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Medscape
10-07-2025
- Health
- Medscape
S2 Episode 6: A Futuristic Vision for Treating Myelofibrosis
This transcript has been edited for clarity. For more episodes, download the Medscape app or subscribe to the podcast on Apple Podcasts, Spotify, or your preferred podcast provider. Tania Jain, MBBS: Hello again, everyone. I'm Tania Jain, and we're in season 2 of the Medscape InDiscussion : Myelofibrosis podcast. This is episode 6, and we're very fortunate to have Dr Naveen Pemmaraju for this discussion on a futuristic vision of the myelofibrosis (MF) treatment landscape. Dr Pemmaraju, we welcome you to the podcast. Naveen Pemmaraju, MD: Thanks, Dr Jain, for having me. Jain: Dr Pemmaraju does not need any introduction, but quickly, Dr Pemmaraju is a professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center in Houston, Texas. He's also the inaugural director of the BPDCN — blastic plasmacytoid dendritic cell neoplasm — program and the executive director of cancer medicine for the MD Anderson Cancer Network. We would like to share the mic today with Dr Pemmaraju, asking him about his vision for the future of MF treatment. Let's start with where things are, and you can share about your engagement in a lot of the protocol development and therapeutics development. Which are your favorite developments in the field of myeloproliferative neoplasms (MPNs) in the recent past that you feel will stick around and we'll continue to hear more about them? Pemmaraju: Thanks for having me on. I think this series that you're doing is great for all the stakeholders for MPN education, so I applaud you and the team. I think this is an exciting era and an exciting time to talk about what you just mentioned. There are three or four hot-topic areas that I would love for our patients, caregivers, practitioners, pharma — everybody — to know about. One is in the early-stage MPN, in polycythemia vera (PV) and essential thrombocythemia (ET). This is an area where there hasn't been much drug development in over 20-30 years. I would lump them together as sort of before-you-get-to-MF. There are some nice developments there. There are some new classes of drugs — actual, real classes of drugs that are emerging that we didn't have 5 or 6 years ago. For example, there are the hepcidin modulators and mimetics in PV, essentially trying to restore normalization of the distribution of iron in the body system so that folks don't have too high of a hematocrit. That class of drugs, my goodness, already has four, potentially five or six, drugs in clinical trials, in either phase 1 or close to phase 1. Even in our ET there are some novel classes of drugs, including but not limited to LSD1 inhibitors, which are — can you believe — in phase 3 randomized frontline testing and trials. For folks who think there hasn't been much movement there, I would highlight that. And then in our MF field, as you and I and others have discussed, there are a couple of things to keep your eye on. One is the development of JAK inhibitors plus another drug, which we'll talk about. These are combinations that build on the JAK inhibitor backbone. We've had several of these combinations make it all the way to phase 3 randomized frontline trials, and there are some mixed results that we can talk about. This is a novel agent plus a JAK inhibitor. And then lastly, the development of improving anemia in MF. I'm happy to see some movement there. Again, there are drugs that may either modify the natural history of MF, therefore improving the anemia, or go after the anemia alone. I think those are some categories that are getting all of us excited in the current era. Jain: I think you highlighted the major therapeutic advances that are happening. For all these drugs in development, if you had your clinician hat on, how would you see these being used in the future? Where do you see the field evolving, for example, in the next 10-15 years? Pemmaraju: What a great question, and I think it's going to define a lot of what we do over the next decade. First, I would say that stem cell transplant remains the only curative modality for MPNs in 2025. And I want to repeat that because it is something that you and others have nicely shown us and pioneered. Stem cell and allogeneic transplant remain the only curative modality. I envision that we have an era where we still have stem cell transplant, but perhaps we're able to guide the patients earlier and quicker to transplant, or potentially delay for the ones for whom it may not be as effective. For example, say you have a high-risk, young MF patient — say, a 35-year-old patient with high-risk molecular mutations. We're not curing them with these drugs alone. One hypothesis that I would put forward, and this is a futuristic platform: Could it be over the next 5-10 years, could we identify that super young but high-risk patient who's fit enough to take, let's say, combination therapy, so a JAK inhibitor plus your best novel agent? And if I can borrow from the terminology of multiple myeloma or acute myeloid leukemia (AML), perhaps an induction, if you will, over X amount of time, using your two best agents upfront, debulk the disease and get it to its best response. And then from there, a branch point — allogenic stem cell transplant, which of course has to be effective and decrease morbidity/mortality — or if unable to go for transplant, then branch point two is more of a consolidation, maintenance approach. Perhaps after you do, I don't know, 3-6 months, then you get down to a single agent rather than doing a sequence. Let's see how it goes. And then by the time transplant comes around, you're neither too healthy nor too sick. So, I put that in one paradigm for the high-risk patient. We can sense that that person's going to go to AML in a few years. Then I would say another bucket is for the patient with PV. For example, we've always said, oh, there's a low-risk PV patient who maybe doesn't need treatment. But then, my goodness, you have the 41-year-old who has a stroke or a heart attack. Maybe it's that we haven't had good enough treatments for those patients, and so you can have a series of drugs, whether it's the interferon agents, JAK inhibitors, or the hepcidin mimetic modulators, that can be given either as a single agent or — I know this is going to be paradigm-shifting — as a combination, a hepcidin mimetic plus something else, and, again, modify the disease to the point where you don't ever have that first thrombotic event. That's what I'm envisioning. We're not there yet, necessarily, mainly because of financial toxicity, medical complications and drug toxicity. But I wanted to put those kinds of cutting-edge concepts to you. What do you think, Dr Jain? Jain: That sounds phenomenal. I love that approach: thrombosis-free in an early MPN. I guess if I can repeat some of your words, optimizing patients on their way to a transplant, because all of us have shown that the better the disease