Tag Archives: clinical trial

Clinical Trial Aims to Test Tagraxofusp and Pacritinib Combination Therapy in Patients With MF

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Özge Özkaya, MSc, PhD
Publish Date

A new study testing the combination of tagraxofusp and pacritinib in patients with myelofibrosis (MF) is now open.

The single-center, open-label, early phase 1, pilot trial aims to recruit 20 patients with MF who are at least 18 years of age and who have previously been treated with a Janus kinase (JAK) 1/2 inhibitor or in whom JAK1/2 inhibitor therapy is not appropriate, is contraindicated, or was declined.

Participants will be given 12 µg/kg of intravenous tagraxofusp once a day for 3 consecutive days and 200 mg of oral pacritinib twice a day starting at the 4th day of the second cycle and administered continuously with subsequent cycles starting on day 1 of each cycle.

The primary outcome measures will be a spleen volume reduction of 35% of more and the change in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score Version 2.0 (MPN-SAF TSS 2.0) from baseline to week 24.

Secondary outcome measures will include the number of participants with treatment-related adverse events, the change from baseline in anemia and platelet count, and any improvement in patients’ quality of life based on the global impression of change.

Tagraxofusp is a cytotoxin directed at CD123, and pacritinib is a small-molecule kinase inhibitor. The rationale of using these 2 drugs in combination is their compatible mechanisms of action targeting MF stem cells and the bone marrow. It is thought that the combination may lead to improvements in symptoms associated with myeloproliferative neoplasms and reduce splenomegaly.

Both agents have previously been studied in cases of mildly depleted bone marrow and were shown to be safe and led to hematological improvements.

The trial is not yet recruiting participants but aims to recruit 20 participants. It is estimated to be completed in December 2026.

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Biomed Valley Discoveries Announces First Patient Dosed in Phase 1/2 Combination Study of Ulixertinib with Ruxolitinib (Jakafi®) in Patients with Myelofibrosis

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Provided by GlobeNewswire  

— Dual targeting of JAK 1/2 (ruxolitinib) and ERK 1/2 (ulixertinib) may represent a novel treatment approach for myelofibrosis and possibly other myeloproliferative neoplasms

KANSAS CITY, Mo., April 28, 2025 (GLOBE NEWSWIRE) — Biomed Valley Discoveries (BVD), a clinical-stage biotechnology company guided by its founders’ intent of bringing hope for life to patients, today announced that the first patient has been dosed in a Phase 1/2 combination study of ulixertinib, BVD’s highly selective, first-in-class ERK 1/2 inhibitor with ruxolitinib, a JAK1/JAK2 inhibitor for the treatment of myelofibrosis, a rare type of bone marrow cancer that disrupts the body’s normal production of blood cells.

Raajit Rampal, M.D., Ph.D., a hematologist-oncologist with Memorial Sloan Kettering Cancer Center who specializes in the treatment of myeloproliferative neoplasms and leukemia, is the lead principal investigator for this investigator-initiated trial.

“We’re thrilled to announce the milestone of first patient dosed in this trial, and grateful for the opportunity to collaborate with Dr. Rampal and Incyte to explore the potential of ERK inhibition as a complement to JAK inhibition for the treatment of patients with myelofibrosis,” said Brent Kreider, Ph.D., President of BVD. “This trial helps further our commitment to fully interrogate the potential of direct ERK inhibition to address unmet patient needs in various cancer settings where MAPK signaling is implicated.”

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Clinical Trials Can Open Doors for Patients With Myeloproliferative Neoplasms

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By Kathryn Johnson, DNP, MSc, FNP-BC
Fact checked by Bridget Hoyt

Educating patients on the “risks and benefits” of clinical trials is a part of the pipeline for better treatment options in myeloproliferative neoplasms (MPNs) in which nurses can engage, said a nurse practitioner.

For patients with MPNs, clinical trials have paved the way for better treatment outcomes, increasing options vastly within a short amount of time. In an interview with Oncology Nursing News, Kathryn Johnson, DNP, MSc, FNP-BC, spoke to the importance of the development of these options and nurses’ role in making those possible.

As Johnson, a clinical program manager at Icahn School of Medicine at Mount Sinai New York, outlined, nurses can play a key part in informing patients on what to expect on clinical trials. She advised not only being prepared with information patients should know, but making time for patients to air their concerns and ask questions as well.

Johnson added that in the time that she has been working in oncology, multiple advancements have been made in the treatment of MPNs. She expects this trend to continue in the coming years.

