Category Archives: Clinical Trial

Karyopharm Receives FDA Fast Track Designation for Selinexor for the Treatment of Myelofibrosis

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– Regulatory Designation Includes Primary Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis and Post-Polycythemia Vera Myelofibrosis –

– Pivotal Phase 3 Study of Selinexor and Ruxolitinib in Treatment-Naïve Myelofibrosis Initiated in June 2023 –

NEWTON, Mass., July 17, 2023 /PRNewswire/ — Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the United States Food and Drug Administration (FDA) has granted Fast Track Designation to the development program of selinexor for the treatment of patients with myelofibrosis, including primary myelofibrosis, post-essential thrombocythemia myelofibrosis, and post-polycythemia vera myelofibrosis.

“Fast Track Designation for selinexor highlights its potential to address the unmet medical need in myelofibrosis, an important acknowledgement as we continue our pivotal Phase 3 study,” said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. “Selinexor’s unique mechanism of action, XPO1 inhibition, is a novel and potentially fundamental mechanism in myelofibrosis. We have been highly encouraged by the efficacy and safety data observed to date [in our Phase 1 study] with selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis and believe selinexor has the potential to shift the treatment paradigm. We look forward to continued interaction with the FDA as we advance the development of this promising treatment for patients in need.”

In June 2023, Karyopharm initiated a pivotal Phase 3 clinical trial (XPORT-MF-034) (NCT04562389) to assess the efficacy and safety of once-weekly selinexor 60 mg in combination with ruxolitinib in JAKi-naïve patients with myelofibrosis. Updated data from the Phase 1 study were presented at the American Association for Cancer Research Annual Meeting 2023, American Society of Clinical Oncology 2023 and European Hematology Association 2023, which showed rapid, deep and sustained spleen responses and robust symptom improvement in patients treated with selinexor 60 mg in combination with ruxolitinib as of the April 10, 2023 cut-off date.  Top-line data from the Phase 3 study is expected in 2025. The Company plans to expand its clinical development program in myelofibrosis by investigating selinexor in other JAKi-naïve settings, such as novel combinations, to benefit the greatest number of patients.

Fast Track Designation is intended to facilitate development and expedite review of drugs to treat serious and life-threatening conditions so that an approved product can reach the market expeditiously. Features of Fast Track Designation include frequent interactions with the FDA review team, and if relevant criteria are met, eligibility for Priority Review and Rolling Review.

Further information about the Phase 3 study can be found at www.clinicaltrials.gov.

About Karyopharm Therapeutics
Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies. Since its founding, Karyopharm has been an industry leader in oral Selective Inhibitor of Nuclear Export (SINE) compound technology, which was developed to address a fundamental mechanism of oncogenesis: nuclear export dysregulation. Karyopharm’s lead SINE compound and first-in-class, oral exportin 1 (XPO1) inhibitor, XPOVIO® (selinexor), is approved in the U.S. and marketed by the Company in three oncology indications and has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including Europe and the United Kingdom (as NEXPOVIO®) and China. Karyopharm has a focused pipeline targeting multiple high unmet need cancer indications, including in multiple myeloma, endometrial cancer, myelodysplastic neoplasms and myelofibrosis. For more information about our people, science and pipeline, please visit www.karyopharm.com, and follow us on Twitter at @Karyopharm and LinkedIn.

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the ability of selinexor to treat patients with myelofibrosis; and expectations related to the clinical development of selinexor and potential regulatory submissions of selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm’s control, that may cause actual events or results to differ materially from Karyopharm’s current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO or that any of Karyopharm’s drug candidates, including selinexor and eltanexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm’s drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm’s drug candidate portfolio will result in stock price appreciation. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm’s drug candidates that receive regulatory approval; the ability to obtain and retain regulatory approval of XPOVIO or any of Karyopharm’s drug candidates that receive regulatory approval; Karyopharm’s results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm’s ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development or regulatory approval of drug candidates by Karyopharm’s competitors for products or product candidates in which Karyopharm is currently commercializing or developing; the direct or indirect impact of the COVID-19 pandemic or any future pandemic on Karyopharm’s business, results of operations and financial condition; and Karyopharm’s ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates. These and other risks are described under the caption “Risk Factors” in Karyopharm’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2023, which was filed with the Securities and Exchange Commission (SEC) on May 4, 2023, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

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EXCEED-ET Investigates an Alternative Option for Disease Modification in Essential Thrombocytopenia

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July 16, 2023

Nichole Tucker

An overperforming JAK-STAT pathway, including the presence of JAK2, CALR, and MPL gene mutations leads to high platelet count in patients with essential thrombocytopenia (ET).1 Safe and potent therapies are needed for these populations, especially for those requiring cytoreduction, regardless of their prior exposure to hydroxyurea and/or anagrelide, according to Lucia Masarova, MD, et al.

There is also an unmet need for treatments that can reduce the risk of thrombohemorrhagic events, ultimately stopping or preventing the development of post-ET myelofibrosis.1

Ropeginterferon alfa-2b-njf (Besremi) is a next-generation interferon alfa agent. It is FDA-approved to treat another myeloproliferative neoplasm (MPN), polycythemia vera (PV). In ET, ropeginterferon alfa-2b-njf is being investigated for the treatment of adult patients in a single-arm, multicenter trial (EXCEED-ET; NCT05482971).

At the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, Masarova, assistant professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, presented the EXCEED-ET study design, noting its potential to fill an unmet need for new therapies to treat adults with ET.

“Eventually, we can hopefully add it to something and maybe keep on some agents that have been around to help control the counts. At the same time, maybe we can do a low-dose interferon for a longer time as a disease modification agent, and hopefully you will wake up in an era where there’s going to be no ET or PV,” Masarova told Targeted OncologyTM, in an interview.

In the interview, Masarova, discussed EXCEED-ET in detail and provided insights into the treatment options for ET and PV.

Targeted Oncology: In terms of disease modification, what is the current state of treatment in MPNs?

Masarova: We hope there will be a goal of therapy in the coming decades. Currently, the therapy goals are kind of focused more in controlling the accounts displaying the symptoms and getting deeper responses. Right now, with some therapies that showed us that we could decrease the allele burden, or we could alter the bone marrow fibrosis, or the bone marrow morphology is going to be the disease modification. As of now, there is no agent that would do it, except for the interferon, which showed quite promisingly that we can bring it into the landscape of the disease.

