Therapeutic RSK1 Targeting in Myelofibrosis

NCT07379125 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202603106
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase Ib study evaluating PMD-026, an oral inhibitor of ribosomal protein S6 kinase A1 (RSK1), in participants with myelofibrosis (MF).The dose escalation portion utilizes a standard 3+3 design to evaluate two dose levels with an additional dose de-escalation portion to identify the recommended phase II dose (RP2D); subsequently, an additional 6 patients will be enrolled in the dose expansion portion evaluating the efficacy of PMD-026.

Conditions

Myelofibrosis

Keywords

Myelofibrosis; Primary Myelofibrosis; Secondary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis; Splenomegaly; Anemia; Spleen volume; Spleen; Hematologic Diseases; Bone Marrow Diseases; Bone Marrow Cancer; Myeloproliferative Neoplasm

Outcome Measures

Primary Outcomes (7)

• Number of participants with adverse events

  Graded per CTCAE v5.0.

  From cycle 1 day 1 through 28 days after last dose (estimated to be 1 year and 28 days)

• Number of participants with dose limiting toxicities (DLTs) based on occurrence of serious treatment-emergent adverse events (Dose Escalation only)

  Dose limiting toxicities are defined in the protocol.

  During cycle 1 of treatment (each cycle is 28 days)

• Recommended phase II dose (RP2D) (Dose Escalation only)

  The RP2D will be determined based on review of safety and tolerability endpoints in dose escalation.

  Completion of cycle 1 (each cycle is 28 days) of all dose-escalation patients (estimated to be 1 year and 28 days)

• Changes in spleen size (Dose Expansion and RP2D Cohort in Dose Escalation)

  Measured by ultrasound or other abdominal imaging.

  Baseline and after 24 weeks of treatment (estimated to be 24 weeks)

• Changes in Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 Total Symptom Score (Dose Expansion and PR2D Cohort in Dose Escalation)

  The MFSAF assesses patient's symptom burden with 7-items that are scored from 0 (Absent) to 10 (Worst Imaginable). The total score can range from 0-70 with the higher score meaning more severe symptoms.

  Baseline and after 24 weeks of treatment (estimated to be 24 weeks)

• Bone marrow histopathologic response (Dose Expansion and RP2D Cohort in Dose Escalation)

  Bone marrow histopathologic response will be evaluated by the International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria.

  Baseline and after 24 weeks of treatment (estimated to be 24 weeks)

• Overall response rate (ORR) (Dose Expansion and RP2D Cohort in Dose Escalation)

  Defined as CR (complete remission/response) + PR (partial remission/response) + CI (clinical improvement). Responses are defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) consensus.

  Baseline and after 24 weeks of treatment (estimated to be 24 weeks)

Secondary Outcomes (7)

• Percentage of patients with 35% or greater reduction in spleen volume as determined by ultrasound or other imaging modalities

  At 24 weeks and at the end of treatment (estimated to be 1 year)

• Percentage of participants with 25% or greater reduction in spleen volume as determined by ultrasound or other imaging modalities

  At 24 weeks and at the end of treatment (estimated to be 1 year)

• Percentage of patients with a 50% or greater improvement in Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) Total Symptom Score

  At 24 weeks and at the end of treatment (estimated to be 1 year)

• Percentage of patients with a reduction in National Institutes of Health Patient Reported Outcomes Measurement Information System (NIH PROMIS) Short Form v2.0 - Physical Function 8c 7-day scores

  At 24 weeks and at the end of treatment (estimated to be 1 year)

• Overall response rate (ORR)

  At 24 weeks and at the end of treatment (estimated to be 1 year)

Study Arms (4)

Dose Escalation Dose Level -1: PMD-026

EXPERIMENTAL

PMD-026 will be taken by mouth twice daily at the assigned dose every day of each 28-day cycle.

Drug: PMD-026

Dose Escalation Dose Level 1 (Starting Dose): PMD-026

EXPERIMENTAL

PMD-026 will be taken by mouth twice daily at the assigned dose every day of each 28-day cycle.

Dose Escalation Dose Level 2: PMD-026

EXPERIMENTAL

PMD-026 will be taken by mouth twice daily at the assigned dose every day of each 28-day cycle.

Drug: PMD-026

Dose Expansion - Recommended Phase II Dose (RP2D): PMD-026

EXPERIMENTAL

PMD-026 will be taken by mouth twice daily at the recommended phase II dose every day of each 28-day cycle.

Interventions

PMD-026 DRUG

PMD-026 is an oral drug which will be taken every 12 hours on an outpatient basis at the assigned dose every day of each 28-day cycle. Provided by Phoenix Molecular Designs.

Dose Escalation Dose Level -1: PMD-026; Dose Escalation Dose Level 2: PMD-026

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis in chronic phase, according to the 2016 WHO criteria
• Patients must have had at least 1 prior JAK inhibitor treatment for a minimum of 12 weeks and their disease was determined resistant or refractory, and/or their response was lost or intolerant to treatment.
• Intermediate-2 or High-risk MF, as defined by the Dynamic International Prognostic Scoring System (DIPSS).
• Presence of measurable disease as defined by:
• Splenomegaly defined as estimated spleen volume of ≥450 cm3 by imaging with either MRI, CT or ultrasound, or a palpable spleen \>=5 cm from the costal margin.
• Baseline MFSAF v4.0 Total Symptom Score ≥ 10
• At least 18 years of age.
• ECOG performance status ≤ 2.
• Adequate organ function as defined below:
• Total bilirubin ≤ 1.5 x IULN (unless the participant has a history of Gilbert's syndrome)
• AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
• Creatinine clearance ≥ 30 mL/min by Cockcroft-Gault
• Adequate laboratory parameters:
• Absolute Neutrophil Count (ANC) ≥ 100/mm\^3
• Platelets ≥50,000/mm\^3

You may not qualify if:

• Prior allogeneic or autologous stem cell transplantation within the previous 12 months
• Prior splenectomy
• Prior splenic irradiation if \< 3 months between last radiation and screening visit.
• Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
• Currently receiving any other investigational agents or planning to receive any investigational agents within 28 days before the planned first dose of PMD-026.
• Currently receiving a JAK inhibitor or planning to receive a JAK inhibitor within 7 days before the planned first dose of PMD-026. In patients with ongoing JAK inhibitor therapy (i.e. ruxolitinib) at screening, it must be tapered over a period of at least 7 days. Patients on a low dose of ruxolitinib (e.g. 5 mg QD) may have a reduced taper period or no taper.
• Known active disease involving the CNS.
• QTcF \>450 msec for males, \>470 msec for females (calculated using Fridericia's formula).
• A history of hypersensitivity or allergic reactions attributed to compounds of similar chemical or biologic composition to PMD-026 or other agents used in the study.
• Any major surgery within 28 days prior to the first dose of PMD-026.
• Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, autoimmune disease, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Unable to swallow or retain oral medications.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 35 days of study entry (repeated on C1D1).

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Phoenix Molecular Designs: collaborator
• The Foundation for Barnes-Jewish Hospital: collaborator
• Swim Across America: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Primary Myelofibrosis; Splenomegaly; Anemia; Hematologic Diseases; Bone Marrow Diseases; Bone Marrow Neoplasms; Myeloproliferative Disorders

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms

Study Officials

• Amy W Zhou, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy W Zhou, M.D.

CONTACT

314-362-8814; a.zhou@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2026
• First Posted: January 30, 2026
• Study Start (Estimated): May 31, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)