Inclusion Criteria for Ruxolitinib Alone Period:

• Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by the treating physician according to the World Health Organization (WHO) criteria
• High, Intermediate-1, Intermediate-2 risk category International Prognosis System Score (IPSS)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• JAK-inhibitor treatment naive

Exclusion Criteria for Ruxolitinib Alone Period:

• Prior Splenectomy
• Splenic irradiation within 3 months prior to the first dose
• Prior BCL-XL, BET, MDM2, PI3K, PIM, or XPO1 inhibitors therapy or p53-directed therapy
• Eligible for Bone Marrow Transplant
• Peripheral blood or bone marrow blast count ≥ 10 percent

Inclusion Criteria for Randomized Period:

• PMF, post-PV MF, or post-ET MF that is TP53WT as assessed by central testing
• ECOG performance status of 0 to 2
• Treatment with a stable dose of ruxolitinib
• Suboptimal response to run-in ruxolitinib treatment

Exclusion Criteria for Randomized Period:

• Elevated white blood cell count that doubles (or more) during ruxolitinib treatment and exceeds 50 × 10^9/L
• Peripheral blood or bone marrow blast count ≥ 10 percent