BGB 3111 in Combination With Obinutuzumab in Participants With B-Cell Lymphoid Malignancies

A Phase 1b Study to Assess Safety, Tolerability and Antitumor Activity of the Combination of BGB 3111 With Obinutuzumab in Subjects With B-Cell Lymphoid Malignancies

This study evaluated the safety and preliminary efficacy of BGB-3111 (zanubrutinib) in combination with obinutuzumab in participants with B-cell lymphoid malignancies.

Inclusion Criteria:

• Aged ≥18 years, able and willing to provide written informed consent and to comply with the study protocol.

• Laboratory parameters as specified below:

  • Hematologic: Platelet count >40x10^9/liter (L) (may be post-transfusion); absolute neutrophil count >1.0x10^9/L (growth factor use is allowed to bring pre-treatment neutrophils to >1.0x10^9 cells/L if marrow infiltration is involved).
  • Hepatic: Total bilirubin <3 x upper limit normal (ULN); and aspartate aminotransferase and alanine transaminase ≤3 x ULN.
  • Renal: Creatinine clearance ≥50 milliliters/minute (as estimated by the Cockcroft Gault equation or as measured by nuclear medicine scan or 24-hour urine collection); participants requiring hemodialysis will be excluded.

• Anticipated survival of at least 6 months.

• Eastern Cooperative Oncology Group performance status of 0 to 2.

• Female participants of childbearing potential and non-sterile males must have agreed to practice at least one of the following methods of birth control with partner(s) throughout the study and for ≥3 months after discontinuing zanubrutinib or ≥18 months following obinutuzumab treatment, whichever was longer: total abstinence from sexual intercourse, double barrier contraception, intra uterine device or hormonal contraceptive initiated at least 3 months prior to first administration of study drug.

• Male participants must have not donated sperm from first study drug administration, until 3 months after zanubrutinib discontinuation or 18 months following obinutuzumab treatment, whichever is longer.

Exclusion Criteria:

• Known central nervous system lymphoma or leukemia.
• Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome.
• Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
• History of significant cardiovascular disease.
• Severe or debilitating pulmonary disease.
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy.
• Prior Bruton tyrosine kinase inhibitor treatment.
• Used medications which were strong cytochrome P450 (CYP) 3A inhibitors and strong CYP3A inducers.
• Vaccination with a live vaccine within 28 days of the initiation of treatment.
• Allogeneic stem cell transplantation within 6 months, or had active graft versus host disease requiring ongoing immunosuppression.
• Receipt of the following treatment prior to first administration of zanubrutinib, corticosteroids given with anti-neoplastic intent within 7 days, chemotherapy or radiotherapy within 3 weeks, monoclonal antibody within 4 weeks.
• Participated in any investigational drug study within 28 days of study entry, or not recovered from non-hematologic toxicity of any prior chemotherapy up to ≤ Grade 1 (except for alopecia).
• History of other active malignancies within 2 years of study entry.
• Major surgery in the past 4 weeks.
• Active symptomatic fungal, bacterial and/or viral infection including evidence of infection with human immunodeficiency virus, human T cell lymphotropic virus seropositive status.
• Inability to comply with the study procedures.
• Pregnant or nursing women.
• Any illness or condition that in the opinion of the investigator may have affected the safety of treatment or evaluation of any study's endpoints.