PMD-026Therapeutic RSK1 Targeting in Myeloid Malignancies

Sponsor:

Washington University School of Medicine

Code:

NCT07379125

Conditions

Myeloid Malignancy

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

PMD-026

Study Details

Brief summary:

This study hypothesizes that PMD-026, an oral inhibitor of ribosomal protein S6 kinase A1 (RSK1), is safe and well tolerated in participants with myelofibrosis (MF) and myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPNs) and will improve spleen response, symptom response, and bone marrow histopathological response.

Conditions

Myeloid Malignancy

Study ID

NCT07379125

Start date

May 20, 2026

Status verified date

Oct, 2026

Completion date

Dec 31, 2028

Anticipated

Primary completion date

Dec 31, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Histologically confirmed diagnosis of one of the following myeloid neoplasms determined by pathology review:

Primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis in chronic phase according to the 2016 WHO criteria.

Patients with MF must have had at least 1 prior JAK inhibitor treatment for a minimum of 12 weeks and their disease must have been determined to be resistant or refractory, and/or their response must have been lost or intolerant to treatment.
MF must be Intermediate-2 or High-risk MF, as defined by the Dynamic International Prognostic Scoring System (DIPSS).
Chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, myelodysplastic / myeloproliferative neoplasm with ring sideroblasts and thrombocytosis, juvenile myelomonocytic leukemia, or myelodysplastic / myeloproliferative neoplasm unclassifiable according to the 2016 WHO criteria
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 OR 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
Blasts ≤ 10% on manual differential
The effects of PMD-026 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 30 days after completion of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria:

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).

Study Design

Enrollment

30 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment