Trial Outcomes & Findings for Zanubrutinib, in Combination With Lenalidomide, With or Without Rituximab in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (NCT NCT04436107)

Last Updated: 2025-05-23

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

66 participants

Primary outcome timeframe

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

Results posted on

2025-05-23

Participant Flow

This study was conducted at 10 study centers in China. Participants with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) ineligible for high-dose therapy/stem cell transplant who had received ≥ 1 prior line of systemic therapy were enrolled.

Participant milestones

Participant milestones
Measure	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.	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.	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.	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.
Overall Study STARTED	6	10	11	39
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	6	10	11	39

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.	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.
Overall Study Sponsor Ended Study	2	4	8	20
Overall Study Death	3	5	3	18
Overall Study Withdrawal by Subject	1	1	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=6 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=10 Participants 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.	Part 1: Zanubrutinib + Lenalidomide 25 mg n=11 Participants 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.	Part 2: Zanubrutinib + Lenalidomide 25 mg n=39 Participants 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.	Total n=66 Participants Total of all reporting groups
Age, Continuous	47.8 years STANDARD_DEVIATION 15.12 • n=5 Participants	54.0 years STANDARD_DEVIATION 14.83 • n=7 Participants	58.8 years STANDARD_DEVIATION 13.12 • n=5 Participants	59.1 years STANDARD_DEVIATION 11.61 • n=4 Participants	57.2 years STANDARD_DEVIATION 12.86 • n=21 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	19 Participants n=4 Participants	31 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	20 Participants n=4 Participants	35 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	10 Participants n=7 Participants	11 Participants n=5 Participants	39 Participants n=4 Participants	66 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment China	6 participants n=5 Participants	10 participants n=7 Participants	11 participants n=5 Participants	39 participants n=4 Participants	66 participants n=21 Participants

PRIMARY outcome

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

Population: The safety analysis set was defined as all participants who received at least one dose of any medication within the combination therapy.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=6 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=10 Participants 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.	Part 1: Zanubrutinib + Lenalidomide 25 mg n=11 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) TEAEs	6 Participants	10 Participants	11 Participants	—	—	—
Part 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) SAEs	0 Participants	3 Participants	4 Participants	—	—	—

PRIMARY outcome

Timeframe: 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.

Population: The efficacy analysis set was defined as all participants who were exposed to at least one dose of medication with confirmed R/R DLBCL. Participants with no post-baseline response assessments were treated as non-responders. Overall response rate was a prespecified primary endpoint in Part 2 only; results are also presented for all participants (Part 1 + Part 2) who received the recommended phase 2 dose (RP2D) of lenalidomide (25 mg).

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.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=39 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=50 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 2: Overall Response Rate (ORR)	48.7 percentage of participants Interval 32.4 to 65.2	58.0 percentage of participants Interval 43.2 to 71.8	—	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=6 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=10 Participants 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.	Part 1: Zanubrutinib + Lenalidomide 25 mg n=11 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 1: Overall Response Rate (ORR)	16.7 percentage of participants Interval 0.4 to 64.1	30.0 percentage of participants Interval 6.7 to 65.2	90.9 percentage of participants Interval 58.7 to 99.8	—	—	—

SECONDARY outcome

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

Population: The PK analysis set was defined as all participants who had at least one post-dose plasma concentration collected without a major protocol deviation affecting PK. Per the prespecified analysis of zanubrutinib PK parameters, participants were analyzed in one group since there was only one dose level for zanubrutinib, regardless of dose of lenalidomide they received. The analysis includes participants with available PK parameter data at each time point.