What does the treatment landscape currently look like for ET?

ET is considered a benign disease. People live with it for a very long time. Currently, treatment is for only those we call high-risk disease patients. Patients that had thrombosis in the past, and then patients that are over the age of 60 years and have a dAkt mutation, and that’s according to the revised International Prognostic Score of Thrombosis for Essential Thrombocytopenia score. Those patients are treated to decrease the risk of thrombosis, but not to do anything else. This is modified just to simply increase the thrombosis risk. That is hydroxyurea, it’s a standard frontline agent, which is an easy to take oral drug. However, it could lead to some resistance or about 30% patients can become.

Because ET also affects younger people, plenty of younger females, they don’t really want to take chemotherapy forever, which I don’t blame them for. They are interested in taking something else. The standard interferon, recombinant or pegylated, which is called the peginterferon alfa-2a [Pegasys]. We’ve recently used this for the couple years has been around for MPNs, particularly for ET and the PV. That is about 40 years almost. This treatment has a lot of data, and a lot of implications. This may be a disease modifying agent, which is an agent that could decrease the allele burden, eradicate the malignant clone, and ultimately change the disease behavior. We were excited. We had novel interferon called ropeginterferon-alpha-2b-njft approved in patients with progressive disease back in 2021. That has been preceded by approval in European Union in 2019. That’s an excellent option in terms of interferons. The normal alternative with the ropeginterferon, which is the novel mono-pegylated form, is kind of more convenient because it’s used every other week. Once we reached complete hematologic control, it’s used once a month. That’s a significant improvement in inconvenience for patients and in tolerability as well as compliance issues. We were excited to get it in PV, and we have it in some studies in PV to expand the access and maybe try a different schedule, and you move it to ET patients. That’s something that we’re going to be looking at.

Then, for patients with PV refractory to hydroxyurea, we have approved sunitinib [Sutent] which is the JAK inhibitor that has solid data in the field after hydroxyurea based on results from the RESPONSE [NCT01243944] and RESPONSE-2 [NCT02038036] trials. It will be 10 years since we had refractory patients treated with ruxolitinib [Jakafi]. It’s an excellent drug for controlling the symptoms and spleen count.

Last year, we had a very excited study called MAGIC-PV [ISRCTN61925716], which was reported by our European colleagues that showed the advantage of ruxolitinib for decreasing the rate of thrombosis hemorrhage. It also actual improved event-free survival, death, and adverse events in terms of progression to myelofibrosis. So, it was exciting. If we consider disease modification is what’s going to be preventing the disease to go into myelofibrosis, I think that will be exciting to see how far we can get in that field.

Can you discuss the rationale of the EXCEED-ET study [NCT05482971]?

The EXCEED-ET study is getting the ropeginterferon, which is the novel interferon into the space of ET. It is phase 1/2 study that gets the ropeginterferon in patients in North America. The patients are hydroxyurea-refractory or hydroxyurea-naive. Patients that have ET platelets over 450,000 need the therapy with some symptoms, and do not have a contraindication for interferons, which also had to be mentioned that the drugs could not be used in patients that have previous autoimmune disease, psychiatric diseases, or neurological because it could aggravate their symptoms. But those patients, if they would be eligible, they could be getting the full access to the drug. Also, with patients with ET, the escalation is going to be a lot faster to 250 micrograms, every other week, 350, and then 500 is the maximum dose that has been explored. However, I have to say the approval of ropeginterferon for PV had even higher dose, and the maximum-tolerated dose was not reached. This is a perfectly safe dose that we have patients on. We’re going to see how it’s going to do in ET patients. There is a core treatment period, which continues after the 4 weeks of escalation of up to 56 weeks. The patients will be dosed every other week with a tolerable dose. We will be monitoring the primary end points of durability of control, hematologic control, platelets less than 450, white cells less than 10. That will basically sustain 80% of 36 consecutive weeks. Then, the key secondary end points are going to include all important end points in ET patients, such as complete hematologic response, composite hematologic response, that includes control of spleen, control of symptoms, absence of disease progression, and absence of thromboembolic events. Then, it’s going to also have this excited end point, which is basically a decline or allele burden. We’ll be checking the allo burden, what we call the molecular response, and then bone marrow morphology response.

Also, there are a couple other exploratory or pharmacokinetic studies that we’re going to be conducting. It’s a study that does not allow patients that were exposed to interferon. For example, patients and [peginterferon alfa-2a] would not be eligible. However, with a plan amendment, there is going to be measurement of neutralizing antibodies against ropeginterferon. If patients are not detected to carry those, they will be still eligible.

If positive, how do you see this study impacting the field?

I’m excited about it. I’ve used interferons in the off-label setting ever since I came to MD Anderson, and it’s been proven to be an effective therapy for young people. I have a lot of patients come in from everywhere and they don’t want to do chemotherapy, they seek the agent. So far, we’ve been only able to give them the [peginterferon alfa-2a], where we have to deal with insurance companies, because it was off-label setting.

Last year, we published 15 years follow-up on our phase 2 study. But this is going to open the use of the agent, I’m excited about the less frequent interactions, which my patients are excited about as well. I’m going to be really comparing and lucky for me, I’ve seen the tolerance of the [peginterferon alfa-2a] in these patients. I will really be comparing them to the ropeginterferon, seeing what this agent could offer, and seeing the results in PV. I’m quite excited about it. I don’t think we will have any data about what we call the disease modification or how we call it in the next 10 years, maybe because it’s a very low progressing disease, but I’m looking forward to seeing whether we’re going to see elimination or absence of disease progression to myelofibrosis. I also wonder if we will see minimization of the thromboembolic events. That will be the ultimate disease modification change.

Afterwards, hopefully we can add it to something and maybe keep patients on some agents that have been around and help control the counts. At the same time, maybe we can do a low dose interferon for a longer time as a disease modification agent, and hopefully you will wake up in an era where there’s going to be no ET or PV.

