POTAMI-61

CLINICAL STUDY

POTAMI-61

An Open-Label Clinical Trial of RVU120 as Monotherapy and in Combination With Ruxolitinib in Patients With Intermediate or High-Risk, Primary or Secondary Myelofibrosis (POTAMI-61).
TREATMENT
RVU120 and ruxolitinib (mono and combo) in myelofibrosis
STUDY OVERVIEW
Targeting CDK8/19 by RVU120 is a promising therapeutic strategy in myeloproliferative neoplasms. CDK8 kinase is an important player in MPN pathogenesis, as it regulates the activity of STAT proteins. By inhibiting CDK8, RVU120 disrupts the downstream signaling events mitigating
MPN symptoms.

In preclinical studies, RVU120 effectively reduced splenomegaly, bone marrow fibrosis, and abnormal blood cell production. When used in combination with JAK inhibitors, RVU120 may offer enhanced therapeutic benefits through a synergistic effect. RVU120 has also erythroid stimulating activity and demonstrated a favorable safety profile on normal hematopoiesis, making it a potential candidate for a broad clinical use in treating MPNs

More details on the completed Phase I/II clinical study in myelofibrosis can be found at ClinicalTrials.gov under NCT06397313
MILESTONE
Initial Phase II data in 2Q25

Eligibility criteria for the POTAMI-61 clinical trial

Study population

Women and man 18 Years and older.

Study design

The study schedule consists of a screening period up to 28 days, a 21-day treatment period, an end of treatment visit (30 days) and a 1-year follow-up where participants will be contacted every 3 months for assessment. Study duration for each participant will vary depending on the number of 21-day treatment cycles received.

The study is open to participants aged ≥18 years with intermediate or high-risk, primary or secondary MF who have been previously treated, are ineligible for, or had a suboptimal response to JAK inhibitor therapy. Participants must have adequate organ function (kidney, liver) and no history of hematopoietic stem cell transplant. Participants may withdraw from the study at any time at their own request or may be withdrawn at any time at the discretion of the Investigator.

WE WOULD LIKE TO INFORM YOU THAT RECRUITMENT FOR THE REMARK STUDY HAS BEEN COMPLETED.

Inclusion Criteria

Age ≥18 years
Diagnosis of Primary or Secondary myelofibrosis (MF) according to the revised World Health Organization (WHO) criteria (Arber 2022).
Intermediate or high-risk disease.
Resistant or refractory to prior Janus kinase (JAK) inhibitor treatment or ineligible for JAK inhibitor treatment in the opinion of the investigator; or Suboptimal response to JAK inhibitor treatment. Note: a suboptimal response to JAK inhibitor treatment is defined as spleen size increase by palpation >25% after the first 3 months of treatment with a JAK inhibitor or persistent splenomegaly (spleen volume of >450 cm3) after at least 6 months of JAK inhibitor treatment and presence of 1 symptom score ≥5 or 2 symptom scores ≥3, new or persistent red blood cell (RBC) transfusion dependence; or may include participants naïve to previous treatment with JAK inhibitor.
Measurable splenomegaly as demonstrated by palpable spleen measuring ≥5 cm below the left costal margin. The edge of the spleen should be measured from the mid-clavicular line on the left side of the abdomen to the point of greatest splenic protrusion; or spleen volume of ≥450 cm3 measured by magnetic resonance imaging (MRI) or computed tomography (CT).
Active symptoms of MF as demonstrated by a symptom score of at least 5 points (on a 0 to 10 scale) on at least one of the symptoms or a scores of 3 or greater on at least 2 of the following symptoms: night sweats, itchiness, abdominal discomfort, pain under ribs on left side, early satiety, bone or muscle pain, and inactivity.
Eastern Cooperative Oncology Group (ECOG) performance score 0-2.
Adequate hematologic function defined as: absolute neutrophil count (ANC) ≥1.0 × 109/L (without growth factor support) platelet count ≥50 × 109/L (Cohort 2 and Cohort 3 only)
Adequate renal function defined as calculated or measured creatinine clearance (CrCl) of ≥30 mL/minute using the formula of Cockcroft and Gault.
Adequate liver function defined as (a) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN); (b) alkaline phosphatase (ALP) ≤2 × ULN (ALP ≤5 × ULN for participants with isozymes specific to bone); (c) bilirubin <2 × ULN or bilirubin ≤3 × ULN if due to Gilbert’s disease.

Exclusion Criteria

Peripheral blood blast count of ≥10% or bone marrow blast count of ≥10%.
Prior history of hematopoietic stem cell transplant.
Participation in any other study in which receipt of an investigational new drug occurred within 4 weeks prior to Cycle 1 Day 1.
Active known second malignancy with the exception of any of the following:
1. Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer
2. Adequately treated Stage I cancer from which the participant is currently in remission and has been in remission for ≥2 years
3. Low-risk prostate cancer with a Gleason score <7 and a prostate-specific antigen (PSA) level <10 ng/mL
4. Any other cancer from which the participant has been disease-free for ≥3 years.
Known or suspected allergy to RVU120 or RUX.
Impairment of gastrointestinal function or gastrointestinal disease
Major surgical procedure or significant traumatic injury within 28 days Placement of a vascular access device or minor surgery is permitted within 14 days before Cycle 1 Day 1 (provided that the wound has healed).
Ongoing systemic infection requiring antibiotics, antiviral, or antifungal treatment. Note: prophylactic treatment is allowed.
Significant cardiac dysfunction defined as myocardial infarction within 12 months of Cycle 1 Day 1, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled dysrhythmias, poorly controlled angina, or left ventricular ejection fraction (LVEF) <40% as per echocardiography or multiple gated acquisition (MUGA) scan.
Taking any medications, herbal supplements, or other substances (including smoking) that are known to be strong inhibitors or moderate/strong inducers or sensitive substrates of CYP1A2, within less than 5 half-lives prior to Cycle 1.
History of ventricular arrhythmia, or QTc ≥470 millisecond (Bazett formula).
Known active human immunodeficiency virus (HIV) infection.
Current active liver disease from any cause.
Pregnant or lactating females.
Any other prior or current medical or psychiatric condition, intercurrent illness, surgical history, physical or electrocardiogram (ECG) findings, laboratory abnormalities, or extenuating circumstance (e.g., alcohol or drug addiction) that, in the Investigator’s opinion, could jeopardize participant safety or interfere with the objectives of the study.

Participation criteria are verified by the investigator. Participation in the study is contingent upon meeting all inclusion criteria and meeting none of the exclusion criteria. The criteria provided may not be a complete list.

Contact

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If you are a medical professional, an investigator for a RYVU trial, or would like information about becoming an investigator, please contact us at [email protected] or use contact form.