A Phase I Clinical Study to Investigate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of BTK Inhibitor BGB-3111 in Chinese Patients With B-cell Lymphoma

BeiGene4 sites in 1 country44 target enrollmentJuly 5, 2016

ConditionsB-cell Lymphoma

InterventionsZanubrutinib

DrugsZanubrutinib

Overview

Phase: Phase 1
Intervention: Zanubrutinib
Conditions: B-cell Lymphoma
Sponsor: BeiGene
Enrollment: 44
Locations: 4
Primary Endpoint: Part I: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This phase I clinical study was to investigate the safety, tolerability, and pharmacokinetics/pharmacodynamics of Bruton tyrosine kinase (BTK) inhibitor zanubrutinib (BGB-3111) in Chinese participants with B-cell lymphoma by conducting in two stages, the first stage being the safety assessment of dose and the second stage being the dose expansion.

Part I: Safety evaluation - according to the results of preclinical toxicological trials and the results of the phase I clinical study conducted in Australia and New Zealand, two regimens of zanubrutinib 320 milligrams (mg) daily (160 mg twice daily [BID]), administered in the morning and at night, or 320 mg once daily [QD]) and "3+3" design was adopted for the assessment. The recommended dose and method of administration of the phase II clinical study was determined according to the Part I results.

Part II: Dose expansion - this stage was to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with follicular lymphoma (FL) or marginal zone lymphoma (MZL), approximately 20 participants with relapsed or refractory FL or MZL were to be enrolled. The recommended Phase 2 dose (RP2D) was used in Part II.

Registry

clinicaltrials.gov

Start Date

July 5, 2016

End Date

August 26, 2020

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

BeiGene

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Men and women between the age of 18-75 years.
•Participants with B-cell lymphoma (defined by World Health Organization classification) refractory or relapsed following at least one line of therapy.
•Judged by the investigator as requiring treatment.
•Eastern Cooperative Oncology Group performance status of 0-
•Life expectancy of at least 4 months.
•Adequate hematological function.
•Adequate renal function.
•Adequate liver function.
•Adequate coagulation function.
•Female participants of childbearing potential and non-sterile males must have practiced 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, intrauterine device or hormonal contraceptive initiated at least 3 months prior to first dose of study drug.

Exclusion Criteria

•With central nervous system involvement of the disease.
•The pathological type of the disease had disease transformation.
•Had underdone allogeneic hematopoietic stem cell transplantation.
•Had received corticosteroid anti-neoplastic treatment within 7 days before the first dose, has received radiotherapy and chemotherapy within 4 weeks before the first dose or has received treatment with monoclonal antibody within 4 weeks before the first dose.
•Had received BTK inhibitor treatment prior to enrollment.
•Had received chemotherapy and has not yet recovered from toxicity
•Had received Chinese herbal medicine as anti-neoplastic therapy within 4 weeks before starting study treatment.
•History of other malignancies within 2 years before study.
•With uncontrolled systemic infection.
•Major surgery in the past 4 weeks.

Arms & Interventions

Part I: 160 mg BID

Safety Evaluation: Two regimens of zanubrutinib 320 milligrams (mg) daily (160 mg twice daily \[BID\]) administered in the morning and at night, or 320 mg (once daily \[QD\]), and a "3+3" design was adopted for Part I of the study to determine recommended Phase 2 dose (RP2D).

Intervention: Zanubrutinib

Part I: 320 mg QD

Safety Evaluation: Two regimens of zanubrutinib 320 mg daily (160 mg BID, administered in the morning and at night, or 320 mg QD) and a "3+3" design was adopted for Part I of the study to determine RP2D.

Intervention: Zanubrutinib

Part II: 160 mg BID

Dose Expansion: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with follicular lymphoma (FL) or marginal zone lymphoma (MZL).

Intervention: Zanubrutinib

Outcomes

Primary Outcomes

Part I: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events

Time Frame: From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)

All adverse events were treatment emergent and were defined as an adverse event with a reported onset time or increase in severity after the initial dose of study drug and within 30 days after the last dose of study drug or initiation of new anticancer therapy, whichever was sooner. A serious adverse event was any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is significant medical event requiring intervention. All toxicity and adverse events were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 (NCI-CTCAE v4.03) grading criteria. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.

Part II: Partial Response Rate (PRR) Of Zanubrutinib In Participants With FL And MZL