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, tolerability, and efficacy of zanubrutinib in combination with lenalidomide in participants with R/R DLBCL

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 Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat Sen University Cancer Center
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Jilin
    • Changchun, Jilin, China, 130021
      • Jilin Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai, China, 200120
      • Shanghai East Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • 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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Zanubrutinib + Lenalidomide 15 mg; 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; 160 mg administered orally twice daily (BID); Other Names: BGB-3111; BRUKINSA; Drug: Lenalidomide; Administered orally on Days 1-21 each cycle followed by a mandatory 7-day drug-free interval.
Experimental: Part 1: Zanubrutinib + Lenalidomide 20 mg; 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; 160 mg administered orally twice daily (BID); Other Names: BGB-3111; BRUKINSA; Drug: Lenalidomide; Administered orally on Days 1-21 each cycle followed by a mandatory 7-day drug-free interval.
Experimental: Part 1: Zanubrutinib + Lenalidomide 25 mg; 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; 160 mg administered orally twice daily (BID); Other Names: BGB-3111; BRUKINSA; Drug: Lenalidomide; Administered orally on Days 1-21 each cycle followed by a mandatory 7-day drug-free interval.
Experimental: Part 2: Zanubrutinib + Lenalidomide 25 mg; 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; 160 mg administered orally twice daily (BID); Other Names: BGB-3111; BRUKINSA; Drug: Lenalidomide; Administered orally on Days 1-21 each cycle followed by a mandatory 7-day drug-free interval.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Overall Response Rate (ORR)	ORR is defined as the percentage of participants who achieved a best overall response of partial response or complete response based on the Lugano classification as assessed by the investigator. Response was evaluated using CT and metabolic imaging (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 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	Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation (LLOQ) was 1.00 ng/mL.	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	Blood samples to characterize the PK profile of zanubrutinib and lenalidomide when given in combination were collected after first dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 1.00 ng/mL.	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	Blood samples to characterize the PK profile of zanubrutinib and lenalidomide when given in combination were collected after first dose (Cycle 1 Day 1) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 1.00 ng/mL.	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	Blood samples to characterize the PK profile of zanubrutinib and lenalidomide when given in combination were collected after first dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 1.00 ng/mL.	Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Time to Maximum Plasma Concentration (Tmax) of Zanubrutinib After a Single Dose and at Steady State	Blood samples to characterize the PK profile of zanubrutinib and lenalidomide when given in combination were collected after first dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 1.00 ng/mL.	Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Time to the Last Quantifiable Concentration (Tlast) of Zanubrutinib After a Single Dose and at Steady State	Blood samples to characterize the PK profile of zanubrutinib and lenalidomide when given in combination were collected after first dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 1.00 ng/mL.	Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Apparent Terminal Elimination Half-life (T1/2) of Zanubrutinib After a Single Dose and at Steady State	Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation (LLOQ) was 1.00 ng/mL.	Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Apparent Volume (CL/F) of Zanubrutinib After a Single Dose and at Steady State	Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation (LLOQ) was 1.00 ng/mL.	Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Apparent Clearance (Vz/F) of Zanubrutinib After a Single Dose and at Steady State	Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation (LLOQ) was 1.00 ng/mL.	Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Accumulation Ratio of AUCt for Zanubrutinib	Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation (LLOQ) was 1.00 ng/mL. Accumulation ratio is defined as the ratio of AUCt at steady state (Day 21) to the AUCt after the first dose (Day 1).	Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Accumulation Ratio of Cmax for Zanubrutinib	Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation (LLOQ) was 1.00 ng/mL. Accumulation ratio is defined as the ratio of Cmax at steady state (Day 21) to the Cmax after the first dose (Day 1).	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 Plasma Concentration-time Curve From Zero to 8 Hours Postdose (AUCt) of Lenalidomide After a Single Dose and at Steady State	Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.	Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
AUClast of Lenalidomide After a Single Dose and at Steady State	Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.	Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
AUCinf of Lenalidomide After a Single Dose	Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.	Cycle 1 Day 1 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Cmax of Lenalidomide After a Single Dose and at Steady State	Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.	Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Tmax of Lenalidomide After a Single Dose and at Steady State	Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.	Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Tlast of Lenalidomide After a Single Dose and at Steady State	Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.	Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
T1/2 of Lenalidomide After a Single Dose and at Steady State	Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.	Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
CL/F of Lenalidomide After a Single Dose and at Steady State	Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.	Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Vz/F of Lenalidomide After a Single Dose and at Steady State	Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.	Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Accumulation Ratio of AUCt for Lenalidomide	Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL. Accumulation ratio is defined as the ratio of AUCt at steady state (Day 21) to AUCt after the first dose (Day 1).	Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Accumulation Ratio of Cmax for Lenalidomide	Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL. Accumulation ratio is defined as the ratio of Cmax at steady state (Day 21) to Cmax after the first dose (Day 1).	Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Part 1: Overall Response Rate by Immunohistochemistry Subtypes	ORR is defined as the percentage of participants who achieved a best overall response of PR or CR based on the Lugano classification as assessed by the investigator. Response was evaluated using CT and metabolic imaging (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. Immunohistochemistry (IHC) was used to identify germinal B-cell-like (GCB) and non-GCB phenotypes.	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.