control going into transplant, the better the outcome. When patients are truly high risk and transplant is sort of inevitable, can we optimize disease outcomes better from a spleen standpoint, or in general health status, performance status standpoint, or even marrow fibrosis, which we've never looked into in much detail? Can transplant outcomes be better? And the ones who are not high risk and don't need a transplant, or a transplant may not be as necessary right away, can we stall this or stall the disease progression further? Certainly, data with interferons are now starting to guide us a little bit in that scope as well. I think a lot of credit goes to the improved diagnostics and vital applicability of next-generation sequencing panels and such. I'm sure you feel the same way, but every time we see that young patient with a splanchnic vein thrombosis and the liver consequences as a result, it breaks your heart. This is why I do not like that terminology, "low risk," because no diagnosis is low risk. I think focusing on the thrombosis component, where the efforts tend to be less focused when the disease seems low risk, would be a dream come true, right? Like we have a thrombosis-free situation from JAK2, sort of delving a little more into that, in terms of diagnostics. Where do you think the untapped areas are? Pemmaraju: I love this question. We don't talk about it enough at our meetings, and it's only a platform like this where you're given an opportunity. If we can be current, modern, and futuristic, I can identify three areas that are on my mind right now. I love what you said about next-generation sequencing. Of course, for you and me it is so common, so mandatory, but we know that not every institution has done that. We advocate for people to check beyond the big three: JAK2, MYC1 , and CALR . So please do check TP53 s and ASXL1 . A lot of these mutations are part of the modern scoring systems for high-risk transplant and may even determine clinical trial eligibility. One area that is starting to pop up — we're using it here at MD Anderson, and I think we'll catch on in the next few years — is something called OGM, optical genome mapping. It sounds futuristic and costly, and it sort of is both of those right now. It's a way to look beyond cytogenetics and the molecular level. We are already in the first year or two of implementation, seeing novel or at least cryptic fusions and other entities that we never picked up before. This is also a way to pick up known entities that are a little bit harder to find, like 8p11 syndrome, where you have an approved drug that you can give. So, I think it is a deeper and more elegant method of finding these molecular and chromosomal abnormalities beyond what we have. They always start as costly and inaccessible, and then over time become more accessible. That's one approach. Another approach is the work of Daniel Royston and Adam Mead. When they first started talking about this, my goodness, it was futuristic, but it is the development of AI and math modeling to take previously invasive methods of diagnosis and make them noninvasive. The easiest way that they've explained it to me, and the way I can explain it to folks, is starting with some of the information we get from bone marrow fibrosis, which you had mentioned earlier. This is phenomenal. Can we get to the point where, without having to use a needle or a bone marrow biopsy, we can somehow monitor what's going on in the patient's system deeper than the blood and the blood smear? That would be 3D, math, modeling, and AI. And of course, in the past year or two, AI is so well developed compared to just 5 years ago. The use of AI in our diagnostics, I predict, is not a hundred years away. I think it's much, much sooner than that. And then the last thing I would say in diagnostics, that I have seen help us tremendously, is the advent of the bone marrow biopsy itself, checking the flow cytometry and other adjunct tests rather than doing them at different time points. On the bone marrow, if you can pull multiple pulls, as you said, so next-generation sequencing, I would rate it highest; but cytogenetics, flow cytometry, and even this OGM could be done. So, multiple pulls on the same bone marrow biopsy. And then, obviously, pathologist reading is still important for morphology — for example, prefibrotic MF vs ET and MF. I would say, improve methods at the level of the hematopathologist. Of course, that comes from expert training, interacting with us as clinicians. Those are some of the things I see that would help, and I think it has not just academic implications. I would say the advent of the prefibrotic MF is something where, in the past 5, 10 years, you can identify a subset of patients that may be a bit different from ET, not quite to MF. The advent of checking ASXL1, TP53 , and early watching for dynamic clonal evolution, including it in your MIPSS70 score, who's going to go to transplant earlier? And then remember selecting clinical trials if, unfortunately, a patient has relapsed or refractory disease. We found a FLT3 mutation or an IDH mutation that may have an approved drug from somewhere else. These are some of the applications I think are helping. Jain: That makes a lot of sense. I'd love to continue to hear about the OGM platform. As we always say, genomics is driving much of this, obviously with some external second impact as well. But genomics is a big point — not just in diagnostics but also in therapeutic implications and progression, and all the decisions that we make around that. You and others have done a lot of work in therapeutic development in MF. I hope I'm wrong, but I always feel that MF tends to remain this rare blood malignancy, and everything reaches us last, right? Like it's the wicked stepchild of heme malignancies. In terms of therapeutics, we've seen targeted agents develop in AML and other malignancies. We've seen that venetoclax may be finding some space in advanced MF or at least being anecdotally used, or more than anecdotally used. We've seen cellular therapy being developed in some of the other heme malignancies. What are your thoughts on the therapeutic development, outside of the drugs that are in the pipeline right now? Pemmaraju: This is a passion area for me. I think this is so important that we can't discuss it enough. Broad strokes first. It is surprising to me — that's the word I would use — that we still have a monotherapy-based system as the backbone, particularly for these advanced patients with MF. It's very surprising to me. It's not because you, I, Ruben [Mesa], and others haven't tried. We've tried. The problem has been with some of the early efforts, BCL-XL inhibition and bromodomain inhibition in particular. But we made it all the way to phase 3, positive primary data, which means spleen volume reduction was met. Double that of ruxolitinib or JAK inhibitors alone. But we, importantly, did not meet the symptom burden expectation for improvement statistically. So, point