Study of the Safety and Pharmacokinetics of BGB-3111 in Subjects With B-Cell Lymphoid Malignancies

Inclusion criteria

• Aged ≥ 18 years, voluntarily consented to the study.
• WHO classification defined B-lymphoid malignancy, with the exception of Burkitt lymphoma/leukemia, plasma cell myeloma, acute lymphoblastic leukemia, lymphoblastic lymphoma, and plasmablastic lymphoma.
• Requirement for treatment in the opinion of the investigator.
• Disease which has relapsed, or is refractory, following at least one line of therapy, with no therapy of higher priority available.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Adequate hematologic function, as defined by neutrophils ≥ 1.0 x 10^9/L and platelets ≥ 50 x 10^9/L; participants with neutrophils < 1.0 x 10^9/L due to marrow infiltration are allowed to receive growth factors to bring pre-treatment neutrophils to ≥ 1.0 x 10^9/L.
• Adequate renal function, as defined by creatinine clearance of ≥ 30 ml/min (as estimated by the Cockcroft-Gault equation or as measured by nuclear medicine scan or 24 hour urine collection).
• Adequate liver function, as defined by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN), and bilirubin ≤ 1.5 x ULN (unless documented Gilbert's syndrome).
• International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (APTT) ≤ 1.5 x ULN.
• Female participants of childbearing potential and non-sterile males must practice at least one of the following methods of birth control with partner(s) throughout the study and for 90 days after discontinuing study drug: total abstinence from sexual intercourse, double-barrier contraception, IUD or hormonal contraceptive initiated at least 3 months prior to first dose of study drug.
• Male participants must not donate sperm from initial study drug administration, until 90 days after drug discontinuation.

Exclusion criteria

• Current central nervous system (CNS) involvement by disease
• Current histologically transformed disease.
• Prior Bruton's tyrosine kinase (BTK) inhibitor treatment.
• Allogeneic stem cell transplantation within 6 months, or has active graft-versus-host disease (GVHD) requiring ongoing immunosuppression.
• Receipt of the following treatment prior to first dose of zanubrutinib: corticosteroids given with anti-neoplastic intent within 7 days, chemotherapy or radiotherapy within 2 weeks, monoclonal antibody within 4 weeks.
• Not recovered from toxicity of any prior chemotherapy to grade ≤ 1.
• History of other active malignancies within 2 years of study entry, with exception of (1) adequately treated in-situ carcinoma of cervix; (2) localized basal cell or squamous cell carcinoma of skin; (3) previous malignancy confined and treated locally (surgery or other modality) with curative intent.
• Uncontrolled systemic infection requiring parenteral anti-microbial therapy.
• Major surgery in the past 4 weeks.
• Known HIV, or active hepatitis B or hepatitis C infection (detected positive by PCR).
• Cardiovascular disease resulting in New York Heart Association function status of ≥ 3.
• Significant active renal, neurologic, psychiatric, hepatic or endocrinologic disease that in the investigator's opinion would adversely impact on his/her participating in the study.
• Inability to comply with study procedures.
• On medications which are cytochrome P450 (CYP) 3A inhibitors.