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.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=30 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=25 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Area Under the Plasma Concentration-time Curve From Zero to 8 Hours Postdose (AUCt) of Zanubrutinib After a Single Dose and at Steady State	847.8 h*ng/mL Geometric Coefficient of Variation 80	623.9 h*ng/mL Geometric Coefficient of Variation 49	—	—	—	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=39 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=36 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
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	798.4 h*ng/mL Geometric Coefficient of Variation 94	638.4 h*ng/mL Geometric Coefficient of Variation 57	—	—	—	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=21 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Zanubrutinib After a Single Dose	943.3 h*ng/mL Geometric Coefficient of Variation 81	—	—	—	—	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=39 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=36 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Maximum Plasma Concentration (Cmax) of Zanubrutinib After a Single Dose and at Steady State	281.2 ng/mL Geometric Coefficient of Variation 85	208.7 ng/mL Geometric Coefficient of Variation 61	—	—	—	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=39 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=36 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Time to Maximum Plasma Concentration (Tmax) of Zanubrutinib After a Single Dose and at Steady State	2.0 hours Interval 0.9 to 8.0	2.5 hours Interval 0.4 to 8.0	—	—	—	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=39 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=36 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Time to the Last Quantifiable Concentration (Tlast) of Zanubrutinib After a Single Dose and at Steady State	7.9 hours Interval 7.5 to 8.2	7.9 hours Interval 7.5 to 8.1	—	—	—	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=22 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=18 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Apparent Terminal Elimination Half-life (T1/2) of Zanubrutinib After a Single Dose and at Steady State	1.4 hours Interval 0.9 to 3.1	1.6 hours Interval 1.1 to 3.0	—	—	—	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=22 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=18 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Apparent Volume (CL/F) of Zanubrutinib After a Single Dose and at Steady State	165.9 L/h Geometric Coefficient of Variation 80	226.5 L/h Geometric Coefficient of Variation 46	—	—	—	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=22 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=18 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Apparent Clearance (Vz/F) of Zanubrutinib After a Single Dose and at Steady State	341.4 liters Geometric Coefficient of Variation 69	533.8 liters Geometric Coefficient of Variation 54	—	—	—	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=23 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Accumulation Ratio of AUCt for Zanubrutinib	0.7 ratio Geometric Coefficient of Variation 50	—	—	—	—	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=36 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Accumulation Ratio of Cmax for Zanubrutinib	0.8 ratio Geometric Coefficient of Variation 73	—	—	—	—	—

SECONDARY outcome

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

Population: The PK analysis set was defined as all participants who had at least one post-dose plasma concentration collected without a major protocol deviation affecting PK. The analysis includes participants with available PK parameter data at each time point.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=5 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=9 Participants 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.	Part 1: Zanubrutinib + Lenalidomide 25 mg n=20 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 15 mg n=2 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 Zanubrutinib + Lenalidomide 20 mg n=7 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 25 mg n=15 Participants 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.
Area Under the Plasma Concentration-time Curve From Zero to 8 Hours Postdose (AUCt) of Lenalidomide After a Single Dose and at Steady State	843.5 h*ng/mL Geometric Coefficient of Variation 51	1092.5 h*ng/mL Geometric Coefficient of Variation 59	1177.7 h*ng/mL Geometric Coefficient of Variation 125	1091.0 h*ng/mL Geometric Coefficient of Variation 34	916.1 h*ng/mL Geometric Coefficient of Variation 39	1702.6 h*ng/mL Geometric Coefficient of Variation 29

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=6 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=10 Participants 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.	Part 1: Zanubrutinib + Lenalidomide 25 mg n=23 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 15 mg n=3 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 Zanubrutinib + Lenalidomide 20 mg n=9 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 25 mg n=20 Participants 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.
AUClast of Lenalidomide After a Single Dose and at Steady State	641.9 h*ng/mL Geometric Coefficient of Variation 91	1072.7 h*ng/mL Geometric Coefficient of Variation 56	1187.4 h*ng/mL Geometric Coefficient of Variation 112	778.7 h*ng/mL Geometric Coefficient of Variation 69	824.6 h*ng/mL Geometric Coefficient of Variation 41	1389.7 h*ng/mL Geometric Coefficient of Variation 53

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=5 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=6 Participants 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.	Part 1: Zanubrutinib + Lenalidomide 25 mg n=14 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
AUCinf of Lenalidomide After a Single Dose	933.7 h*ng/mL Geometric Coefficient of Variation 52	1443.2 h*ng/mL Geometric Coefficient of Variation 29	1752.4 h*ng/mL Geometric Coefficient of Variation 28	—	—	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=6 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=10 Participants 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.	Part 1: Zanubrutinib + Lenalidomide 25 mg n=23 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 15 mg n=3 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 Zanubrutinib + Lenalidomide 20 mg n=9 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 25 mg n=20 Participants 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.
Cmax of Lenalidomide After a Single Dose and at Steady State	206.4 ng/mL Geometric Coefficient of Variation 118	276.5 ng/mL Geometric Coefficient of Variation 68	332.0 ng/mL Geometric Coefficient of Variation 123	238.5 ng/mL Geometric Coefficient of Variation 132	206.6 ng/mL Geometric Coefficient of Variation 57	372.1 ng/mL Geometric Coefficient of Variation 67