number one — and this is controversial, what I'm going to say, so I want to say that not everyone will agree with me, but I'm wondering out loud — can we move beyond spleen and symptoms? As we move beyond JAK inhibitor monotherapy, where that system was developed, and either add, incorporate, or yes, potentially even replace with overall survival, progression-free survival, event-free survival, as our colleagues in AML and multiple myeloma, and others have done. This, I think, is a central concept, and I'll advocate that every day. Two, there are new, even more novel agents that are coming in: PIM kinase, telomerase inhibition, XPO1, MDM2. All of these are actually in phase 2 to phase 3 testing, as a novel agent by itself after JAK inhibitors, so, sequential or in combination with the JAK inhibitor. I think it's important to include some of the mechanisms of action. Can we start to see cytokine improvement? Can you start to see biochemical evidence that the agent is working for its target? What about marrow fibrosis reversal, as you nicely said in the earlier segment? I wonder if we can have spleen and symptoms, fine. That is our backbone. But we also need to build in other outcomes — overall survival (OS), progression-free survival (PFS), event-free survival (EFS) — and the ability to bridge patients to transplant. Those are very important, successful markers of whether the drug is working. And then a third layer, biochemical correlates. These are not random. I'm not saying a random wish list, but personalized to each drug. And then Roman numeral two is allele clearance. We used to say that we're never going to see that. Well, guess what? Claire Harrison in the JCO MAJIC study, a study that you and I know well, showed for the very first time that ruxolitinib in advanced PV — not MF but PV — not only cleared the allele burden but also correlated finally with OS and EFS. And EFS includes thrombosis-free interval — all of these important endpoints. In MF, we're starting to try to correlate these things, and we need to show that. And finally, another area is the bridge to stem cell transplant. That's a huge success in this field if you're not curing the disease, which we have not yet, with single agents or with double agents, for that matter. As we were discussing earlier, can you at least get someone into a best response? And then because you can do that bridge to transplant, that should be a success, not a failure, that you "came off the study." What I'm calling for here, to say it directly, is that as a field, we need to follow patients for the long term. We need to follow patients not just for 24 weeks but for 5, 7 years. We need to look at transplant as a part of the journey, not an end. Now, you come off the study and, oh, we don't know what happened after that. And so the length of these studies, I think, has been a big failure really for our field. We know the realistic reason. It costs lots of money, resources, time, and effort from both the patients and the providers. But if we can commit to that, have realistic correlatives and realistic endpoints, I think we could see a huge boon in drug development. Jain: That's a phenomenal point. As you said this, I was thinking about how posttransplant monitoring would mostly be clinical outcomes monitoring, and I wonder if this is sort of an opportunity to partner with the Center for International Blood and Marrow Transplant Research (CIBMTR). Pemmaraju: Wow. Yes. Jain: Perhaps this is something that companies or investigators can partner with to get a more long-term picture of what's happening with these patients. Because it could be either way, right? It could be that these drugs are optimizing patients better for transplant, and the transplant outcomes are better. We don't know that because we're not looking at that. Or maybe there are drugs, God forbid, that are potentially detrimental to the outcome of the transplant. I think that's an important piece to be aware of as well, if that is happening at all. Pemmaraju: To add to that, Dr Jain, I would point the viewers to a couple of different studies in that realm. You've published on exactly what we just said: transplant outcomes. You've also shown immunotherapy as a new area of something to talk about. And then Dr Nico Gagelmann, our colleague, in The New England Journal of Medicine , perhaps just 6 months ago, wrote exactly what we're talking about. So, mutational, clearance, post-transplant. These are the first efforts, your efforts and his, and maybe several others in the field — sort of pre- and posttransplant monitoring and maintenance. I just love what you said, so I want to put that out there. That's an essential thing moving forward. Jain: I think Dr Gagelmann's work, and their team's work, Dr Kroger's and Dr Gagelmann, has certainly helped advance the field. You brought up immunotherapies. I can't let you get away with just mentioning that. I'm going to have you maybe just spend a minute or two on where you think the future of immunotherapy lies. We have CALR -directed antibodies and bispecific T-cell engagers (BiTEs) and JAK2 -directed antibodies, sort of nontransplant immunotherapeutic options. Do you think they'll have a role in the MPN space? Pemmaraju: Oh, that's great. I'm going to comment on those, but then I'm going to turn it back to you because you've given a phenomenal talk that I've seen now a couple of times on some of these novel immunotherapeutic agents. But for the ones you asked about, the ones I'm involved in, I'm pretty excited about them. I think that the central tenet that I did not realize a few years ago — correct me if I'm wrong — but since CALR , yes, it hangs out in the nucleus, but when it becomes mutated, it presents to the surface, therefore becoming susceptible to immune attack. That's changed our whole field. Version 1.0 was vaccines. So far, not yet a whole lot of clinical success. Let's see where that field goes. Version 2.0, monoclonal antibodies and bispecifics. That's one we're a part of. Several of our sponsors, whom we've worked with for the more traditional tyrosine kinase inhibitors, have now moved into this field. Those phase 1's are ongoing and enrolling, so we hope to see data from them perhaps as early as the fall or winter in the conferences next year. I think what's interesting there with CALR is you can attack it in any of the immune ways. So, vaccine, monoclonal antibody bispecific, even now, CAR T cells are being developed by our colleagues in Europe — Alexandros Rampotas and Bethan Psaila et al. That's really phenomenally exciting. But what's exciting is how quickly and rapidly we've moved from the preclinical observation to the clinical. In the absence of clinical data, yes, I'm excited about the concept. Let's meet back in 6-12 months and see how it's going. JAK2 , though, even though not directly immune susceptible, at least now we have ways of targeting the mutant clone itself rather than the pathway. There are the first two different drugs, either