REFERENCE:

Masarova L, Mascarenhas J, Qin A, et al. EXCEED-ET: A single-arm multicenter study to assess the efficacy, safety, and tolerability of ropeginterferon alfa-2b-njft (P1101) in North American adults with essential thrombocythemia. J Clin Oncol. 2023;41(suppl 16): TPS7088- TPS7088. doi:10.1200/JCO.2023.41.16_suppl.TPS7088

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Pelabresib Combo Improves Spleen/Symptom Burden in JAKi-Naïve Myelofibrosis

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July 9, 2023

Russ Conroy

Combination treatment with pelabresib (CPI-0610) and ruxolitinib (Jakafi) was well tolerated and demonstrated enduring improvements in spleen and symptom burden among patients with JAK inhibitor treatment–naïve patients with myelofibrosis, according to findings from arm 3 of the phase 2 MANIFEST study (NCT02158858).

At week 24, 68% (95% CI, 57%-78%) of patients who received the combination achieved a spleen volume reduction of at least 35% (SVR35), which included a median SVR of –50% (range, –84% to 28%). Additionally, SVR35 responses at 24 weeks were observed in 70% and 67% of patients with intermediate-1– and intermediate-2– or high-risk disease based on Dynamic International Prognostic Scoring System (DIPSS) criteria, respectively, and 82% and 66% of patients based on International Prognostic Scoring System (IPSS) criteria. Kaplan-Meier estimates indicated that 93.5% (95% CI, 87.4%-99.7%) of those with a SVR35 response maintained their response at 36 weeks after onset.

A total symptom score reduction of at least 50% (TSS50) was reported in 56% (95% CI, 45%-67%) of patients at week 24, with a best TSS50 response at any time of 83% and a median change in TSS of –59% (range, –100% to 225%). Additionally, 43% of patients had a TSS50 response at 48 weeks, which included a median change in TSS of –54.8% (range, –100% to 307.1%).

At 24 weeks, study treatment yielded an absolute change in hemoglobin levels from baseline between –1 and at least 1.5 g/dL in 55% of patients; hemoglobin levels improved in 36% of patients, including a mean change of 1.3 g/dL and a median of 0.8 g/dL. Moreover, 24% of patients had a mean hemoglobin increase of at least 1.5 g/dL from baseline over any 12-week period while forgoing red blood cell transfusions.

“To our knowledge, the MANIFEST trial in JAK inhibitor treatment-naïve patients is the first study with a rational combination of BET [inhibitor] pelabresib and ruxolitinib that showed clinically meaningful durable improvements in splenomegaly and symptoms, was associated with biomarker findings indicating potential disease modification, and demonstrated a generally favorable safety profile,” the study authors stated. “This combination has the potential to improve the standard of care for treatment-naïve patients with myelofibrosis and warrants further investigation.”

Investigators of the global, open-label, nonrandomized phase 2 MANIFEST study evaluated pelabresib in combination with ruxolitinib in a cohort of JAK inhibitor treatment-naïve patients with myelofibrosis. Patients received an initial dose of 125 mg of pelabresib once daily for 14 days followed by a 7-day pause in combination with continuous ruxolitinib twice a day. Patients could receive a maximum pelabresib dose of 175 mg once daily.

The study’s primary end point was SVR35 from baseline to 24 weeks measured by imaging. The secondary end point was TSS50, and exploratory end points included bone marrow fibrosis improvement based on blinded central hematopathologist review following European consensus guideline criteria for reticulin fibrosis grading and improvement in anemia and transfusion requirements.

Patients who had not been exposed to treatment with JAK inhibitors and BET inhibitors and had confirmed diagnoses of primary myelofibrosis, or post–essential thrombocythemia or post–polycythemia vera myelofibrosis were eligible for enrollment on the trial. Additional eligibility criteria included having a spleen volume of at least 450 cm3, intermediate-2– or high-risk disease based on DIPSS criteria, and at least 2 measurable symptoms using the Myelofibrosis Symptom Assessment Form v4.0.

Overall, 84 patients received at least 1 dose of the study treatment, 53 of whom remained on treatment at the time of data cutoff. The median patient age was 68 years (range, 37-85), and 70% were male. Additionally, 24% had intermediate-1, 61% had intermediate-2, and 16% had high-risk disease by DIPSS criteria. In terms of mutations, investigators most frequently observed JAK2V617F (74%), ASXL1 (46%), CALR (21%), and MPL (8%).

Blinded central pathology review of bone marrow samples indicated at least 1 grade improvement in reticulin fibrosis at week 24 in 28% of evaluable patients, including 7% who had improvements of 2 grades. Among 24 patients with grade 1 or 2 reticulin fibrosis at baseline, 4 had worsening conditions, including 2 patients each with grade 1 and 2 fibrosis. Investigators observed no significant relationship between reticulin fibrosis improvement and clinical end points in the study,

Overall, 96% of patients experienced at least 1 treatment-emergent adverse effect (TEAE), and 63% had grade 3 or higher TEAEs. The most frequent hematologic TEAEs included thrombocytopenia (52%) and anemia (42%), and the most common nonhematologic TEAEs included diarrhea (35%), fatigue (33%), musculoskeletal pain (30%), respiratory tract infection (29%), and constipation (25%).

Pelabresib dose reductions were necessary among 37% of patients, and 36% had ruxolitinib dose reductions due to TEAEs. There were 5 deaths during study treatment or within 30 days following the final pelabresib dose, including 4 determined to be unrelated to pelabresib treatment. One patient died to multiorgan failure due to sepsis secondary to pneumonia, which investigators deemed to be related to pelabresib.

Reference

Mascarenhas J, Kremyanskaya M, Patriarca A, et al. MANIFEST: pelabresib in combination with ruxolitinib for Janus kinase inhibitor treatment-naïve myelofibrosis. J Clin Oncol. Published online March 7, 2023. doi:10.1200/JCO.22.01972

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Examining Pelabresib for Patients With Myelofibrosis

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July 9, 2023

Joseph Scandura, MD, PhD

Joseph M. Scandura, MD, PhD, Weill Cornell Medicine, discusses next steps for research of pelabresib (CPI-0610) for use in patients with myeloproliferative neoplasms.

Pelabresib is an oral, small molecule inhibitor of BET, which has the potential to downregulate the expression of genes that reside within the pathogenic pathways that underlie MPN progression.

