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

NCT02569476 | Completed Phase 1 Results DMC

• 1 other identifier: BGB-3111_GA101_Study_001
• Study Type: interventional
• Target: 119
• Locations: 3 countries
• Sites: 14

Brief Summary

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

Conditions

B-cell Lymphoid Malignancies

Keywords

BGB-3111; Zanubrutinib; Obinutuzumab; Lymphoma; Leukemia; Therapeutic uses; B-cell

Outcome Measures

Primary Outcomes (5)

• Part 1 : Number Of Participants Experiencing Adverse Events

  An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study drug. A serious AE (SAE) was any untoward medical occurrence that, at any dose. * resulted in death, * was life threatening, * required hospitalization or prolongation of existing hospitalization, * resulted in disability/incapacity, * was a congenital anomaly/birth defect.

  Day 1 (first dose) through 4 years and 8 months

• Part 1: Number Of Participants With Clinical Laboratory Abnormalities

  Laboratory results are reported as participants with shifts towards (high directionality) or away (low directionality) from Grade 3 or Higher Toxicity.

  Day -28 to -1 (predose) through 4 years and 8 months

• Part 1: Number Of Deaths

  An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. An SAE was any untoward medical occurrence that, at any dose: * resulted in death, * was life threatening, * required hospitalization or prolongation of existing hospitalization, * resulted in disability/incapacity, * was a congenital anomaly/birth defect.

  Day 1 (first dose) through 4 years and 8 months

• Part 1: Number Of Participants Experiencing Dose-limiting Toxicity (DLT)

  Dose-limiting toxicities were defined as a toxicity or AE occurring during the DLT assessment period (first 29 days of treatment), which is not clearly attributable to a cause other than zanubrutinib and/or obinutuzumab (such as disease progression, underlying illness, concurrent illness or concomitant medication) and meets one of the following criteria: * Grade 3 or 4 drug-related non-hematologic toxicity (excluding Grade 3 nausea, vomiting, hypertension, and asymptomatic laboratory abnormalities), * Grade 4 drug-related hematologic toxicity persisting for \>14 days, * any grade toxicity, which in the judgment of the investigator or Sponsor, required removal of the participant from the study.

  Day 1 (first dose) through 4 years and 8 months

• Part 1 and Part 2: Number Of Participants Achieving A Best Response Of Partial Response

  Partial response was defined as follows: * ≥ 50% reduction of serum IgM from baseline, * reduction in lymphadenopathy/splenomegaly (if present at baseline). For response assessments that occurred during cycles where a CT scan was not required, then results from prior scans (up to 12 weeks during the first 48 weeks and up to 24 weeks thereafter) could be carried forward in those participants with extramedullary disease at baseline.

  Day 1 (first dose) through 4 years and 8 months

Secondary Outcomes (19)

• Part 1 and Part 2: Number Of Participants Achieving A Best Response Of Complete Response

  Day 1 (first dose) through 4 years and 8 months

• Part 1 and Part 2: Progression-free Survival (PFS)

  Day 1 (first dose) through 4 years and 8 months

• Part 1 and Part 2: Duration Of Response (DOR)

  Day 1 (first dose) through 4 years and 8 months

• Part 1 and Part 2: Time To Response (TTR)

  Day 1 (first dose) through 4 years and 8 months

• Part 1 and Part 2: Overall Survival (OS)

  Day 1 (first dose) through 4 years and 8 months

Study Arms (1)

Zanubrutinib and Obinutuzumab

EXPERIMENTAL

In the dose-escalation part, dose levels and regimens were evaluated. In the indication-specific expansion cohorts, participants were assigned to different cohorts based on histology type.

Drug: Zanubrutinib; Drug: Obinutuzumab

Interventions

Zanubrutinib DRUG

Also known as: BGB-3111

Zanubrutinib and Obinutuzumab

Obinutuzumab DRUG

Zanubrutinib and Obinutuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BeiGene: lead

Study Sites (14)

Florida Cancer Specialists Fort Myers

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Specialists East

West Palm Beach, Florida, 33401, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37205, United States

Location

St George Hospital

Kogarah, New South Wales, 2217, Australia

Location

Brisbane Clinic For Lymphoma

Greenslopes, Queensland, 4120, Australia

Location

Ashford Cancer Centre Research Northeast

Windsor Gardens, South Australia, 5087, Australia

Location

St Vincents Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Barwon Health the Geelong Hospital

Geelong, Victoria, 3220, Australia

Location

St Frances Xavier Cabrini Hospital

Malvern, Victoria, 3144, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Asan Medical Center

Seoul, Seoul Teugbyeolsi, 05505, South Korea

Location

Gangnam Severance Hospital, Yonsei University Health System

Seoul, Seoul Teugbyeolsi, 06273, South Korea

Location

Samsung Medical Center

Seoul, Seoul Teugbyeolsi, 06351, South Korea

Location

Related Publications (1)

• Tam CS, Quach H, Nicol A, Badoux X, Rose H, Prince HM, Leahy MF, Eek R, Wickham N, Patil SS, Huang J, Prathikanti R, Cohen A, Elstrom R, Reed W, Schneider J, Flinn IW. Zanubrutinib (BGB-3111) plus obinutuzumab in patients with chronic lymphocytic leukemia and follicular lymphoma. Blood Adv. 2020 Oct 13;4(19):4802-4811. doi: 10.1182/bloodadvances.2020002183.

  PMID: 33022066 DERIVED

MeSH Terms

Conditions

Lymphoma; Leukemia

Interventions

zanubrutinib; obinutuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Study Director

  BeiGene

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2015
• First Posted: October 6, 2015
• Study Start: January 13, 2016
• Primary Completion: September 2, 2020
• Study Completion: September 2, 2020
• Last Updated: October 26, 2024
• Results First Posted: November 3, 2021

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

AU (8); KR (3); US (3)