is mutant selective or mutant specific. But I've got to turn it back to you. You've given some nice updates on immunotherapeutics in the myeloid neoplasm, so I'd love to hear your update. You've got some cutting-edge ones. Jain: I think you summarized it beautifully. Obviously, I'm biased around this, but I do think immunotherapy has been transforming in general in the oncologic space. It's just taken some time to get to MF, as you beautifully alluded to. There is a challenge with the targets. You may or may not know this, but the fact that the CALR is the most immunogenic is something that Ruben Mesa and I worked with Peter Cohen, MD, on at Mayo Clinic, Arizona, back when I was a fellow. That project, like many other fellow projects, did not come to fruition. So, it's not a published project, but we had some funding around it, and we collected a bunch of CALR patient samples to work on some of the peptide sequencing in Dr Cohen's lab. This is something that's been of interest for a while, and it has been a joy to watch some of the novel ways to target CALR now being developed. I suspect we'll hear more at the European Hematology Association annual meeting and some of the other meetings. I don't know how much I can say right now, but we'll hear at some of the upcoming meetings what the data look like and where the promise of these will be, in general. As you've mentioned, we've blocked pathways so far, and we've seen some suppression of disease or myelosuppression in cytoreduction. We haven't quite seen getting rid of the mutant clone, which is what is needed, with or without a transplant. I would hope that these drugs can potentially get us there. Maybe not in version 1.0, as you mentioned, but maybe in version 6.0 or 3.0. We'll see, but I think at least it's getting there. At least we're thinking about it and investing time and money into it. This has been such an enlightening discussion. Maybe if we could close this by hearing: What is Dr Naveen Pemmaraju's dream treatment paradigm for MF? Pemmaraju: Wow, this has been fantastic. You promised me that we'd be talking about futuristic things. The disclaimer here is, yeah, this is going to be some futuristic, cutting-edge stuff I'm going to say. But let's put it out there. When we were talking earlier, it stimulated something that I want to say, which is: Can we hit this awful disease earlier before it's too late? You nicely said that because you also are one of the experts in our field who knows both MPN and transplant, and oftentimes we're sending our patients too late to transplant, when the disease is too advanced or when the body is too sick. I would say there are two areas I didn't mention. One is CHIP. CHIP is clonal hematopoiesis of indeterminate potential. We've known about CHIP for a decade or so, I want to put out there that JAK2 is among the top five most common mutations found in CHIP. My suspicion, at least, is we've started to see that some of those JAK2 CHIPs could either transform to MPN or maybe they already are a low-grade MPN, because these patients have thrombotic events and cardiovascular events. I don't know if the term is "chemoprevention" or "early identification," but we're seeing CHIP clinics, at your institution and mine, Sloan Kettering, all around the world, starting to develop. But what I'd like to challenge the stakeholders, pharma, philanthropy, investigators — everybody — to is the question: Can we start to develop actual targeted therapy at the level of CHIP, at least for JAK2 CHIP? I'm only talking about our MPN field, before it turns into MPN. That is one thing that could be a decade-long effort. Number two, as we mentioned, you said it beautifully, is, I don't like the moniker of "low risk" because low risk means we don't have treatments yet to use, and the risk-benefit balance isn't there. We want to double down. The PV field is a good one for testing. The hepcidin mimetics modulators work that I've been part of; we're going to hear more about them in the summer and fall meetings. By themselves, they may not eradicate the disease clone. They weren't designed to do that. But perhaps they can make people phlebotomy-free. But either of those, in combination with other agents; or can we give them as solo agents to patients previously thought of as low risk? Make someone phlebotomy-free? We need to show this over time; then they can be thrombosis-free, cardiovascular event-free. My thoughts on the earlier disease and then in MF, as we both said: Can we get to the point where it's okay to treat the disease earlier, upfront, and attack it before the clones have a chance to escape? Could it be a combination therapy upfront, then followed by a more long-term consolidation maintenance? I'd like to see transplant moved up earlier and more often, with all the great developments that are happening post-transplant with better supportive care. And then for that large chunk of patients who are truly, truly stem cell transplant ineligible, can we do what you said earlier, which is to give them a phenomenal therapy with minimal side effects? Because at the end of the day, our friend, mentor, and colleague, Ruben Mesa, says it best, which is, can we have our patients live longer and live better? That's my dream paradigm and I think we are getting there. I think we're going to see a lot of developments in just the next 3-5 years. Jain: What I'm hearing you say repeatedly is overall survival. Pemmaraju: Yes. You heard that right. Jain: We want agents that will help us achieve that. Not just overall survival, I guess, but improved quality of life. Better overall survival, better quality of life. Well, Dr Pemmaraju, this has been a fun discussion, and the evidence of that is that this is the longest podcast that we have recorded so far. I could keep going and hearing from you about all the wonderful things. It has been fun, and I hope our audience has enjoyed it as well. We heard about some of the early-stage developments that Dr Pemmaraju summarized, with hepcidin mimetics, LSD1 inhibitors, and then in MF, combinations, and how to use them, maybe as an initial induction and staying on a less aggressive treatment as maintenance. I'm ever so grateful to Dr Pemmaraju for giving a shout-out to the role of transplant as well. Although I will say that if immunotherapy does the job, I'm happy to open my coffee shop and not transplant. If there are better treatments, that is what we want. Ultimately, we'll be excited to hear about how your work with the OGM goes, the optical genome mapping. That sounds fantastic. And we talked about strategies to improve fibrosis, which we hear less about but are certainly important. There's so much to summarize, Dr Pemmaraju, and I'm so thankful to you for bringing all of these things up and sharing your vision for the future today. Pemmaraju: Thank you so much, Dr Jain, for having me. This was phenomenal. Listen to additional seasons of this podcast. Manipulating Hepcidin in Polycythemia Vera Role of ASXL1 and TP53 Mutations