One study evaluating pelabresib is the phase 3 MANIFEST-2 trial (NCT04603495). In this multicenter, double-blind, placebo-controlled trial, investigators are examining the safety and efficacy of pelabresib plus ruxolitinib (Jakafi) vs ruxolitinib alone in patients with JAK inhibitor-naïve myelofibrosis.

Patients aged 18 years and older with primary, post-polycythemia vera, or post-essential thrombocytopenia myelofibrosis, who had advanced disease requiring therapy, splenomegaly by computed tomography or magnetic resonance imaging, and were symptomatic were eligible for enrollment. Patients must also have had a prognostic risk-factor score of intermediate-1 or higher per the Dynamic International Prognostic Scoring System.

In the study, patients were randomly assigned in a 1:1 ratio to receive ruxolitinib in addition to oral pelabresib or matched placebo daily for 14 days, which was followed by 7 days off treatment. The starting dose of pelabresib was 125 mg daily. Then, ruxolitinib was given to patients twice a day in doses of 10 mg or 15 mg. Dose increases for both were allowed per protocol criteria.

Transcription:

0:10 | The first one is that we need to wait for the data to mature. My personal bias is, all of these biomarkers are invaluable until we know outcomes such as survival or time to treatment failure or event-free survival. Until we know that, we are just kind of stuck in this circular loop of what should be, what we hope will be, what our intuitive beliefs are, but we do not really know what any of these things mean until we have those outcomes. That just takes time.

0:46 | The nice thing is there are a number of phase 3 studies, randomized trials, collaborative studies. MANIFEST-2 is a randomized phase 3 study, and that will allow us to address and follow up on some of these findings, and hopefully get to those answers about whether or not these changes that we’re observing in the short-term are predicting these long-term beneficial outcomes. It just takes time for that data to mature

REFERENCE
Phase 3 study of pelabresib (CPI-0610) in myelofibrosis (MF) (MANIFEST-2) (MANIFEST-2). ClinicalTrials.gov. Updated April 6, 2023. Accessed July 6, 2023. https://clinicaltrials.gov/ct2/show/NCT04603495

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Navtemadlin With Ruxolitinib Leads to SVR Benefit in TP53 Wild-Type Myelofibrosis

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July 7, 2023

Kyle Doherty

The addition of the MDM2 inhibitor navtemadlin (formerly KRT-232) to ruxolitinib (Jakafi) led to clinically meaningful improvements in spleen volume reduction (SVR) among patients with primary or secondary TP53 wild-type myelofibrosis who had a suboptimal response to ruxolitinib, according to findings from the phase 1/2 KRT-232-109 study (NCT04485260) presented during the 2023 European Hematology Association (EHA) Congress.

Results from the trial showed that at 24 weeks among efficacy-evaluable patients (n = 19) adding navtemadlin to ruxolitinib conferred a minimum SVR of 25% in 42% of patients and an SVR of at least 35% in 32%. Additionally, a minimum total symptom score (TSS) improvement of at least 50% was observed in 32% of patients.

“This therapeutic approach is clearly active,” John O. Mascarenhas, MD, said. “The combination of navtemadlin and ruxolitinib achieves two things: synergy in terms of cell kill directed at the CD34 myeloblasts population, which is really what we’re trying to accomplish, and an improved toxicity profile [compared with] monotherapy. This is a combination that could potentially even be used upfront in the JAL inhibitor-naïve patient population. MDM2 inhibition is here and likely is going to be a component in the future. Navtemadlin is poised to be at the forefront as a first-in-class agent to deliver that kind of clinical activity.”

In an interview with OncLive®, Mascarenhas, professor of medicine at the Icahn School of Medicine at Mount Sinai, director of the Center of Excellence for Blood Cancers and Myeloid Disorders, and a member of Tisch Cancer Institute in New York, New York, discussed the design and rationale of KRT-232-109, more key findings from the trial, and potential future directions of the study.

OncLive: What is the mechanism of action of navtemadlin and what was the rationale for evaluating it in KRT-232-109?

Mascarenhas: Myelofibrosis is predominantly a TP53 wild-type disease. MDM2 negatively regulates TP53. [The] p53 pathway is important for regulating cell fate and balancing prosurvival and prodeath signals.

In myelofibrosis, MDM2 is overexpressed in CD34 cells, and this negatively regulates TP53 activity. It’s an alternative mechanism for cancer cells to increase the threshold for induction of apoptosis. Navtemadlin interrupts that interaction between MDM2 and wild-type TP53, thereby activating TP53 and inducing apoptosis.

What’s exciting about the phase 1b/2 study adding navtemadlin to patients receiving ruxolitinib with a suboptimal response is [the fact that] ruxolitinib works synergistically with navtemadlin in reducing p21. [This] essentially lowers the threshold to induce apoptosis in the setting of navtemadlin, so the two work well together to induce apoptosis in myelofibrosis CD34 cells—there’s great preclinical data that justify this concept.

What were the goals of the KRT-232-109 study?

The goal of the phase 1 was to determine the recommended phase 2 dose of navtemadlin in combination with ruxolitinib in these suboptimal ruxolitinib-[responding] myelofibrosis patients.

We evaluated 3 different dose levels and different dose schedules, and the recommended phase 2 dose based [not only] on the clinical results, but also on some of the pharmacokinetic results that were that were conducted is 240 mg of navtemadlin 7 days in a row of a 28-day cycle. [It’s a] 1-week-on-3-week-off [schedule of] 1-month cycles with the stable dose of ruxolitinib that the patient is on. So, you don’t adjust the dose of ruxolitinib, you simply add navtemadlin.

The ongoing purpose of the phase 2 [study] is to document the efficacy as measured by SVR and symptom improvement at 24 weeks.

What were some of the key inclusion criteria?

Patients had to have a platelet count greater than 100,000 because we often use platelet counts in these trials to determine eligibility. Patients had to have TP53 wild-type disease. Importantly, this approach is probably not effective in patients who have mutant disease because MBM2 doesn’t regulate mutant TP53. [Patients also needed to be] on ruxolitinib for at least 18 weeks, which is the minimal amount of time needed to determine whether someone has an optimal [response], suboptimal [response], or progressive disease, and at a stable dose of ruxolitinib for 8 weeks.