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=6 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=10 Participants 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.	Part 1: Zanubrutinib + Lenalidomide 25 mg n=23 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 15 mg n=3 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 Zanubrutinib + Lenalidomide 20 mg n=9 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 25 mg n=20 Participants 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.
Tmax of Lenalidomide After a Single Dose and at Steady State	1.5 hours Interval 0.5 to 7.6	1.5 hours Interval 0.9 to 4.3	2.0 hours Interval 0.5 to 4.1	1.9 hours Interval 0.5 to 3.8	2.1 hours Interval 0.6 to 4.0	1.9 hours Interval 0.4 to 7.9

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=6 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=10 Participants 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.	Part 1: Zanubrutinib + Lenalidomide 25 mg n=23 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 15 mg n=3 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 Zanubrutinib + Lenalidomide 20 mg n=9 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 25 mg n=20 Participants 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.
Tlast of Lenalidomide After a Single Dose and at Steady State	7.6 hours Interval 7.6 to 8.0	7.9 hours Interval 7.6 to 8.2	8.0 hours Interval 7.5 to 8.1	7.7 hours Interval 7.5 to 7.9	7.7 hours Interval 7.5 to 8.1	8.0 hours Interval 7.5 to 8.1

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=5 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=8 Participants 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.	Part 1: Zanubrutinib + Lenalidomide 25 mg n=17 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 15 mg n=2 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 Zanubrutinib + Lenalidomide 20 mg n=6 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 25 mg n=14 Participants 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.
T1/2 of Lenalidomide After a Single Dose and at Steady State	2.3 hours Interval 2.0 to 2.6	2.7 hours Interval 1.7 to 3.9	2.5 hours Interval 1.7 to 7.7	2.0 hours Interval 1.8 to 2.2	2.3 hours Interval 2.0 to 2.9	2.4 hours Interval 1.9 to 3.4

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=5 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=8 Participants 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.	Part 1: Zanubrutinib + Lenalidomide 25 mg n=17 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 15 mg n=2 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 Zanubrutinib + Lenalidomide 20 mg n=6 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 25 mg n=14 Participants 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.
CL/F of Lenalidomide After a Single Dose and at Steady State	16.1 L/h Geometric Coefficient of Variation 52	16.0 L/h Geometric Coefficient of Variation 52	13.9 L/h Geometric Coefficient of Variation 41	12.8 L/h Geometric Coefficient of Variation 35	17.6 L/h Geometric Coefficient of Variation 36	12.5 L/h Geometric Coefficient of Variation 31

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=5 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=8 Participants 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.	Part 1: Zanubrutinib + Lenalidomide 25 mg n=17 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 15 mg n=2 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 Zanubrutinib + Lenalidomide 20 mg n=6 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 25 mg n=14 Participants 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.
Vz/F of Lenalidomide After a Single Dose and at Steady State	53.6 liters Geometric Coefficient of Variation 42	62.1 liters Geometric Coefficient of Variation 76	49.7 liters Geometric Coefficient of Variation 49	37.3 liters Geometric Coefficient of Variation 19	57.6 liters Geometric Coefficient of Variation 28	43.6 liters Geometric Coefficient of Variation 20

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=2 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=6 Participants 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.	Part 1: Zanubrutinib + Lenalidomide 25 mg n=13 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Accumulation Ratio of AUCt for Lenalidomide	1.1 ratio Geometric Coefficient of Variation 48	0.8 ratio Geometric Coefficient of Variation 106	1.0 ratio Geometric Coefficient of Variation 27	—	—	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=3 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=9 Participants 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.	Part 1: Zanubrutinib + Lenalidomide 25 mg n=20 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Accumulation Ratio of Cmax for Lenalidomide	1.3 ratio Geometric Coefficient of Variation 51	0.8 ratio Geometric Coefficient of Variation 100	0.9 ratio Geometric Coefficient of Variation 59	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=3 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=3 Participants 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.	Part 1: Zanubrutinib + Lenalidomide 25 mg n=4 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 15 mg n=6 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 Zanubrutinib + Lenalidomide 20 mg n=3 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 25 mg n=8 Participants 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.
Part 1: Overall Response Rate by Immunohistochemistry Subtypes	33.3 percentage of participants Interval 0.8 to 90.6	0.0 percentage of participants Interval 0.0 to 70.8	50.0 percentage of participants Interval 6.8 to 93.2	16.7 percentage of participants Interval 0.4 to 64.1	66.7 percentage of participants Interval 9.4 to 99.2	100.0 percentage of participants Interval 63.1 to 100.0

SECONDARY outcome

Timeframe: 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.