in the Molecular Classification and Prognosis of Acute Myeloid Leukemias With Myelodysplasia-Related Changes Cryptic KMT2A::AFDN Fusion Due to AFDN Insertion Into KMT2A in a Patient With Acute Monoblastic Leukemia 8p11 Myeloproliferative Syndrome: A Review What's Next? Clinical Trials in Myelofibrosis Artificial Intelligence-Based Morphological Fingerprinting of Megakaryocytes: A New Tool for Assessing Disease in MPN Patients Phase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies The Telomerase Inhibitor Imetelstat Differentially Targets JAK2V617F Versus CALR Mutant Myeloproliferative Neoplasm Cells and Inhibits JAK-STAT Signaling A Novel Application of XPO1 Inhibition for the Treatment of Myelofibrosis BOREAS: A Global, Phase III Study of the MDM2 Inhibitor Navtemadlin (KRT-232) in Relapsed/Refractory Myelofibrosis Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial Center for International Blood & Marrow Transplant Research (CIBMTR) Donor Types and Outcomes of Transplantation in Myelofibrosis: A CIBMTR Study Clearance of Driver Mutations After Transplantation for Myelofibrosis Development of a First-in-Class CAR-T Therapy Against Calreticulin-Mutant Neoplasms and Evaluation in the Relevant Human Tissue Environment
Yahoo
09-07-2025
- Health
- Yahoo
New Clinical Findings Published in Scientific Journal Nature Validate LIXTE's Ongoing Ovarian and Colorectal Cancer Trials
PASADENA, Calif., July 09, 2025 (GLOBE NEWSWIRE) -- LIXTE Biotechnology Holdings, Inc. ('LIXTE' or the 'Company') (Nasdaq: LIXT and LIXTW), a clinical stage pharmaceutical company, today announced that the medical journal Nature has published findings by a team of physician-scientists that validate LIXTE's ongoing clinical trials with its proprietary compound LB100 for Ovarian and Colorectal cancers ( A team led by principal investigator Amir Jazaeri, MD, professor of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center, studied survival outcomes of Ovarian Clear Cell Carcinoma (OCCC) patients treated with immune checkpoint blockade therapy ( identifier: NCT03026062). The ;study showed that patients having tumors with inactivating mutations in PPP2R1A - the major scaffold subunit of protein phosphatase 2A (PP2A) - had significantly better overall survival, compared with patients who did not have this mutation in their tumors. Inactivating mutations in PPP2R1A are known to reduce the enzymatic activity of PP2A, which is the target of LIXTE's lead compound LB-100. Tumors with mutations in PPP2R1A were found to have increased the interferon gamma response pathway, which is known to be associated with improved immune checkpoint responses. LIXTE is currently investigating the activity of LB-100 in combination with checkpoint immunotherapy in two clinical trials. The first is enrolling patients with OCCC, led by Dr. Jazaeri at MD Anderson Cancer Center, and also is open at Northwester University. In this trial, LIXTE is collaborating with GSK to test LB-100 in combination with dostarlimab (anti PD1). In the second trial, at the Netherlands Cancer Institute, LIXTE is collaborating with Roche to test LB-100 in combination with atezolizumab (anti PDL1) in colon cancer patients. 'Not only did we identify a new biomarker for improved survival with immunotherapy in ovarian cancer, but we also confirmed the correlation of this biomarker with survival benefit in other cancer types,' said Dr. Jazaeri, who was co-senior author of the Nature article. 'Since PPP2R1A mutations are relatively uncommon, we believe the same benefits may be possible by targeting the PPP2A pathway using drugs, which we currently are evaluating in a clinical trial at MD Anderson.' Bas van der Baan, LIXTE's Chief Scientific Officer, added, 'This work extends a body of pre-clinical evidence indicating that LB-100 is strongly synergistic with checkpoint immunotherapy in a range of cancer types. We look forward to the first results of our clinical studies in the second half of this year.' About LIXTE Biotechnology Holdings, Inc. LIXTE Biotechnology Holdings, Inc. is a clinical-stage pharmaceutical company focused on new targets for cancer drug development and developing and commercializing cancer therapies. LIXTE has demonstrated that its first-in-class lead clinical PP2A inhibitor, LB-100, is well-tolerated in cancer patients at doses associated with anti-cancer activity. Based on extensive published preclinical data (see LB-100 has the potential to significantly enhance chemotherapies and immunotherapies and improve outcomes for patients with cancer. LIXTE's lead compound, LB-100, is part of a pioneering effort in an entirely new field of cancer biology – activation lethality – that is advancing a new treatment paradigm. LIXTE's new approach is covered by a comprehensive patent portfolio. Proof-of-concept clinical trials are currently in progress for Ovarian Clear Cell Carcinoma, Metastatic Colon Cancer and Advanced Soft Tissue Sarcoma. Additional information about LIXTE can be found at Forward-Looking Statement Disclaimer This announcement contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, and Section 21E of the Securities Exchange Act of 1934. For example, statements regarding the Company's financial position, business strategy and other plans and objectives for future operations, and assumptions and predictions about future activities, including the continuing development of proprietary compounds, the planning, funding, coordination and potential results of clinical trials, the patent and legal costs to protect and maintain the Company's intellectual property worldwide, and the Company's ability to obtain and maintain compliance with Nasdaq's continued listing requirements, are all forward-looking statements. These statements are generally accompanied by words such as "intend," anticipate," "believe," "estimate," "potential(ly)," "continue," "forecast," "predict," "plan," "may," "will," "could," "would," "should," "expect" or the negative of such terms or other comparable terminology. The Company believes that the assumptions and expectations reflected in such forward-looking statements are reasonable, based on information available to it on the date hereof, but the Company cannot provide assurances that these assumptions and expectations will prove to have been correct or that the Company will take any action that the Company may presently be planning. However, these forward-looking statements are inherently subject to known and unknown risks and uncertainties. Actual results or experience may differ materially from those expected or anticipated in the forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, regulatory policies, available cash resources, research results, competition from other similar businesses, and market and general economic factors. Readers are urged to read the risk factors set forth in the Company's filings with the United States Securities and Exchange Commission at The Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. For more information about LIXTE, Contact: For more information about LIXTE, Contact: info@ General Phone: (631) 830-7092; Investor Phone: (888) 289-5533orPondelWilkinson Inc. 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Medscape
