Study of Oral Navitoclax Tablet in Combination With Oral Ruxolitinib Tablet Versus Best Available Therapy to Assess Change in Spleen Volume in Adult Participants With Relapsed/Refractory Myelofibrosis

Inclusion Criteria:

• Must complete the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 on at least 4out of the 7 days immediately prior to the date of randomization and must agree tocollect MFSAF data daily by ePRO device during the study collection window.

-- Has at least 2 symptoms each with an average score >= 3 or an average total scoreof >= 12, as measured by the MFSAF v4.0.

• Documented diagnosis of primary myelofibrosis (MF) as defined by the World HealthOrganization (WHO) classification, post polycythemia vera (PPV)-MF, or postessential thrombocytopenia (PET)-MF, characterized by bone marrow fibrosis grades 2or 3.

• Classified as intermediate-2 or high-risk MF, as defined by the DynamicInternational Prognostic Scoring System Plus (DIPSS+).

• Must currently be on treatment or have received prior treatment with a single JanusKinase 2 (JAK2) inhibitor, ruxolitinib, and meet one of the following criteria (inaddition to the minimum splenomegaly and symptom burden also required foreligibility):

• Treatment with ruxolitinib for >= 24 weeks that was stopped due to lack ofspleen response (refractory), or loss of spleen response or symptom controlafter a previous response (relapsed), or was continued despiterelapsed/refractory status.

• Treatment with ruxolitinib for < 24 weeks with documented disease progressionwhile on therapy as defined by any of the following:

• Appearance of new splenomegaly that is palpable to at least 5 cm below theleft costal margin (LCM) in participants with no evidence of splenomegalyprior to the initiation of ruxolitinib.

• A >= 100% increase in the palpable distance below the LCM in participantswith measurable spleen distance 5 to 10 centimeters (cm) prior to theinitiation of ruxolitinib.

• A >= 50% increase in the palpable distance below the LCM in participantswith measurable spleen distance > 10 cm prior to the initiation ofruxolitinib.

• A spleen volume increase of >= 25% (as assessed by Magnetic ResonanceImaging [MRI] or Computed Tomography [CT] scan) in participants with aspleen volume assessment prior to the initiation of ruxolitinib.

• Prior treatment with ruxolitinib of at least 10 mg twice daily (BID) for >= 28days with intolerance defined as new RBC transfusion requirement (at least 2units/month for 2 months) while receiving a total daily ruxolitinib dose of >= 30 mg but unable to reduce dose further due to lack of efficacy.

Note: Participant must not require a ruxolitinib dose less than 10 mg BID (20 mg daily) due to prior history of ruxolitinibrelated ≥ Grade 3 toxicity.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

• Splenomegaly defined as palpable spleen measurement >= 5 cm below left costal marginor spleen volume >= 450 cm3 as assessed centrally by MRI or CT scan.

• Baseline platelet count >= 100 × 10^9/L.

Exclusion Criteria:

• Received prior treatment with a B-cell lymphoma 2 homology 3 (BH3)-mimetic compound,bromodomain and extra-terminal (BET) inhibitor, phosphoinositide 3- kinase andtelomerase inhibitors (e.g., parsaclisib), prior use of > 1 JAK2 inhibitor or stemcell transplant.

• Eligible for stem cell transplantation at the time of study entry.

• Receiving medication that interferes with coagulation or platelet function within 3days prior to the first dose of study drug or during the study treatment periodexcept for low dose aspirin (up to 100 mg daily) and low molecular weight heparin (LMWH).

• Receiving anticancer therapy for an active malignancy or MF including chemotherapy,radiation therapy, hormonal therapy such that at least 5 half-lives of thatmedication is completed at least 7 days prior to the first dose of study drug orwithin 30 days prior to first dose of study drug, whichever is shorter, and duringthe study treatment period (other than any overlapping therapy as part of theselected BAT).