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Fedratinib Shows Promise in Long-Term MPN Success With Tolerable Toxicity

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By Hany Elmariah, MD

A phase 1 trial investigated the safety and tolerability of maintenance therapy with the JAK2 inhibitor fedratinib (Inrebic) following allogeneic hematopoietic cell transplant (HCT) for myeloproliferative neoplasms (MPNs) and myelodysplastic syndrome/MPN overlap syndromes.

While HCT offers potential cure for MPNs, posttransplant relapse remains a significant challenge. Fedratinib, effective in myelofibrosis, with a favorable safety profile and oral administration, presents a rational strategy to reduce relapse and potentially prevent graft-vs-host disease (GVHD) while preserving the graft-vs-tumor (GVT) effect.

“Usually with fedratinib, the main toxicities are cytopenia, so low blood counts. We also see a fair amount of [gastrointestinal (GI)] toxicity, nausea, vomiting, or diarrhea,” said Hany Elmariah, MD, associate member at the Moffitt Cancer Center in the Department of Bone Marrow Transplant and Cellular Immunotherapy, in an interview with Targeted OncologyTM.

The study enrolled patients post-HCT who received fedratinib between days +60 and +100 for up to 1 year. The trial utilized a 3+3 design to determine the maximum tolerated dose (MTD). Eleven patients were evaluable for dose-limiting toxicities (DLTs). The MTD was identified as 400 mg daily. While no DLTs occurred within the 30-day window, 4 patients withdrew due to non-DLT adverse events. Notably, only 1 patient developed severe chronic GVHD. The median progression-free survival was 12.4 months, and the 1-year overall survival was 100%.

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New Trial Will Assess Safety and Efficacy of MF Drug

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Leonardo Jaimes, MD

Publish Date

A clinical trial aiming to determine the efficacy, safety, and pharmacokinetics of the experimental drug WJ01024 combined with ruxolitinib in patients with myelofibrosis (MF) is set to begin soon.

“Although the clinical efficacy of ruxolitinib tablets has been confirmed, only about half of MF patients can achieve the ideal therapeutic effect (≥35% reduction in spleen volume and ≥50% improvement in disease symptoms at 24 weeks),” the authors wrote. “Therefore, there is an urgent need for innovative drugs that can be combined with ruxolitinib tablets to enhance therapeutic efficacy and meet clinical needs,” they added.

WJ01024 aims to enhance the therapeutic efficacy of ruxolitinib through  XPO-1 inhibition. Previous in vitro studies have confirmed that the drug enhances ruxolitinib anti-cell proliferation activity, the researchers noted. Furthermore, preliminary studies on humans suggest that WJ01024 is effective as monotherapy for relapsing patients and those intolerant to JAK inhibitors, they added.

The trial will consist of a dose escalation and a dose extension phase (phase 1a and phase 2). Phase 1b will divide patients into three groups receiving 40 mg, 60 mg, and 80 mg of WJ01024, respectively. Phase 2 will be an open-label evaluation of the efficacy and safety of the recommended dose in combination with ruxolitinib.

The study will only include patients diagnosed with MF and with the international prognostic scoring system risk category of intermediate-1, intermediate-2, or high-risk. Patients in the accelerated blast phase or previous treatment with either JAK or XPO-1 inhibitors are not eligible for participation.

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Pelabresib Plus Ruxolitinib Improves Spleen Responses in Myelofibrosis

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By Roman Fabbricatore
Fact checked by Russ Conroy

Pelabresib (CPI 0610) in combination with ruxolitinib (Jakafi) significantly improved spleen responses and elicited robust clinical activity compared with placebo/ruxolitinib in patients with JAK inhibitor-naïve myelofibrosis, according to results from the phase 3 MANIFEST-2 trial (NCT04603495) published in Nature Medicine.1

Efficacy data from the trial revealed that the primary end point of spleen volume reduction of at least 35% at week 24 favored the investigational combination vs the placebo arm: 65.9% vs 35.2%, respectively (difference, 30.4%; 95% CI, 21.6%-39.3%; P <.001). Additionally, the mean percent change at week 24 in the respective arms was –50.6% (95% CI, –53.2% to –48.0%) vs –30.6% (95% CI, –33.7% to –27.5%). Spleen volume response was consistently higher with pelabresib vs placebo across predefined subgroups.

Furthermore, the hemoglobin response rate, defined as a 1.5 g/dl or greater mean increase, occurred in in 10.7% of the pelabresib arm (95% CI, 6.60%-14.90%) vs 6.0% of the placebo arm (95% CI, 2.85%-9.19%). Transfusions were received in the first 24 weeks of treatment in 27.6% and 37.5% of respective arms.