What were the key efficacy findings from KRT-232-109 presented during the 2023 EHA Congress?

We looked [what] we would normally look at in myelofibrosis, [such as] spleen response. The SVR [of] at least 35% at 24 weeks in evaluable patients was 32%. If you look at SVR [of at least] 25%, which is also considered by regulatory agencies a meaningful spleen response at 24 weeks, it was 42%. There was clear spleen reduction, and most patients [experienced] some degree of spleen response.

Symptom improvement was also seen; 32% of patients at week 24 had a 50% or greater TSS score and some of these patients had very significant spleen symptom burden at baseline. The drug was effective in addressing those 2 clinical end points.

What was really interesting was that patients, in some cases, had ruxolitinib doses of 5 mg twice daily going into the study, meaning they were coming in at low doses. And despite low doses of ruxolitinib, there was synergistic activity with navtemadlin[and] we were seeing very deep spleen and symptom responses. This speaks to the fact that biologically there is a priming almost of the diseased cells for TP53 induction of apoptosis with ruxolitinib. The preclinical data supported and translated very nicely into the clinical findings.

Are there any safety concerns clinicians should be aware of when using navtemadlin plus ruxolitinib?

[This was a] well-tolerated drug. We know that, as a class of agents, there is a degree of gastrointestinal [GI] toxicity with MDM2 inhibitors, [including] nausea, vomiting and diarrhea. [These events were] rarely grade 3/4 [in severity]; 70% of were grade 1. [Approximately] 60% of patients experienced some GI toxicity, usually in the first 2 cycles. Preemptively, we give antiemetic and an antidiarrheal. That is a very effective way of managing those nausea and diarrhea type toxicities.

The [inclusion] of ruxolitinib it seems to offset some of that toxicity. There may be some biologic reasons why there’s synergy with ruxolitinib, not just an efficacy, but also in improving the safety profile with navtemadlin. The deep responses that we see are also complemented by a well-tolerated combination.

What are the next steps for this research?

We want to finish the follow-up of patients enrolled in phase 2. We still have ongoing correlatives to look at. We presented correlatives that were very encouraging [showing] that we were having on-target stem cell–directed therapeutic effects, [such as] reduction of CD34 cell burden, reduction in bone marrow fibrosis, and reduction in driver RAF level in these patients that were treated.

We were clearly having disease-modifying effect, biologic response modification. We want to see that in a greater number of patients [and] I’d love to see some of the cytokine results. There’s still more to be done from a correlative science aspect and patient follow-up to be conducted.

Ultimately, where this will go is to a phase 3 study, which will be entitled BOREAS-2, where we’ll be [enrolling patients with] suboptimal ruxolitinib response and adding navtemadlin [and evaluating this treatment] vs placebo to improve responses.

Reference

Mascarenhas J, Jain T, Otoukesh S, et al. An open-label, global, phase (Ph) 1b/2 study adding navtemadlin (NVTM) to ruxolitinib (RUX) in patients (Pts) with primary or secondary myelofibrosis (MF) who have a suboptimal response to RUX. HemaSphere. 2023;7(suppl 3):S210.

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Phase 3 Trial of Selinexor and Ruxolitinib Starts in JAKi-Naive Myelofibrosis

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June 30, 2023

Jordyn Sava

A phase 3 clinical trial (NCT04562389) has been initiated to assess the efficacy and safety of selinexor (Xpovio) given once a week at 60 mg in combination with ruxolitinib (Jakafi) in JAK inhibitor (JAKi)-naïve patients with myelofibrosis, according to Karyopharm Therapeutics, Inc.1

The start of this phase 3 study is supported by phase 1 study results that showed rapid, deep, and sustained spleen responses and robust symptom improvement among patients at week 24 who were treated at the 60 mg dose level.

Findings revealed a 78.6% spleen volume response rate of ≥ 35% (SVR35) and 58.3% symptom improvement of ≥ 50% (TSS50) in the intent to treat patients, and SVR35 responses were observed in all 12 of the evaluable patients at any time. Additionally, rates were consistent regardless of subgroups, including patients treated with low dose ruxolitinib.

An improvement in major spleen and cytokine-related symptoms were observed and treatment with selinexor was generally well tolerated with a manageable adverse event (AE) profile. Most patients were able to remain on therapy for up to 74 weeks, and the most common treatment emergent AEs experienced with the 60 mg selinexor dose with ruxolitinib included nausea (78.6%), anemia (64.3%), thrombocytopenia (64.3%) and fatigue (57.1%).

The most common treatment-emergent grade ≥3 AEs with the combination with ruxolitinib were anemia (42.9%), thrombocytopenia (28.6%), and back pain (14.3%). Moreover, 75% of nausea events were grade 1 and did not lead to treatment-related discontinuations.

“The substantial degree of spleen volume reduction observed across all subgroups with selinexor 60 mg in combination with ruxolitinib is very encouraging. There is a significant unmet need in the treatment of patients with myelofibrosis, and these data demonstrate that the addition of XPO1 inhibition with selinexor with standard-of-care ruxolitinib has the potential to significantly improve outcomes for first-line myelofibrosis patients,” said John Mascarenhas, MD, professor of medicine at the Icahn School of Medicine at Mount Sinai and director of the Center of Excellence for Blood Cancers and Myeloid Disorders, in a press release. “As the principal investigator for the phase 3 study, I look forward to defining a potential new standard of care for JAK-naïve patients [with myelofibrosis].”

In the randomized, double-blind, placebo-controlled phase 3 study, approximately 306 JAKi-naive patients with intermediate or high-risk myelofibrosis will be enrolled and randomized in a 2:1 fashion to receive ruxolitinib plus selinexor 60 mg or ruxolitinib plus placebo in 28-day cycles.2

Enrollment in the study is open to patients aged 18 years and older with a diagnosis of primary myelofibrosis, post-essential thrombocythemia, or post polycythemia vera myelofibrosis who have a measurable splenomegaly during the screening period, an international prognostic scoring system risk category of intermediate-1, or intermediate-2, or high-risk, an ECOG performance status of less than or equal to 2, and a life expectancy of greater than 6 months. Additionally, patients must have active symptoms of myelofibrosis, and provide bone marrow biopsy samples at screening and during the study.

