Safety and Tolerability Study of Oral ABBV-744 Tablet Alone or in Combination With Oral Ruxolitinib Tablet or Oral Navitoclax Tablet in Adult Participants With Myelofibrosis

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):

• >= 24 weeks duration of current ruxolitinib course, with evidence of disease that is resistant, refractory, or has lost response to ruxolitinib therapy;
• < 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.
• 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.