Greater reductions in NF-κB-regulated cytokines (–32.1% [95% CI, –34.9% to –29.2%] vs –19.4% [95% CI, –22.5% to –16.2%]), tumor necrosis factor (TNF; –43.5% [95% CI, –47.0% to –39.8%] vs –26.4% [95% CI, –30.5% to –22.1%]), and interleukin-6 (IL-6; –35.4% [95% CI, –44.2% to –25.2%] vs –14.5% [95% CI, –25.2% to –2.3%]) were seen in the investigational arm vs the placebo arm. Of note, a reduction in IL-8 levels was observed with pelabresib (–14.3% [95% CI, –22.3% to –5.5%]), but an increase was observed in the placebo arm (31.2% [95% CI, 17.5%-46.5%).

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Promising New Treatment for Myelofibrosis Blood Cancer Using a Combination Targeted Therapy 

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By Julie Grisham

An international phase 3 clinical trial of a new drug combination for treating the blood cancer myelofibrosis found that adding a second, experimental drug to standard treatment was more effective than the standard treatment alone. Further, adding the second drug did not significantly increase side effects. Memorial Sloan Kettering Cancer Center (MSK) enrolled the most patients in the trial.

“This is one of the largest myelofibrosis clinical trials to date,” says MSK leukemia specialist Raajit Rampal, MD, PhD, lead author of the study, published March 10 in Nature Medicine. “There is a real unmet need for patients with this disease, and the findings from this trial represent an exciting advance.”

This study looked at adding an experimental drug called pelebresib to the drug ruxolitinib (Jakafi®), which is the current treatment for myelofibrosis. Both drugs are targeted therapies. Pelebrisib blocks the action of proteins involved in inflammation and cancer; ruxolitinib blocks a protein called JAK. This combination approach was based on ongoing research from the lab of MSK leukemia specialist and physician-scientist Ross Levine, MD.

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New MF Study Recruiting Participants for Its Phase 3 Portion

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Özge Özkaya, MSc, PhD
Publish Date

A phase 1/3 clinical trial testing the safety and efficacy of selinexor plus ruxolitinib in patients with myelofibrosis (MF) who are Janus kinase (JAK) inhibitor-naïve is now recruiting participants for its phase 3 portion.

The global, multicenter, 2-part study aims to recruit an estimated 350 participants with MF. Participants were all at least 18 years of age.

The study consists of an experimental phase 1a, experimental phase 1b, and experimental phase 3 portion.

In the experimental phase 1a portion, 1 group of patients were given 40 mg of oral selinexor once a week on days 1, 8, 15, and 22 of each 28-day cycle together with 15 or 20 mg of ruxolitinib twice a day based on their platelet count at baseline while another group was given 60 mg of oral selinexor on the same days and the same dose of ruxolitinib as the first group.

In the experimental phase 1b, patients were given either 40 or 60 mg of oral selinexor once a week on days 1, 8, 15, and 22 of each 28-day cycle and the same dose of ruxolitinib.

In the experimental phase 3 portion, patients will either be given a fixed starting dose of 60 mg of oral selinexor or a placebo once a week on days 1, 8, 15, and 22 of each 28-day cycle together with the same dose of ruxolitinib.

The primary outcome measures of the phase 1 portion of the trial was the maximum tolerated dose and recommended phase 2 dose of selinexor and the number of participants with adverse events by severity, nature, and occurrence.

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Protagonist and Takeda Announce Positive Topline Results from Phase 3 VERIFY Study of Rusfertide in Patients with Polycythemia Vera

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March 3, 2025

− Study met the primary endpoint, with a significantly higher proportion of clinical responders on rusfertide compared to placebo

− All four key secondary endpoints were met, including EU primary endpoint and patient-reported outcomes

− Rusfertide was generally well tolerated; no new safety findings were observed in the study

NEWARK, Calif. & OSAKA, Japan & CAMBRIDGE, Mass.–(BUSINESS WIRE)–Protagonist Therapeutics, Inc. (“Protagonist”) (NASDAQ:PTGX) and Takeda (TSE:4502/NYSE:TAK) today announced positive topline results for the Phase 3 VERIFY study, in which phlebotomy-dependent patients with polycythemia vera (PV) were randomized to treatment with either rusfertide or placebo, as an add-on to standard of care treatment. The study met its primary endpoint and all four key secondary endpoints. Rusfertide is a first-in-class investigational hepcidin mimetic peptide therapeutic, which has received Orphan Drug designation and Fast Track designation from the U.S. Food & Drug Administration (FDA).