The coprimary end points of the study include SVR35 and TSS50 at week 24. The key secondary end point of the study is anemia response at week 24 with other secondary end points for the phase 3 portion including overall survival, overall response rate, pharmacokinetics, and number of patients with AEs.

The study is currently recruiting patients in Virginia and is active at sites in California, Tennessee, and Utah. The estimated study completion date is December 2027.

Top-line data are expected to read out from this phase 3 study in 2025, and the company plans to further investigate selinexor in other frontline opportunities, including in combinations for the treatment of myelofibrosis.1

“Selinexor and ruxolitinib appear to work synergistically, resulting in meaningful improvements in spleen response and total symptom score for patients with myelofibrosis,” said Reshma Rangwala, MD, PhD, chief medical officer of Karyopharm, in a press release. “We believe that an opportunity exists to expand upon the initial response, depth, and duration of JAK inhibitors to ultimately improve patient outcomes. This combination has the potential to become a cornerstone treatment in frontline myelofibrosis and we are excited to start this pivotal trial to deliver on our goal of bringing forward an innovative new approach for the treatment of myelofibrosis that can benefit [patients with myelofibrosis].”

REFERENCES:
  1. Karyopharm initiates pivotal phase 3 study of XPO1 inhibitor selinexor and ruxolitinib in JAK inhibitor (JAKi) naïve myelofibrosis. News release. Karyopharm Therapeutics, Inc. June 28, 2023. Accessed June 30, 2023. https://tinyurl.com/4phpud2y
  2. Study of selinexor in combination with ruxolitinib in myelofibrosis. ClinicalTrials.gov. Updated June 29, 2023. Accessed June 30, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04562389

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Jaktinib shows promise in treatment of myelofibrosis

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June 23, 2023

David Statman

In this video, Idoroenyi Amanam, MD, discussed a study presented at ASCO Annual Meeting, examining the treatment of anemia in myelofibrosis patients.

Amanam, an assistant professor in the Division of Leukemia at City of Hope Cancer Center, highlighted a study that examined the effects of jaktinib (Suzhou Zelgen Biopharmaceuticals Co, Ltd) versus hydroxyurea in patients with intermediate to high-risk myelofibrosis, with a primary endpoint of spleen volume reduction.

“From a response and efficacy perspective, jaktinib appears to be promising,” Amanam said. “What they have right now is exciting, and it’s another option in a space where we don’t have too many options.”

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FDA Extends Review Period for Momelotinib NDA in Myelofibrosis

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June 16, 2023

Kristi Rosa

The FDA has extended the review period for the new drug application (NDA) seeking the approval of momelotinib as a potential therapeutic option in patients with myelofibrosis.1 The regulatory agency pushed the decision date back by 3 months, to September 16, 2023, to allow for more time to review recently submitted findings.

The application was based on data from the phase 3 MOMENTUM trial (NCT04173494), in which momelotinib significantly improved symptoms, spleen size, and anemia vs danazol in patients with symptomatic and anemic myelofibrosis who received a prior JAK inhibitor.2

Specifically, more patients who received momelotinib (n = 130) experienced a reduction in tumor symptom score (TSS) of 50% or higher at week 24 vs those who were given danazol (n = 65), at 25% and 9%, respectively (proportion difference, 16%; 95% CI, 6%-26%; P = .0095), which met the primary end point of superiority with momelotinib. Moreover, more patients on the investigative arm achieved transfusion independence (TI) at week 24 than those on the control arm, at 30% (95% CI, 22%-39%) and 20% (95% CI, 11%-32%), respectively (noninferiority difference, 14%; 95% CI, 2%-25%; 1-sided P = .0016); TI rates from baseline to week 24 increased by 17% with momelotinib compared with 5% with danazol.

Momelotinib also demonstrated superiority over danazol with regard to splenic response rates at week 24. Thirty-nine percent of patients who received momelotinib experienced a reduction of 25% or more in spleen volume from baseline to week 24 vs 6% in those given danazol (P < .0001); moreover, 22% and 3% of patients, respectively, experienced a reduction of 35% or more (P = .0011).

In a recent news release, GlaxoSmithKline, the drug developer, stated that they were “confident in the momelotinib NDA” and that they “look forward to working with the FDA as they finalize their review.”1

The international, double-blind, randomized, controlled MOMENTUM trial enrolled patients with a confirmed diagnosis of primary myelofibrosis, post-polycythemia vera myelofibrosis, or post–essential thrombocytopenia myelofibrosis who were at least 18 years of age and who received a prior approved JAK inhibitor for at least 90 days.2

Patients were symptomatic, defined as a TSS of at least 10 at screening; were anemic, defined as a hemoglobin of less than 10 g/dL; a platelet count of more than 25 x 109 cells/L; and had splenomegaly at baseline. Moreover, patients had an ECOG performance status of 0 to 2, and could have had high-risk, intermediate2-risk, or intermediate-1 risk disease by Dynamic International Prognostic Scoring System criteria.

Study participants were randomly assigned 2:1 to momelotinib at 200 mg once daily or danazol at 300 mg twice daily.

The primary end point of the trial was week-24 TSS response rate, which was defined as the proportion of participants achieving a reduction in mean TSS of at least 50% over the 28 days prior to the end of week 24 vs baseline. Important secondary end points comprised week-24 TI rate, 25% splenic response rate at week 24, change in TSS from baseline to week 24, 35% splenic response rate at week 24, and rate of zero transfusions at week 24. Other end points focused on anemia, transfusions, survival, and safety.

A total of 195 patients were enrolled in the trial and were treated. Of those in the momelotinib and danazol arms, 72% and 58% of patients, respectively, completed treatment. The most common reason for early discontinuation in these arms was toxicity (12% vs 17%), followed by patient decision (5% vs 8%).

Data from the study were published in The Lancet and have a data cutoff date of December 3, 2021.

In all patients, the median baseline age was 71 years (interquartile range, 66-76), and most were male (63%) and White (81%). Moreover, the majority of patients had primary myelofibrosis (64%), intermediate-2 risk disease (57%), and harbored a JAK2 mutation (76%). Fourteen of the patients were TI and 50% were dependent. The mean duration of prior JAK inhibition in these patients was 2.6 years, and all patients previously receives ruxolitinib (Jakafi). Five percent of patients had prior fedratinib (Inrebic). The mean TSS at baseline was 27.2, mean hemoglobin was 8.0 g/dL, and the mean platelet count was 144.7 x 109 cells/L.