09-07-2025
- Health
- Medscape
Drug Combo Outpaces Standard Chemo in R/R LBCL
A combo of the novel bispecific antibody mosunetuzumab and the antibody-drug conjugate polatuzumab vedotin (Mosun-Pola) significantly outperformed standard chemotherapy in transplant-ineligible patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), an industry-funded phase 3 trial found. Over a median 23.2 months follow-up, progression-free survival in patients with R/R LBCL was a median of 11.5 months for Mosun-Pola vs 3.8 months for the rituximab-gemcitabine-oxaliplatin (R-GemOx) regimen (hazard ratio [HR], 0.41, P < .0001), reported lead author Jason Westin, MD, MS, professor, Department of Lymphoma & Myeloma, MD Anderson Cancer Center, Houston, at the annual International Conference on Malignant Lymphoma (ICML) meeting in Lugano, Switzerland. The other primary endpoint, objective response rate, was higher in the Mosun-Pola group than the R-GemOx group (70.3% vs 40.0%; P < .0001). The data from the SUNMO trial 'demonstrate the potential of Mosun-Pola as a well-tolerated combination that can be delivered in the outpatient setting for a fixed duration and prolong remission for people with R/R LBCL,' said Westin in an interview. As Westin noted, about 40% of newly diagnosed patients with LBCL don't respond to rituximab-based immunochemotherapy or relapse after treatment. More than half of the patients with R/R LBCL, he said, are not eligible for two second-line treatments — chimeric antigen receptor (CAR) T-cell therapy and high-dose chemotherapy with autologous stem-cell transplantation. While there are other options, 'many patients lack access to highly effective therapies due to logistical and toxicity-related concerns,' Westin said. A New Combo Gets Tested Enter Mosun-Pola, which combines mosunetuzumab (Lunsumio), which is FDA-approved for patients with R/R follicular lymphoma after two or more lines of therapy, and polatuzumab vedotin (Polivy), which is FDA-approved for both newly diagnosed and R/R LBCL with conventional chemotherapy. 'Mosunetuzumab and polatuzumab vedotin have different mechanisms of action,' Westin said. 'By combining these medicines, we hoped to build upon the success of these drugs when used alone and improve outcomes.' For the study, researchers randomly assigned 138 patients to Mosun-Pola (8 cycles every 21 days) and 70 to R-GemOx (eight cycles every 14 days). Among all patients, 43.8% had received one prior therapy, and 73.6% had primary refractory disease or relapse < 12 months from first-line therapy. The study population had a median age of 62-63 years, and the oldest patient was 87. The complete response rate was 51.4% for Mosun-Pola and 24.3% for R-GemOx. After 1 year, 72.6% of patients with complete response were still in remission (95% CI, 61.4-83.8) vs 44.1% 95% CI, 13.2-74.9), respectively. Safety Evaluation Favors Mosun-Pola Interim overall survival favored Mosun-Pola (median, 18.7 months; 95% CI, 14.1-not evaluable, vs 13.6 months; 95% CI, 9.9-not evaluable, respectively; HR, 0.80; 95% CI, 0.54-1.20). Among 135 Mosun-Pola- and 64 R-GemOx-treated patients evaluated for safety, rates of grades 3-4 events were similar in the groups (58.5% vs 57.9%, respectively) as were grade 5 events (5.2% vs 6.3%, respectively). Rates of thrombocytopenia (8.9% vs 65.6%, respectively) and peripheral neuropathy (24.4% vs 42.2%, respectively) were much lower in the Mosun-Pola group. In his presentation at the ICML meeting, Westin said any grade of cytokine release syndrome (CRS) was seen in 25.9% of patients. 'However, grade 2 or above was observed in only 4.4% of patients, and grade 1, which is a fever only, was observed in 21.5% of patients. This means that of the patients treated with Mosun-Pola, 96% did not have any significant CRS.' No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were seen in the Mosun-Pola group. Outside Specialist Is Not Wildly Impressed In an interview, Stephen D. Smith, MD, associate professor at the University of Washington and medical oncologist at the Fred Hutchinson Cancer Center, Seattle, who was not involved in the SUNMO trial, noted that the current treatment landscape is complex. 'This is a crowded field, and the added value of this study is modest,' he said. 'The comparator R-GemOx is a niche regimen — mainly used for bridging to CAR-T or even palliative therapy in the US. Other options are approved in this space, so beating R-GemOx in progression-free survival is only a small part of a complex picture.' Smith pointed out that several competing therapies already exist in this space. 'We already have FDA approvals for epcoritamab and glofitamab in the third-line space, and these same drugs hold promise — though are not approved — when combined with R-GemOx in second line or later DLBCL treatment,' he said. Two other options are loncastuximab and tafasitamab with lenalidomide, he said. Still, Mosun-Pola 'Dunked' on R-GemOx Regarding the study's design, Smith noted that it includes transplant-ineligible patients, which is not the same as CAR T-cell therapy-ineligible. 'CAR T-cell therapies are the main priority for high-risk, early relapsed DLBCL, and for third-line patients.' Still, he said that Mosun-Pola 'dunked on R-GemOx' in terms of progression-free survival, and 'from anecdotal experience, patients feel reasonably good on these therapies, especially after getting through the first cycle and if they can dodge infections.' When asked for a response, Westin noted that the positive outcomes in efficacy were achieved with the favorable toxicity profile. The lowest rate of CRS of any T-cell directed therapy to date is an important differentiating factor which could allow usage at more centers than currently use bispecific antibodies. Also, he said, 'Mosun-Pola does not include conventional chemotherapy, a first for a positive phase 3 trial in this space.' As for the role of R-GemOx, he said 'this is a commonly accepted treatment in the United States and globally for patients who are not intended for transplant. It's both listed in guidelines worldwide and is the control arm for at least five studies in this space.' Next Up: Submission to FDA What now? Genentech plans to submit the study findings to regulatory agencies such as the FDA, and it notes that the National Comprehensive Cancer Network has added Mosun-Pola as a recommendation for the treatment of people with second-line DLBCL who are not headed to transplant. However, Smith said he doesn't expect the study findings 'will change standard of care, which is rapidly evolving with several options all of which are likely — or proven to be — better than R-GemOx,' Smith said. As for cost, Westin declined to discuss the potential price of a Mosun-Pola product. Smith said it would be extremely expensive.
