Zanubrutinib, in Combination With Lenalidomide, With or Without Rituximab in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

A Phase 1, Open Label, Multiple Dose, Dose Escalation and Expansion Study of Bruton Tyrosine Kinase (BTK) Inhibitor, Zanubrutinib, in Combination With Lenalidomide, With or Without Rituximab in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

The primary objective of this study is to determine the maximum tolerated doses (MTD) and the recommended Phase 2 dose (RP2D), and safety and tolerability of zanubrutinib in combination with lenalidomide in participants with R/R DLBCL by dose escalating lenalidomide

Study Overview

• Status: Completed
• Conditions: Relapsed/Refractory Diffuse Large B-Cell Lymphoma
• Intervention / Treatment: Drug: Zanubrutinib; Drug: Lenalidomide

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: BeiGene; Phone Number: 1-877-828-5568; Email: ClinicalTrials@beigene.com

Study Locations

• China
  • Guangzhou, China, 510060
    • Sun Yat-sen University Cancer Center
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center
  • Shanghai, China, 200120
    • Shanghai East Hospital
  • Tianjin, China, 300060
    • Tianjin Medical University Cancer Institute and Hospital
  • Beijing
    • Beijing, Beijing, China
      • Beijing Friendship Hospital, Capital Medical University
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Jilin
    • Changchun, Jilin, China, 130021
      • Jilin Cancer Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital · Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Zhejiang Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Histologically confirmed DLBCL, all participants must provide sufficient archival or fresh tumor tissue samples for evaluation by immunohistochemistry (IHC) and Gene Expression Profiling (GEP).
2. Relapsed or refractory disease, defined as either: 1) progression of disease after having achieved disease remission (complete response [CR] or partial response [PR]) , or 2) stable disease (SD), or progressive disease (PD) at completion of the treatment regimen preceding entry to the study.
3. Participants who have not received high dose therapy/stem cell transplantation (HDT/SCT) must be ineligible for HDT/SCT.
4. Measurable disease as defined by at least 1 lymph node >1.5 cm in longest diameter, or at least 1 extra-nodal lesion >1.0 cm in longest diameter, and measurable in 2 perpendicular dimensions.
5. Received an appropriate first-line therapy for DLBCL,defined as an anti CD20 antibody and an appropriate anthracycline-based combination therapy for at least 2 cycles, unless the patient is intolerant or had disease progression before Cycle 2..

Key Exclusion Criteria:

1. Current or history of central nervous system (CNS) lymphoma.
2. Histologically transformed lymphoma.
3. History of allogeneic stem-cell transplantation.
4. Prior exposure to a BTK inhibitor.
5. Prior exposure to lenalidomide or thalidomide.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 : Zanubrutinib + Lenalidomide; Zanubrutinib for up to 48 months Lenalidomide on Days 1 - 21 of each 28-Day cycle for up to 48 months	Drug: Zanubrutinib; 160 mg administered orally twice daily (BID); Other Names: BGB-3111; Drug: Lenalidomide; Administered as specified in the treatment arm
Experimental: Part 2 : Zanubrutinib+Lenalidomide; Zanubrutinib for up to 48 months Lenalidomide at the RP2D dose determined from Part 1 administered on Days 1 - 21 of each 28-Day cycle for up to 48 months	Drug: Zanubrutinib; 160 mg administered orally twice daily (BID); Other Names: BGB-3111; Drug: Lenalidomide; Administered as specified in the treatment arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants Experiencing Adverse Events (AEs)		Up to 48 months
Part 1: Number of Participants Experiencing Severe Adverse Events (SAEs)		Up to 48 months
Part 2: Overall Response Rate (ORR)	The proportion of participants who achieve either a partial response (PR) or complete response (CR)	Up to 48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Overall Response Rate (ORR)	The proportion of participants who achieve either a partial response (PR) or complete response (CR)	Up to 48 months
Area Under the Curve from Zero to Last Measurable Concentration (AUC0-t)		Cycle 1 Day 1 (C1D1) and C1D21 up to 8 hours post-dose
Maximum Concentration (Cmax)		C1D1 and C1D21 up to 8 hours post-dose
Time to reach maximum plasma concentration (Tmax)		C1D1 and C1D21 up to 8 hours post-dose
Apparent Clearance (CL/F)		C1D1 and C1D21 up to 8 hours post-dose
Receptor Occupancy (Ro)		C1D1 and C1D21 up to 8 hours post-dose
Complete Response Rate (CRR)		Up to 48 months
Time to Response (TTR)		Up to 48 months
Progression-Free Survival (PFS)		Up to 48 months
Duration of Response (DOR)		Up to 48 months

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Hui Yao, MD, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2020
• Primary Completion (Actual): March 28, 2024
• Study Completion (Actual): March 28, 2024

Study Registration Dates

• First Submitted: June 16, 2020
• First Submitted That Met QC Criteria: June 16, 2020
• First Posted (Actual): June 17, 2020

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Lenalidomide; Zanubrutinib
• Other Study ID Numbers: BGB-3111-110

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No