Part 1: Overall Response Rate by Gene Expression Profiling (GEP) Subtypes	The percentage of participants who achieved a best overall response of PR or CR based on the Lugano classification as assessed by the investigator. Response was evaluated using CT and metabolic imaging. 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: 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. Gene expression profiling by HTG EdgeSeq DLBCL cell-of-origin (COO) assay was used to determine activated B-cell like (ABC) and GCB subtypes.	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.
Part 2: Overall Response Rate by Immunohistochemistry Subtypes	ORR is defined as the percentage of participants who achieved a best overall response of PR or CR based on the Lugano classification as assessed by the investigator. 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 biopsy (if bone marrow was involved at baseline). PR: 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. Immunohistochemistry was used to identify GCB and non-GCB phenotypes.	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 31 months in the RP2D group.
Part 2: Overall Response Rate by Gene Expression Profiling Subtypes	ORR is defined as the percentage of participants who achieved a best overall response of PR or CR based on the Lugano classification assessed by the investigator. 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 biopsy (if bone marrow was involved at baseline). PR: 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. Gene expression profiling by HTG EdgeSeq DLBCL COO assay was used to determine ABC and GCB subtypes.	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 31 months in the RP2D group.
Part 2: Complete Response Rate (CRR)	CRR is defined as the percentage of participants who achieved a best overall response of complete response (CR) based on the Lugano classification as assessed by the investigator. Response was evaluated using CT and metabolic imaging (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).	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.
Part 2: Complete Response Rate by Immunohistochemistry Subtypes	CRR is defined as the percentage of participants who achieved a best overall response of complete response (CR) based on the Lugano classification as assessed by the investigator. Response was evaluated using CT and metabolic imaging (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). Immunohistochemistry was used to identify GCB and non-GCB phenotypes.	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 31 months in the RP2D group.
Part 2: Complete Response Rate by Gene Expression Profiling Subtypes	CRR is defined as the percentage of participants who achieved a best overall response of complete response (CR) based on the Lugano classification as assessed by the investigator. Response was evaluated using CT and metabolic imaging (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). Gene expression profiling by HTG EdgeSeq DLBCL cell-of-origin assay was used to determine ABC and GCB subtypes.	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 31 months in the RP2D group.
Part 2: Duration of Response (DOR)	DOR is defined as the time from the date that the response criteria were first met to the date that progressive disease (PD) was objectively documented or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method. Participants who did not have disease progression were censored at their last valid assessment. PD: Progressive metabolic disease (increased FDG uptake from Baseline and/or new FDG-avid foci consistent with lymphoma), abnormal node or lesions with longest diameter > 1.5 cm, an increase of ≥ 50% in the product of the perpendicular diameters, and an increase in the longest diameter of 0.5 cm for lesions ≤ 2 cm or 1.0 cm for lesions > 2 cm, or any new lesions.	From first dose to the end of study; maximum time on follow-up was 24 months in Part 2 and 31 months in the RP2D group.
Part 2: Duration of Response by Immunohistochemistry Subtypes	DOR is defined as the time from the date that the response criteria were first met to the date that progressive disease PD was objectively documented or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method. Participants who did not have disease progression were censored at their last valid assessment. Immunohistochemistry was used to identify GCB and non-GCB phenotypes.	From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.
Part 2: Duration of Response by Gene Expression Profiling Subtypes	DOR is defined as the time from the date that the response criteria were first met to the date that progressive disease PD was objectively documented or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method. Participants who did not have disease progression were censored at their last valid assessment. Gene expression profiling by HTG EdgeSeq DLBCL cell-of-origin assay was used to determine ABC and GCB subtypes.	From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.
Part 2: Progression-free Survival (PFS)	PFS is defined as the time from the starting date of the combination therapy to the date of first documentation of disease progression or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Participants who did not have disease progression were censored at their last valid tumor assessment.	From first dose to the end of study; maximum time on follow-up was 24 months in Part 2 and 31 months in the RP2D group.
Part 2: Progression-Free Survival by Immunohistochemistry Subtypes	PFS is defined as the time from the starting date of the combination therapy to the date of first documentation of disease progression or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Participants who did not have disease progression were censored at their last valid tumor assessment. Immunohistochemistry was used to identify GCB and non-GCB phenotypes.	From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.
Part 2: Progression-Free Survival by Gene Expression Profiling Subtypes	PFS is defined as the time from the starting date of the combination therapy to the date of first documentation of disease progression or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Participants who did not have disease progression were censored at their last valid tumor assessment. Gene expression profiling by HTG EdgeSeq DLBCL cell-of-origin assay was used to determine ABC and GCB subtypes.	From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.
Part 2: Time to Response (TTR)	Time to response is defined as time from the starting date of combination therapy to the date the response criteria were first met.	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.
Part 2: Time to Response by Immunohistochemistry Subtypes	Time to response is defined as time from the starting date of combination therapy to the date the response criteria were first met. Immunohistochemistry was used to identify GCB and non-GCB phenotypes.	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 31 months in the RP2D group.
Part 2: Time to Response by Gene Expression Profiling Subtypes	Time to response is defined as the time from the starting date of combination therapy to the date objective response criteria were first met. Gene expression profiling by HTG EdgeSeq DLBCL cell-of-origin assay was used to determine ABC and GCB subtypes.	From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.
Part 2: Number of Participants With Treatment-emergent Adverse Events	An 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 2 was 701 days.

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, 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): May 23, 2025
• Last Update Submitted That Met QC Criteria: May 7, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

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

Plan for Individual participant data (IPD)

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

IPD Plan Description

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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