An Open-label, Phase 2 Study of ACP-196 in Subjects with Waldenström Macroglobulinemia

Exclusion Criteria

• 1. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for ≥2 years or which will not limit survival to <2 years. Note: These cases must be discussed with the medical monitor.
• 2. A life-threatening illness, medical condition, or organ system dysfunction which, in the investigator’s opinion, could compromise the subject’s safety, interfere with the absorption or metabolism of acalabrutinib, or put the study outcomes at undue risk.
• 3. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or QTc >480 msec.
• 4. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or gastric bypass, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
• 5. Any immunotherapy within 4 weeks of first dose of study drug.
• 6. For subjects with recent chemotherapy or experimental therapy, the first dose of study drug must occur after 5 times the half-life of the agent(s).
• 7. Prior exposure to a BCR inhibitor (e.g., BTK,PI3K, or SYK inhibitors) or BCL-2 inhibitors (e.g., ABT-199).
• 8. Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids for treatment of WM or other conditions. Note: Subjects may use topical or inhaled corticosteroids or low-dose steroids (≤10 mg of prednisone or equivalent per day) as therapy for comorbid conditions. During study participation, subjects may also receive systemic or enteric corticosteroids as needed for treatment-emergent comorbid conditions.
• 9. Grade ≥2 toxicity (other than alopecia) continuing from prior anticancer therapy including radiation.
• 10. Known history of HIV or active infection with HCV or hepatitis B virus (HBV) or any uncontrolled active systemic infection.
• 11. Major surgery within 4 weeks before first dose of study drug.
• 12. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
• 13. History of a bleeding diathesis (e.g., hemophilia, von Willebrand disease).
• 14. History of stroke or intracranial hemorrhage within 6 months before the first dose of acalabrutinib.
• 15. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 28 days of first dose of study drug.
• 16. Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).
• 17. ANC <0.75 x 109/L or platelet count <50 x 109/L. For subjects with disease involvement in the bone marrow, ANC <0.50 x 109/L or platelet count <30x109/L.
• 18. Creatinine >2.5 x institutional ULN; total bilirubin >2.5 x ULN; or AST or ALT >3.0 x ULN.
• 19. Lactating or pregnant.
• 20. Concurrent participation in another therapeutic clinical trial.