RVU120 in Patients With Intermediate or High-risk, Primary or Secondary Myelofibrosis

Prior treatment

• 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.
• 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).
• 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 Day 1.

Other illness

• Known or suspected allergy to RVU120 or RUX.
• Impairment of gastrointestinal function or gastrointestinal disease
• Ongoing systemic infection requiring antibiotic, antiviral, or antifungal treatment. Note: prophylactic treatment is allowed.
• Known active human immunodeficiency virus (HIV) infection
• Current active liver disease from any cause

Lab values

• Peripheral blood blast count of ≥10% or bone marrow blast count of ≥10%.
• 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 (Section 17), or left ventricular ejection fraction (LVEF) <40% as per echocardiography or multiple gated acquisition (MUGA) scan.
• History of ventricular arrhythmia, or QTc ≥470 millisecond (Bazett's formula).
• 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.

Age

• Active known second malignancy with the exception of any of the following:
  • Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer
  • Adequately treated Stage I cancer from which the participant is currently in remission and has been in remission for ≥2 years
  • Low-risk prostate cancer with a Gleason score <7 and a prostate-specific antigen (PSA) level <10 ng/mL
  • Any other cancer from which the participant has been disease-free for ≥3 years.

Other

• Each participant must not meet any of the following:
• Pregnant or lactating females.

• 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 score 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 (see Section 15).
• 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.