Clinical Research Directory

Inclusion Criteria: * Laboratory values indicative of adequate bone marrow, renal, and hepatic function meeting protocol criteria. * Completion of the Myelofibrosis System Assessment Form (MFSAF) on at least 4 out of the 7 days prior to Day 1 with at least 2 symptoms with a score \>=3 or a total score of \>=10. * Documented diagnosis of intermediate or high-risk primary myelofibrosis (PMF), post-polycythemia vera MF (PPV-MF) or post-essential thrombocytopenia MF (PET-MF) as defined by the World Health Organization (WHO). * Eastern Cooperative Oncology Group (ECOG) Performance Status of \<= 2. * Intermediate - 2, or High-Risk disease as defined by the Dynamic International Prognostic Scoring System (For Segment A only, Intermediate - 1 with palpable splenomegaly \>=5 centimeters \[cm\] below costal margin are also eligible). * Splenomegaly defined as spleen palpation measurement \>= 5 cm below costal margin or spleen volume \>= 450 cubic cms as assessed by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) scan (for Segments A and C, baseline spleen assessment must be obtained \> 7 days after discontinuation of most recent Myelofibrosis (MF) therapy. If possible, this assessment should occur within 10 days of Cycle 1 Day 1). Segment-Specific Prior Therapy Criteria: * Segment A: * Prior exposure to one or more Janus Kinase inhibitors (JAKi),\[the most recent of which was discontinued \> 14 days prior to Cycle 1 Day 1\] and are intolerant, resistant, refractory or lost response to the JAKi. * Segment B: * Currently receiving ruxolitinib AND * Willingness to reduce ruxolitinib dose (if on a higher dose); and on a stable dose for 14 days or longer prior to Cycle 1 Day 1; AND * At least one of the following criteria (a, b, or c): 1. \>= 24 weeks duration of current ruxolitinib course, with evidence of disease that is resistant, refractory, or has lost response to ruxolitinib therapy; 2. \< 24 weeks duration of current ruxolitinib course with documented resistance, refractories, or loss of response, as defined by any of the following: * Appearance of new splenomegaly that is palpable to at least 5 cm below the left costal margin (LCM), in participants with no evidence of splenomegaly prior to the initiation of ruxolitinib. * \>=100% increase in the palpable distance below the LCM, in participants with measurable spleen distance 5 - 10 cm prior to the initiation of ruxolitinib. * \>=50% increase in the palpable distance below the LCM, in participants with measurable spleen \> 10 cm prior to the initiation of ruxolitinib. * A spleen volume increase \>= 25% (as assessed by MRI or CT) in participants with a spleen volume assessment available prior to the initiation of ruxolitinib. 3. Prior treatment with ruxolitinib for \>= 28 days complicated by any of the following: * Development of red blood cell transfusion requirement (at least 2 units/month for 2 months). * Grade \>= 3 adverse events of neutropenia and/or anemia while on ruxolitinib treatment, with improvement or resolution upon dose reduction. * Segment C: * Prior exposure to one or more JAKi (the most recent of which was discontinued \> 14 days prior to Cycle 1 Day 1), and are intolerant, resistant, refractory or lost response to the JAKi. Exclusion Criteria: Segment-Specific Prior Therapy Criteria: * Segment A: * Prior exposure to one or more Bromodomain and Extra-Terminal (BET) inhibitors. * Segment B: * Prior exposure to one or more BET inhibitors. * Segment C: * Prior exposure to one or more BET inhibitors and/or any B-Cell Lymphoma 2 (BCL)-2 and/or BCL- XL inhibitor, including navitoclax. * Segment D: * Prior exposure to JAKi and/or any BET inhibitor.