Inclusion Criteria:

1. Age ≥18 years. 2. Diagnosis of Primary or Secondary myelofibrosis (MF) according to the revised World Health Organization (WHO) criteria (Arber 2022). 3. Intermediate or high-risk disease. 4. 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. 5. 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). 6. 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. 7. Eastern Cooperative Oncology Group (ECOG) performance score 0-2. 8. Adequate hematologic function defined as: 1. absolute neutrophil count (ANC) ≥1.0 × 109/L (without growth factor support) 2. platelet count ≥50 × 109/L (Cohort 2 and Cohort 3 only) 9. 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). 10. 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:

Each participant must not meet any of the following: 1. Peripheral blood blast count of ≥10% or bone marrow blast count of ≥10%. 2. Prior history of hematopoietic stem cell transplant. 3. Participation in any other study in which receipt of an investigational new drug occurred within 4 weeks prior to Cycle 1 Day 1. 4. 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. 5. Known or suspected allergy to RVU120 or RUX. 6. Impairment of gastrointestinal function or gastrointestinal disease. 7. 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). 8. Ongoing systemic infection requiring antibiotic, antiviral, or antifungal treatment. Note: prophylactic treatment is allowed. 9. 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. 10. Taking any medications, herbal supplements, or other substances (including smoking) 11. History of ventricular arrhythmia, or QTc ≥470 millisecond (Bazett's formula). 12. Known active human immunodeficiency virus (HIV) infection. 13. Current active liver disease from any cause. 14. Pregnant or lactating females. 15. 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.

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.

Arms

Experimental: RVU120

Cohort 1 RVU120 is administered at 250 mg as a single agent every other day on days 1, 3, 5, 7, 9, 11, and 13 of 21-day treatment cycles, or at an adjusted dose, to participants with intermediate or high-risk, primary or secondary MF who have been previously treated with or are ineligible for treatment with a JAK inhibitor.

Experimental: RVU120 + ruxolitinib

Cohort 2 RVU120 is administered at 250 mg every other day on days 1, 3, 5, 7, 9, 11, and 13 of 21-day treatment cycles or at an adjusted dose, in combined with ruxolitinib administered orally twice daily following the dosing instructions in current prescribing information, to participants with intermediate or high risk, primary or secondary MF experiencing suboptimal response to JAK inhibitor.

Interventions

Drug: - RVU120

RVU120 is a potent, selective inhibitor of CDK8 and its paralog CDK19

Drug: - Ruxolitinib

Ruxolitinib is a kinase inhibitor which inhibits Janus Associated Kinases (JAKs) JAK1 and JAK2