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

NCT04436107 | Completed Phase 1 Results

• 1 other identifier: BGB-3111-110
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 10

Brief Summary

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

Conditions

Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Part 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

  An adverse event (AE) is defined as any untoward medical occurrence in a patient temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with lenalidomide). A serious adverse event (SAE) is 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. * Was considered a significant medical AE by the investigator based on medical judgement (eg, may have jeopardized the patient or may have required medical/surgical intervention to prevent one of the outcomes listed above).

  From first dose of study drug to 30 days after last dose. Maximum time on treatment in Part 1 was 1260 days.

• Part 2: Overall Response Rate (ORR)

  ORR is defined as the percentage of participants who achieved a best overall response of partial response (PR) or complete response (CR) based on the Lugano classification as assessed by the investigator. Response was evaluated using computed tomography (CT) and metabolic imaging (fluorodeoxyglucose-positron emission tomography (FDG-PET)). CR: complete metabolic (no/minimal FDG uptake and no evidence of FDG-avid disease in bone marrow) and radiologic response (target lesions regressed to ≤ 1.5 cm in longest diameter with no extra-lymphatic sites of disease, no organ enlargement and normal bone marrow morphology), no new lesions, and no bone marrow involvement confirmed by bone marrow biopsies (if bone marrow was involved at baseline). PR is partial metabolic (reduced FDG uptake from Baseline) and radiologic response (≥ 50% decrease in size of measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by \> 50% in length beyond normal) and no new lesions.

  Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up was 24 months in Part 2 and 31 months in the RP2D group.

Secondary Outcomes (40)

• Part 1: Overall Response Rate (ORR)

  Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up in Part 1 was 42 months.

• Area Under the Plasma Concentration-time Curve From Zero to 8 Hours Postdose (AUCt) of Zanubrutinib After a Single Dose and at Steady State

  Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose

• Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Zanubrutinib After a Single Dose and at Steady State

  Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose

• Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Zanubrutinib After a Single Dose

  Cycle 1 Day 1, 0.5, 1, 2, 3, 4, and 8 hours postdose

• Maximum Plasma Concentration (Cmax) of Zanubrutinib After a Single Dose and at Steady State

  Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose

Study Arms (4)

Part 1: Zanubrutinib + Lenalidomide 15 mg

EXPERIMENTAL

Participants received zanubrutinib 160 mg orally twice a day (BID) and lenalidomide 15 mg orally once a day (QD) on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.

Drug: Zanubrutinib; Drug: Lenalidomide

Part 1: Zanubrutinib + Lenalidomide 20 mg

EXPERIMENTAL

Participants received zanubrutinib 160 mg orally BID and lenalidomide 20 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.

Drug: Zanubrutinib; Drug: Lenalidomide

Part 1: Zanubrutinib + Lenalidomide 25 mg

EXPERIMENTAL

Participants received zanubrutinib 160 mg orally BID and lenalidomide 25 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.

Drug: Zanubrutinib; Drug: Lenalidomide

Part 2: Zanubrutinib + Lenalidomide 25 mg

EXPERIMENTAL

Participants received zanubrutinib 160 mg orally BID and lenalidomide 25 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.

Drug: Zanubrutinib; Drug: Lenalidomide

Interventions

Zanubrutinib DRUG

160 mg administered orally twice daily (BID)

Also known as: BGB-3111, BRUKINSA

Part 1: Zanubrutinib + Lenalidomide 15 mg; Part 1: Zanubrutinib + Lenalidomide 20 mg; Part 1: Zanubrutinib + Lenalidomide 25 mg; Part 2: Zanubrutinib + Lenalidomide 25 mg

Lenalidomide DRUG

Administered orally on Days 1-21 each cycle followed by a mandatory 7-day drug-free interval.

Part 1: Zanubrutinib + Lenalidomide 15 mg; Part 1: Zanubrutinib + Lenalidomide 20 mg; Part 1: Zanubrutinib + Lenalidomide 25 mg; Part 2: Zanubrutinib + Lenalidomide 25 mg

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed DLBCL, all participants must provide sufficient archival or fresh tumor tissue samples for evaluation by immunohistochemistry (IHC) and Gene Expression Profiling (GEP).
• 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.
• Participants who have not received high dose therapy/stem cell transplantation (HDT/SCT) must be ineligible for HDT/SCT.
• 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.
• 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..

You may not qualify if:

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

Sponsors & Collaborators

• BeiGene: lead

Study Sites (10)

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, 100050, China

Location

Sun Yat Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

Location

Union Hospital of Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

Jilin Cancer Hospital

Changchun, Jilin, 130021, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200000, China

Location

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200120, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

zanubrutinib; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

1 877-828-5568

Study Officials

• Study Director

  BeiGene

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2020
• First Posted: June 17, 2020
• Study Start: September 11, 2020
• Primary Completion: March 28, 2024
• Study Completion: March 28, 2024
• Last Updated: May 23, 2025
• Results First Posted: May 23, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See plan description
• Access Criteria: See plan description

Locations

CN (10)