Yahoo
07-07-2025
- Business
- Yahoo
SELLAS Life Sciences Appoints Linghua Wang, MD, PhD, to Scientific Advisory Board
NEW YORK, July 07, 2025 (GLOBE NEWSWIRE) -- SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ('SELLAS'' or the 'Company'), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, today announced the addition of Linghua Wang, MD, PhD, to its Scientific Advisory Board (SAB). Dr. Wang is a widely respected leader in cancer research and translational science, and she joins the Company's SAB shortly after the appointments of Philip C. Amrein, MD, and Dr. Alex Kentsis, MD, PhD. 'We are thrilled to welcome Dr. Wang to our Scientific Advisory Board,' said Dragan Cicic, MD, Senior Vice President, Chief Development Officer of SELLAS. 'Her decades of experience in cancer immunogenomics and computational biology are directly aligned with our focus on translational research, artificial intelligence utilization around genomics, proteomics as well as transcriptomics, and precision medicine. With the recent additions of Drs. Amrein and Kentsis, we are building a uniquely experienced and visionary team that will help guide our scientific and clinical strategy during this critical phase of growth. Their collective insights will be invaluable as we approach key clinical milestones expected for both of our assets later this year.' Dr. Wang is a tenured Associate Professor in the Department of Genomic Medicine at MD Anderson, where she leads the Computational Biology Laboratory. She also holds a dual appointment as an Associate Member of The James P. Allison Institute, serves as Co-Lead of Focus Area 2 (Single-Cell Analytics & Spatial Multi-Omics) at the Institute for Data Science in Oncology, and is a faculty member in the Quantitative Sciences and Immunology PhD Programs at the UTHealth Houston Graduate School of Biomedical Sciences. Trained in Clinical Medicine, she earned her PhD in Cancer Genomics from the University of Tokyo and completed postdoctoral training at Baylor College of Medicine, where she was subsequently promoted to faculty. She was recruited to MD Anderson Cancer Center in 2017. Her research focuses on unraveling complex tumor ecosystems, with an emphasis on understanding cellular and molecular heterogeneity and dynamics, phenotypic plasticity, and interactions between cancer cells and the tumor microenvironment that drive disease progression and therapy response. Her group leverages cutting-edge single-cell and spatial omics, molecular imaging, AI-driven pathology, and advanced bioinformatics and machine learning approaches to enable transformative discoveries. Dr. Wang's work aims to advance predictive and precision oncology by developing robust models of patient response and uncovering novel therapeutic targets, with the ultimate goal of transforming how cancers and their precursors are detected, classified, and treated. She holds multiple NIH/NCI funded grants, has published over 100 articles in high-impact journals, and is an internationally recognized leader in cancer research. Her work is highly collaborative, spanning national and international partnerships to advance cancer understanding and treatment. About SELLAS Life Sciences Group, Inc. SELLAS is a late-stage clinical biopharmaceutical company focused on the development of novel therapeutics for a broad range of cancer indications. SELLAS' lead product candidate, GPS, is licensed from Memorial Sloan Kettering Cancer Center and targets the WT1 protein, which is present in an array of tumor types. GPS has the potential as a monotherapy and combination with other therapies to address a broad spectrum of hematologic malignancies and solid tumor indications. The Company is also developing SLS009 (tambiciclib) - potentially the first and best-in-class differentiated small molecule CDK9 inhibitor with reduced toxicity and increased potency compared to other CDK9 inhibitors. Data suggests that SLS009 demonstrated a high response rate in AML patients with unfavorable prognostic factors including ASXL1 mutation, commonly associated with poor prognosis in various myeloid diseases. For more information on SELLAS, please visit Forward-Looking Statements This press release contains forward-looking statements. All statements other than statements of historical facts are 'forward-looking statements,' including those relating to future events. In some cases, forward-looking statements can be identified by terminology such as 'plan,' 'expect,' 'anticipate,' 'may,' 'might,' 'will,' 'should,' 'project,' 'believe,' 'estimate,' 'predict,' 'potential,' 'intend,' or 'continue' and other words or terms of similar meaning. These statements include, without limitation, statements related to the GPS clinical development program, including the REGAL study and the timing of future milestones related thereto. These forward-looking statements are based on current plans, objectives, estimates, expectations, and intentions, and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties with oncology product development and clinical success thereof, the uncertainty of regulatory approval, and other risks and uncertainties affecting SELLAS and its development programs as set forth under the caption 'Risk Factors' in SELLAS' Annual Report on Form 10-K filed on March 20, 2025 and in its other SEC filings. Other risks and uncertainties of which SELLAS is not currently aware may also affect SELLAS' forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. The forward-looking statements herein are made only as of the date hereof. SELLAS undertakes no obligation to update or supplement any forward-looking statements to reflect actual results, new information, future events, changes in its expectations, or other circumstances that exist after the date as of which the forward-looking statements were made. Dr. Wang receives compensation as a member of SELLAS's Scientific Advisory Board, and this financial relationship has been disclosed to MD Anderson's Conflict of Interest Committee in accordance with institutional policy. Investor Contact John FrauncesManaging DirectorLifeSci Advisors, LLCjfraunces@ in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