Additional findings indicated that in the group of patients who were transfusion dependent at baseline (n = 168), 26% and 15% of those in the momelotinib and danazol arms, respectively, achieved TI by the end of week 24.

Momelotinib also proved to be superior to danazol with regard to mean TSS change from baseline to end of week 24, at –11.5 vs –3.9, respectively (least squares mean difference, –6.2; 95% CI, –10.0 to –2.4; P = .0014). This was also true for the rate of zero transfusions to week 24, at 35% (95% CI, 27%-44%) and 17% (95% CI, 9%-28%), respectively (P = .0012). There was also a higher rate of zero transfusions at week 24 in those with hemoglobin at least 8 g/dL vs those with less than 8 g/dL (49% vs 21%) with momelotinib and with danazol (24% vs 9%).

Currently, momelotinib is not approved in any market.1

References

  1. GSK announces extension of FDA review period of momelotinib. News release. GlaxoSmithKline. June 16, 2023. Accessed June 16, 2023. https://www.gsk.com/en-gb/media/press-releases/gsk-announces-extension-of-fda-review-period-for-momelotinib/
  2. Verstovsek S, Gerds AT, Vannuchi AM, et al. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. Lancet. 2023;401(10373):269-280. doi:10.1016/S0140-6736(22)02036-0

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Dr Kremyanskaya on the Efficacy of Rusfertide in Phlebotomy-Dependent Polycythemia Vera

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June 16, 2023

Marina Kremyanskaya, MD, PhD

Marina Kremyanskaya, MD, PhD, assistant professor of medicine, hematology, and medical oncology, Icahn School of Medicine, Mount Sinai, medical director, Inpatient Oncology Unit, The Mount Sinai Hospital, discusses key efficacy data for rusfertide (PTG-300) in the phase 2 REVIVE trial (NCT04057040) of phlebotomy-dependent polycythemia vera.

Polycythemia vera is a specific type of erythrocytosis that also features systemic symptoms and a high risk of thromboembolic and/or cardiovascular (CV) complications. High levels of the iron-regulator hepcidin have been implicated in uncontrolled red blood cell formation.

The REVIVE trial compared the ability of the first-in-class hepcidin mimetic rusfertide vs placebo to control erythrocytosis in patients with polycythemia vera who had previously received 3 or more phlebotomies in 28 weeks with or without concurrent cytoreductive therapy. The trial was composed of a dose-finding stage (part 1), blinded randomized withdrawal (part 2), and an open-label extension portion (part 3).

Patients in part 1 received a weekly subcutaneous dose of rusfertide that was individually adjusted to achieve a hematocrit level below 45% (range, 10 mg-120 mg). In part 2, patients were randomized to continue rusfertide or to receive placebo. The study’s primary end point was efficacy as characterized by the proportion of responders in part 2, Kremyanskaya says. Responses were achieved if patients had a hematocrit level below 45% without phlebotomy eligibility, did not receive therapeutic phlebotomy, and had completed 12 weeks of treatment, she explains.

Results from the randomized withdrawal phase were presented at the 2023 EHA Congress and demonstrated that rusfertide produced a significantly higher percentage of responders vs placebo, Kremyanskaya reports. These percentages were 69.2% (n = 18/26) with rusfertide vs 18.5% (n = 5/27) with placebo. Additionally, most patients on the study had low ferretin levels at baseline, indicating iron deficiency, Kremyanskaya states. After treatment with rusfertide, ferretin levels were normalized and maintained for many of these patients, she says.

Analysis of symptom improvement was based on data from part 1, as the majority of patients in the placebo arm of part 2 discontinued treatment prior to the 12-week mark, Kremyanskaya continues. Rusfertide treatment significantly improved the rate and severity of problems with concentration, itching, fatigue, and inactivity, which tend to be moderate or severe at baseline. Regarding safety, the agent was generally well tolerated, Kremyanskaya concludes.

Disclosures: Dr Kremyanskaya reported receiving honoraria and being on the advisory board for Protagonist Therapeutics, Inc.

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Pacritinib Provides Spleen, Symptom Reduction Regardless of Blood Counts, Association Between SVR and OS in Myelofibrosis

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June 16, 2023

Caroline Seymour

Spleen volume reduction (SVR) was associated with overall survival (OS) with pacritinib (Vonjo) in patients with myelofibrosis. Treatment with the JAK2 inhibitor also demonstrated comparable improvements in spleen and symptom response regardless of baseline platelet counts and hemoglobin levels, according to findings from the pivotal phase 3 PERSIST-1 (NCT01773187) and PERSIST-2 (NCT02055781) trials that were presented at the 2023 ASCO Annual Meeting.1,2

Symptoms of myelofibrosis include marrow fibrosis, splenomegaly, and progressive cytopenia and prior approved agents include ruxolitinib (Jakafi) and fedratinib (Inrebic).

“The previous 2 JAK inhibitors ruxolitinib and fedratinib were for patients at a certain platelet cutoff, so that’s 50 [x 109/L] and above, and pacritinib ended up becoming approved for patients with myelofibrosis with platelets less than 50 [x 109/L], filling that urgent unmet medical need,” Naveen Pemmaraju, MD, associate professor in the Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, said in an interview with OncLive®.

Pacritinib is a JAK1-sparing inhibitor of JAK2/IRAK1/ACVR1 associated with improved SVR vs best available therapy (BAT), including ruxolitinib, in patients with myelofibrosis with platelets below 100 x 109/L in the PERSIST-2 trial. However, the relationship between SVR and OS in patients with thrombocytopenia is not well known. As such, investigators evaluated whether SVR with pacritinib or BAT is associated with improved survival in those with thrombocytopenia.

The analysis included patients from PERSIST-2 who were alive and on study who had received 200 mg of pacritinib twice daily or BAT at week 10 (week-12 SVR window).

