's a reality of the disease. But in spite of that, there is still a clinical benefit to the JAK inhibitors because it turns off the things that cause the symptoms, the inflammation and big spleens that can happen with these conditions regardless of if you have the mutation.

Andrew Schorr:
Okay. Dr. Klencke, here's a question for you briefly, and that is this patient has PV, lives in Southern California, where I normally am, and is anemic. Is your trial only for people with myelofibrosis, first question, and second of all, if it could include somebody who's anemic with PV, are there sites in Southern California?

Dr. Klencke:
Well, we have sites in Southern California, yes, but we do not enroll patients with PV, and part of the reason, there had been a prior study of momelotinib in patients with PV and most are not anemic, most have too many red cells and you give them a drug which increases red cells, the hemoglobin, and it actually was not effective because of that anemia issue. No, we don't. We need myelofibrosis. You can have polycythemia vera and transition to myelofibrosis and then it's just fine.

Andrew Schorr:
Dr. Hillis, I don't want to leave our friends with essential thrombocythemia out, and this was brought up by our producer, there are trials, there are two, here's one that came up, IMG-7289, I'm not familiar with it, but different trials in ET trying to see if there's something for people who can't tolerate hydroxyurea (Hydrea), Pegasys, etc. Where are we in helping ET patients, Dr. Hillis?

Dr. Hillis:
Yeah. ET trials are few and far between still, and for those who've kept up or have ET and kept up on the literature in ET, we've had some disappointing results in the last five years with the JAK inhibitors and other agents in ET, and so there's a number of centers of excellence in the U.S., in Canada. But, unfortunately, most trials require to open up that you're able to get even three or four patients on those trials, and with a rare disease, it's sometimes hard to find three or four patients. And I work in a center where we serve 2.1 million people in our catchment area, and for Dr. Klencke's trial, we may only be able to get one or two patients on it. And so, if you have the means to travel and you have ET, I'd certainly support someone getting on a trial like the one mentioned.

Andrew Schorr:
Okay. Let's mention, and I'll start with you, Dr. Hillis, here's a question we got related to just criteria, I guess, for this momelotinib trial. They want to understand, do you have to be currently on blood transfusions and have myelofibrosis? What's the inclusion criteria, basically?

Dr. Hillis:
You do have to have myelofibrosis. You do not need to be on transfusions, but your hemoglobin has to be low. And I know the Canadian units and not the U.S. ones, but Dr. Klencke can clarify that for the person who's asked the question.

Dr. Klencke:
Yeah, the limit is 10, 10 or less, grams per deciliter in the U.S.

Dr. Hillis:
Thank you, translating it to American for me.

Andrew Schorr:
Okay. And then one other thing about combinations, so, Marilyn, you're on the constellation drug CP-

Marilyn Lidor:
It's CPI-0610

Andrew Schorr:
... okay, combined with Jakafi or ruxolitinib. What about other trials, Dr. Hillis. If combinations could be the future, somebody asked about, "Well, what about combining with Pegasys or interferon?" What are the combinations we're looking at now?

Dr. Hillis:
Across the MPN spectrum, and the trial that Marilyn is on is a great example of how we design these trials, and so if you're going on a drug for the first time for an MPN, if you have ET or PV, that drug might be hydroxyurea or interferon, we can't compare people to not being on those drugs because that's really the standard of care and, in Dr. Klencke's trial, danazol (Danocrine) may be considered, not the standard of care, but a treatment you might want to use in that situation. And so, if we have a drug that we want to see if it has activity to do better by our patients, then we'll often add it to the backbone, ruxolitinib, hydroxyurea, or interferon, and there's trials with all of those backbones happening all across the world with combination agents that are very early in their development or, in Marilyn's case, a drug that's a little more mature in its development.

Andrew Schorr:
Okay. I'm going to throw one other one in that I've just been hearing about. I also have chronic lymphocytic leukemia, and there's a drug that was developed there called venetoclax (Venclexta) and there was a similar but different drug, navitoclax, and so I understand there's research going on with navitoclax maybe combined too, so they're yet another combination, right?

Dr. Hillis:
Yeah, and the combination trials that excite us, and this would be an example of that, is where you take a drug, like a JAK inhibitor that we know does a great job to help a good number of patients, but then you attack the MPN in a completely way. I think you called it the one-two punch earlier in the program, and that would be another example of a one-two punch situation. It's also taking a drug or a class of drug that your doctors are already familiar with because CLL treatment has BCL-2 inhibitors like venetoclax and so we have some comfort using those agents so that it's more straightforward putting them into a clinical trial.

Andrew Schorr:
Okay. First of all, Barbara Klencke, her company Sierra Oncology, has a different molecule, I think you guys call it, in the JAK class, to see if it can help people this specific situation, anemia, okay? That's one kind of brother or sister. The others that are approved or others in trial may be different, so they help different subtypes of MPN patients and then, overall, Dr. Hillis, we may be looking at, like Marilyn's situation, can we have the one-two punch on top of that to do even better? Chris, did I get it right?