Key findings from the study include:

  • The primary endpoint of the study was met, with a significantly higher proportion of clinical responders1 among rusfertide-treated patients with PV (77%) compared to those who received placebo (33%) during weeks 20-32; p<0.0001. The primary endpoint of the study was the proportion of patients achieving a response, which was defined as the absence of phlebotomy eligibility.
  • The first key secondary endpoint, which is the pre-specified primary endpoint for European Union (EU) regulators, was also met, with a mean of 0.5 phlebotomies per patient in the rusfertide arm compared to 1.8 phlebotomies per patient in the placebo arm during weeks 0-32; p<0.0001.
  • The other three pre-specified key secondary endpoints, namely hematocrit control2 and patient-reported outcomes using PROMIS Fatigue SF-8a3 and MFSAF TSS-74, were also achieved with statistical significance.
  • Rusfertide was generally well tolerated in the Phase 3 VERIFY trial, and safety was in line with previous rusfertide clinical studies. No new safety findings were observed in the study. The majority of adverse events were grade 1-2 injection site reactions and all serious adverse events reported were deemed to be not drug related. There was no evidence of an increased risk of cancer in rusfertide-treated patients compared to those on placebo.

“The positive results of the Phase 3 VERIFY study across the primary and all key secondary endpoints provide compelling evidence of the potential for rusfertide as a first-in-class erythrocytosis-specific agent to address unmet medical needs in patients with PV who are unable to achieve adequate hematocrit control despite standard of care treatments,” said Arturo Molina, M.D., M.S., Chief Medical Officer of Protagonist. “We plan to submit additional details of these promising results for presentation at upcoming medical conferences in 2025. We are immensely grateful to the patients, study staff and principal investigators who made the VERIFY study possible.”

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Bromodomain and BET Inhibitor INCB057643 Shows Benefit for Patients With Myelofibrosis

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12/19/24

Emily Estrada

According to research presented by Justin Watts, MD, Sylvester Cancer Center Institute, University of Miami, Miami, Florida at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego, California, INCB057643 may improve patient outcomes in the treatment of hematologic malignancies, including myelofibrosis (MF).

A small-molecular bromodomain and extra-terminal BET protein inhibitor, INCB057643, has shown safety and tolerability as monotherapy and combination with Janus kinase (JAK) 1 and 2 inhibitors among patients with MF in previous phases of the ongoing phase 1/2 clinical trial. In this dose-escalation and expansion portion of the trial, the dose of INCB057643 in patients with MF receiving monotherapy was increased from 4mg to 12mg and for patients with MF who had an inadequate response to ruxolitinib, combination therapy dosage was increased from 4mg to total maximum dosage.

The primary end points were safety and tolerability, as well as dose-limiting toxicities of INCB057643 at 24 weeks. The secondary end points included spleen volume reduction greater than 35% from baseline (SVR35), symptom reduction by greater than 50% from baseline via MPN-Symptom Assessment Form (TSS50), and anemia response of a hemoglobin increase at least 1.5 g/dL from baseline in patients that were not receiving transfusions or transfusion-free for at least 12 weeks for patients dependent on transfusions at baseline.

Patients with relapsed/refractory MF (84.1%%), essential thrombocythemia ([ET]; 4.5%), myelodysplastic syndromes (MDS), or myeloproliferative neoplasm (MPN) syndromes (11.4%). were included in the study. In total, 18 patients were treated with a monotherapy dose escalation and 10 patients received dose expansion. Combination therapy dose escalation was received by 16 patients whose median age was 71 years and whose median ruxolitinib dose was 22.4mg per day. The median duration of INCB057643 exposure was 195.5 days for patients in the monotherapy dose-escalation cohort and 139.0 days for patients in the dose-expansion cohort. As for patients who were in the combination therapy dose-escalation cohort, median INCB057643 exposure was 194.0  days.

At 24 weeks, 3 out of 16 patients who received monotherapy achieved SVR35 and 5 out of 14 achieved TSS50 with any dose of INCB057643, of which 3 received a dose of at least 10 mg. During any time of treatment, improvements in spleen volume and TSS50 best response were demonstrated by 13/19 and 12/15 patients, respectively. Among patients who received combination therapy of INCB057643 and ruxolitinib, 3 out of 12 patients achieved SVR35 and 6 out of 11 achieved TSS50 at any combo dose. Improvements were seen at any time during treatment for both SVR35 and TSS50 in 13 out of 16 and 10 out of 15 patients, respectively. Of patients not dependent on blood transfusions, an anemia response was demonstrated by 3 patients in both the monotherapy and the combination group. Additionally, of 6 patients who were blood transfusion dependent at BL, 2 achieved transfusion independence.

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