Yahoo
01-07-2025
- Business
- Yahoo
Natera to Present Clinical and Economic Utility of Signatera at ESMO GI, Highlights Innovations in MRD
AUSTIN, Texas, July 01, 2025--(BUSINESS WIRE)--Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and precision medicine, announced new data that will be presented at the 2025 European Society for Medical Oncology GI Congress (ESMO GI) in Barcelona, Spain. These presentations reinforce the strong clinical and economic utility of Signatera™ monitoring across colon and rectal cancers (CRC), as well as new clinical validation data on its tissue-free MRD assay. Signatera in CRC surveillance Data on >3,000 CRC patients will be shared in an oral presentation, concluding that adding Signatera ctDNA* monitoring to the current standard of care in surveillance can better identify patients who are candidates for metastasis-directed therapy (MDT). Results indicated that Signatera-positive patients were up to 20x more likely to receive curative-intent MDT than Signatera-negative patients. By comparison, CEA positivity led to only a 2x increase, with no added value in stage IV. Signatera Genome in rectal cancer An analysis will be presented from the MD Anderson INTERCEPT study (n=31) that used serial Signatera Genome testing in patients with locally advanced rectal cancer after neoadjuvant therapy. Results demonstrated 100% specificity/PPV, with surveillance sensitivity of 100% in the surgical cohort and 88% (7/8) overall. Economic utility of Signatera-guided therapy in adjuvant CRC A budget impact model from BUPA, a multinational health insurance provider with over 60 million customers, will outline a 43% expected reduction in healthcare costs using Signatera-guided adjuvant treatment versus standard of care in stage II-III CRC. "We're excited to present these new findings that continue to support the utility of Natera's products across GI cancers," said Adham Jurdi, M.D., senior medical director of oncology at Natera. "These data highlight our commitment to improving outcomes and driving innovation in MRD detection." Full list of data featuring Natera's technology at ESMO GI: July 4, 16:40-16:50 CET | FPN: 20 | Signatera (Oral Presentation)Presenter: Arvind Dasari, M.D., MSClinical utility of including circulating tumor DNA (ctDNA) monitoring in standard of care (SoC) colorectal cancer (CRC) surveillance July 4, 16:50-17:00 CET | FPN: 30 | Signatera (Oral Presentation)Presenter: Hideaki Bando, of ctDNA Clearance with Disease-Free Survival and Safety and Quality of Life from ctDNA-Directed Therapy: Findings from the ALTAIR Study July 4, 15:30-16:30 CET | FPN: 102P | Signatera (Poster Presentation)Presenter: Christos Mikropoulos, MBBS, MSc, M.D. (Res), MRCP, FRCRDirect cost of healthcare analysis of Signatera ctDNA testing in the adjuvant setting for a hypothetical cohort of stage II and stage III colorectal cancer (CRC) patients: a UK private payer perspective July 4, 15:30-16:30 CET | FPN: 243P | Signatera Genome (Poster Presentation)Presenter: Arvind Dasari, M.D., MSClinical performance of Signatera Genome assay in a sub-cohort of locally advanced rectal cancer (LARC) patients (pts) in the MD Anderson INTERCEPT program July 4, 15:30-16:30 CET | FPN: 93P | Tissue-free MRD (Poster Presentation)Presenter: Yoshiaki Nakamura, M.D., validation of a methylation-based, tissue-free colorectal cancer test for the detection of molecular residual disease by circulating tumor DNA July 4, 15:30-16:30 CET | FPN: 89P | Early Cancer Detection (Poster Presentation)Presenter: John P.Y. Shen, of methylation-based biomarkers to predict metastases, treatment effect, and microsatellite status in colorectal cancer Notes*Circulating tumor DNA About Natera Natera™ is a global leader in cell-free DNA and genetic testing, dedicated to oncology, women's health, and organ health. We aim to make personalized genetic testing and diagnostics part of the standard-of-care to protect health and inform earlier, more targeted interventions that help lead to longer, healthier lives. Natera's tests are supported by more than 300 peer-reviewed publications that demonstrate excellent performance. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas, and San Carlos, California. For more information, visit Forward-Looking Statements All statements other than statements of historical facts contained in this press release are forward-looking statements and are not a representation that Natera's plans, estimates, or expectations will be achieved. These forward-looking statements represent Natera's expectations as of the date of this press release, and Natera disclaims any obligation to update the forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to whether the results of clinical or other studies will support the use of our product offerings, the impact of results of such studies, our expectations of the reliability, accuracy and performance of our tests, or of the benefits of our tests and product offerings to patients, providers and payers. Additional risks and uncertainties are discussed in greater detail in "Risk Factors" in Natera's recent filings on Forms 10-K and 10-Q and in other filings Natera makes with the SEC from time to time. These documents are available at and View source version on Contacts Investor Relations: Mike Brophy, CFO, Natera, Inc., investor@ Media: Lesley Bogdanow, VP of Corporate Communications, Natera, Inc., pr@ Sign in to access your portfolio