Dr. Hillis:
Perfectly.

Andrew Schorr:
All right. I want to get some closing comments. Let's start with you, Dr. Klencke. First of all, as someone really leading, worldwide, the work going on and the development of a potential new drug, what do you want to say to patients to consider being part of a trial now? What would you want them to ask about with their doctor?

Dr. Klencke:
Yeah, very good question. I do think knowledge is powerful, knowledge of the disease, knowledge of what the options are, knowledge of how likely a clinical trial therapy might match your situation in terms of what are your major problems that you're facing with your disease, and what is the likelihood that the drug is going to either be safe, both safe and potentially effective, so just understanding what it has to offer and comparing that to what you could get outside of a trial.

Andrew Schorr:
Well said and, as Dr. Hillis was saying, MPN patients, myelofibrosis, we're different. We're not all the same. I had a conversation I just wanted to share briefly with a woman here in Northern California, who now has a very enlarged spleen and very low platelets. For example, there's a trial of another drug, pacritinib, aimed at that population, so I was trying to help them learn about that. Yeah, some patients have anemia, some have low platelets, what can be right for you? Okay. Well, thank you for being with us, Dr. Klencke.

Dr. Hillis, what do you want to say to our MPN audience about at least considering being in a trial and a conversation they might have with their doctor or research they might do to see could that help them and the community and you, as a researcher moving forward?

Dr. Hillis:
Yeah. I want to thank the patients and their care partners, so the Marilyn and Dovs out there, because we won't be able to treat the folks who come after Marilyn and Dov into our clinics. We know the next person in the waiting room, if it wasn't for people like Marilyn and Dov being so kind to volunteer their time and energy towards being in clinical trials… Not everybody will be eligible for clinical trials. We heard some examples of that in the Q&A session and so, if patients want to better inform themselves, most cancer centers, on their websites, mine would be an example, post right on there what clinical trials are available at our site. There's large national websites that say what clinical trials are running where and to look out for that.

But MPNs are very, very individual diseases. There's 1,000 MPN patients and there's 1,000 different variations on their disease, and so I don't want folks to be discouraged if they can't get into a drug trial or an intervention trial. I encourage them to ask their doctors about what registry they could maybe be involved in or what non-drug intervention trials could maybe be tried for them because, really, just as much as Marilyn and Dov are contributing to science and our knowledge, being in those sorts of trials also greatly contributes to science. And so thank you to everybody who's joining today and all the patients out there who even think about doing a clinical trial. It's what we need to do to better care for our patients.

Andrew Schorr:
Well, I think we need to say, as patients, thank you to you, Dr. Hillis and Dr. Klencke. Dr. Klencke, thank you for your company stepping up, getting investment, so you can try to really fill an unmet need that we have for patients. And, Dr. Hillis, working across many trials and seeing lots of patients there in Canada and participating globally, thank you for what you do. You guys are our angels, okay? Thank you.

Dr. Klencke:
Well, we appreciate your work in spreading the information that you do and all of the support you provide to people with these diseases.

Andrew Schorr:
Thank you. Okay. Marilyn and Dov, so first of all, Dov, as an advocate, it really helps for, whether it's in Canada or North America or worldwide, I think there's power in us coming together to have these discussions. Wouldn't you agree that knowledge is power and it may be approved therapies, it may be experimental ones, right?

Dov Lidor:
Absolutely. Knowledge is definitely power. Andrew, when we first got to know you, I think that's what strikes first, the word knowledge is power, and you gave us the power, so thank you for that. You gave us also the hope. I mentioned that in our discussion in Miami and it's more true now than ever. Hope is the key word.

Andrew Schorr:
Well, thank you. Marilyn, you're doing better. You've been participating in a clinical trial now for nine months. Are you hopeful about the future, not just for you, which is important, but also for the rest of us in the MPN community?

Marilyn Lidor:
Yes, I am. I've gone from one end of the spectrum to the other, really, in the last nine months, feeling very tired and not well, to totally a different person. I have to mention that I was also inspired by you, Andrew, because you, all along, have said that we should be open to clinical trials and you yourself were on one, I think, for CLL, and then you were on that drug for many years and it helped you for many years. This is one of the reasons I also joined the clinical trial because of what you said.

Andrew Schorr:
Thank you. Well, we can all help each other and, right, I've been in two clinical trials, actually, and the myelofibrosis was discovered by being in a trial for a blood thinner and they said, "Something's out of whack," and I was really lucky that there was ... that's when Jakafi first came out, that it was there. I don't know how long the medicines I'm on will work, so what you're doing, or if I become anemic and what Dr. Klencke's working on, or something else that Dr. Hillis has up his sleeve there, that may be next, and so I urge our community to consider trials. It should always be on the table, even if something's working for you and you were on a one-drug therapy for a while, it worked for a while, I'm on one drug, well, will we need something else? That's always part of the discussion I have with my doctor.

Thank you so much for all of you being with us. I'm Andrew Schorr. Remember, knowledge can be the best medicine of all.


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