In the pivotal PERSIST-2 trial, baseline characteristics in the pacritinib arm for responders (n = 65) and nonresponders (n = 24), respectively, were presented for age (median in years: 66 vs 67), Dynamic International Prognostic Scoring System (DIPSS) high risk (18.5% vs 46%), platelet count (median, 58 x 109/L vs 67 x 109/L), hemoglobin (median, 9.7 g/dL vs 9.3 g/dL), red blood cell transfusion requirement (38% vs 58%), prior JAK2 exposure (45% vs 50%), spleen volume (median, 2573 cm3 vs 2094.5 cm3), and palpable spleen length (median, 15.00 cm vs 12.75 cm).

Responders (n = 28) and nonresponders (n = 56) in the BAT arm had median ages of 66 years and 69 years, respectively. Moreover, 21% and 25% of patients, respectively, had DIPSS high-risk disease, median platelet counts of 68 x 109/L and 47 x 109/L, median hemoglobin of 10.0 g/dL and 9.6 g/dL, red blood cell transfusion requirement in 32% and 54%, prior JAK2 exposure in 64% and 45%, median spleen volume of 2907 cm3 and 2393 cm3, and median palpable spleen length of 12.00 cm and 14.50 cm.

Results showed that at least 10% SVR with pacritinib was prognostic for survival between responders and nonresponders (P <.0001). At least 20% and 35% or more SVRs were also prognostic for survival but to a lesser extent, with P values of .0199 and .3516, respectively. Authors also noted that any degree of SVR was associated with improved survival with pacritinib (HR, 0.08; 95% CI, 0.01-0.51; P = .0007).

Adjusting for baseline spleen volume and red blood cell transfusion requirement in univariate analysis did not affect the survival benefit with pacritinib at the 10% or greater SVR threshold.

Notably, SVR was not associated with survival with BAT at any threshold (SVR ≥10%, P =.4888; SVR ≥20%, P =.9821; SVR ≥35%, P =.8881).

“What is very encouraging is that we’re starting to see disease modification with these JAK inhibitors, not only showing spleen and symptom improvement, but also trying to show OS improvement and that the two can correlate,” Pemmaraju said. “Once we start to see spleen symptom improvement, as well as OS improvement, we can start to try to aim for and achieve disease modification, [which is] what matters to the patient. We’re starting to see that now, as we did with ruxolitinib and perhaps now with the newer JAK inhibitors.”

Additional findings from the analysis indicated that median dose intensity through week 12 was maintained with pacritinib at 200 mg twice daily in all patients who achieved SVR of at least 10%. Of the 28 patients who achieved SVR of at least 10% on BAT, the majority (n = 23) received ruxolitinib prior to the week-12 SVR evaluation. Of these patients, 78% were receiving no more than 10 mg of ruxolitinib twice daily and 43% were receiving no more than 5 mg of ruxolitinib twice daily. Other BATs included hydroxyurea (Hydrea) and prednisone.

Additionally, OS was associated with achieving at least 20% reduction in spleen length with pacritinib (HR, 0.14; 95% CI, 0.02-1.26; P =.0406; OS by spleen length reduction ≥35% and ≥50%, P =.0990 and P =.3008). However, separation of the curves was not as great for prognostication as SVR among responders and nonresponders.

“As pacritinib can be given at full dose regardless of platelet count, it is possible that pacritinib may offer a unique survival advantage for patients with myelofibrosis with moderate or severe thrombocytopenia who achieve ≥10% spleen reduction,” the authors wrote in the poster.

Although pacritinib is approved for use in patients with low platelet counts, clinical studies with the agent have included patients regardless of baseline anemia and thrombocytopenia. As such, another analysis was conducted, pooling the results of the PERSIST-1 and PERSIST-2 trials, to determine dosing patterns and efficacy outcomes by degree of baseline cytopenia.

Results showed that patients maintained median dose intensity of 100% regardless of whether they had baseline platelet counts below or above 100 x 109/L or baseline hemoglobin levels below 8 g/dL, between 8 g/dL and 10 g/dL, or 10 g/dL or above.

Additionally, between 21% and 28% of all patients, regardless of platelet and hemoglobin levels, achieved SVR of at least 35%; between 39% and 44% of patients achieved SVR of at least 25%; between 75.5% and 82% achieved SVR of at least 10%; and between 84% and 93% of patients achieved any spleen volume reduction. Moreover, the depth of the 24-week spleen reduction was similar across all platelet and hemoglobin strata.

Similarly, all patients achieved spleen reduction by week 12, and SVR remained consistent over time across all subgroups. Median hemoglobin also remained stable through week 24 across all hemoglobin thresholds, though some improvement was reported in patients with baseline levels below 8 g/dL.

Any improvement in total symptom score (TSS) was documented in between 80% and 87.5% of patients across all cytopenic groupings, although most patients with baseline hemoglobin below 8 g/dL (62.5%) derived the greatest magnitude in symptom improvement (TSS ≥50). Notably, 12-week TSS improvement occurred with deepening improvement through week 36, particularly in patients with baseline hemoglobin below 8 g/dL.

Regarding Patient Global Impression of Change response across all baseline blood count strata, approximately 80% of patients reported clinical improvement in disease symptoms and approximately 50% of patients classified their symptoms as “much” or “very much” improved at week 24.

“[This study] takes a look at the totality of the pacritinib data across doses across levels of cytopenias among patients and shows that while this drug is best known for its efficacy in cytopenic patients, it shows that the efficacy is about the same in those with higher blood counts as well, or at least it is certainly preserved in those patients as well,” Prithviraj Bose, MD, associate professor in the Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, told OncLive®.

References

  1. Ajufo H, Bewersdorf JP, Harrison C, et al. Spleen volume reduction (SVR) predicts overall survival (OS) in myelofibrosis (MF) patients on pacritinib (PAC) but not best available therapy (BAT): PERSIST-2 landmark OS analysis. J Clin Oncol. 2023;41(suppl 16):7018. doi:10.1200/JCO.2023.41.16_suppl.7018
  2. Bose P, Gagelmann N, Gupta V, et al. Consistency of pacritinib for spleen and symptom reduction in patients with myelofibrosis regardless of cytopenias. J Clin Oncol. 2023;41(suppl 16):7068. doi:10.1200/JCO.2023.41.16_suppl.7068

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