A Phase 3, Randomized, Double-blind, Add-on Study Evaluating the Safety and Efficacy of Navtemadlin Plus Ruxolitinib vs Placebo Plus Ruxolitinib in Patients with Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib
Subjects will start by receiving ruxolitinib alone in the run-in period. Those who demostrate a suboptimal response from ruxolitinib alone will then be randomized 2:1 to receive navtemadlin or navtemadlin placebo as add-on treatment to their ongoing ruxolitinib. Randomized means that subjects will be assigned to a group by chance, like a flip of a coin. The study is blinded, meaning the subjects, doctors, central endpoint assessors and sponsor will not know which add on treatment (navtemadlin or navtemadlin placebo) the subject is receiving.
Eligibility: Inclusion Criteria
• 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