Population: The efficacy analysis set was defined as all participants who were exposed to at least one dose of medication with confirmed R/R DLBCL. Participants with no post-baseline response assessments were treated as non-responders. Four participants in the Zanubrutinib + Lenalidomide 15 mg group had a missing or unclassified GEP-subtype and are not included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=1 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=1 Participants 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.	Part 1: Zanubrutinib + Lenalidomide 25 mg n=8 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 15 mg n=2 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 Zanubrutinib + Lenalidomide 20 mg n=9 Participants 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.	Day 21 Zanubrutinib + Lenalidomide 25 mg n=2 Participants 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.
Part 1: Overall Response Rate by Gene Expression Profiling (GEP) Subtypes	0.0 percentage of participants Interval 0.0 to 97.5	0.0 percentage of participants Interval 0.0 to 97.5	12.5 percentage of participants Interval 0.3 to 52.7	100.0 percentage of participants Interval 15.8 to 100.0	88.9 percentage of participants Interval 51.8 to 99.7	100.0 percentage of participants Interval 15.8 to 100.0

SECONDARY outcome

Timeframe: 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.

Population: The efficacy analysis set was defined as all participants who were exposed to at least one dose of medication with confirmed R/R DLBCL. Participants with no post-baseline response assessments were treated as non-responders. For Part 2 clinical outcomes analyzed by subtype, results include all participants who received the RP2D of lenalidomide (25 mg) with non-missing subtype.

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.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=16 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=34 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 2: Overall Response Rate by Immunohistochemistry Subtypes	50.0 percentage of participants Interval 24.7 to 75.3	61.8 percentage of participants Interval 43.6 to 77.8	—	—	—	—

SECONDARY outcome

Population: The efficacy analysis set was defined as all participants who were exposed to at least one dose of medication with confirmed R/R DLBCL. Participants with no post-baseline response assessments were treated as non-responders. For Part 2 clinical outcomes analyzed by subtype, results include all participants who received the RP2D of lenalidomide (25 mg) with non-missing subtype (four participants had a missing GEP-subtype and are not included).

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.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=35 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=11 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 2: Overall Response Rate by Gene Expression Profiling Subtypes	68.6 percentage of participants Interval 50.7 to 83.1	45.5 percentage of participants Interval 16.7 to 76.6	—	—	—	—

SECONDARY outcome

Population: The efficacy analysis set was defined as all participants who were exposed to at least one dose of medication with confirmed R/R DLBCL. Participants with no post-baseline response assessments were treated as non-responders. Complete response rate was a prespecified secondary endpoint in Part 2 only; results are also presented for all participants who received the RP2D of lenalidomide (25 mg).

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).

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=39 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=50 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 2: Complete Response Rate (CRR)	33.3 percentage of participants Interval 19.1 to 50.2	42.0 percentage of participants Interval 28.2 to 56.8	—	—	—	—

SECONDARY outcome

Population: The efficacy analysis set was defined as all participants who were exposed to at least one dose of medication with confirmed R/R DLBCL. Participants with no post-baseline response assessments were treated as non-responders. CRR by IHC subtype was a prespecified secondary endpoint in Part 2 only. For Part 2 clinical outcomes analyzed by subtype, results include all participants who received the RP2D of lenalidomide (25 mg) with non-missing subtype.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=16 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=34 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 2: Complete Response Rate by Immunohistochemistry Subtypes	50.0 percentage of participants Interval 24.7 to 75.3	38.2 percentage of participants Interval 22.2 to 56.4	—	—	—	—

SECONDARY outcome

Population: The efficacy analysis set was defined as all participants who were exposed to at least one dose of medication with confirmed R/R DLBCL. Participants with no post-baseline response assessments were treated as non-responders. CRR by GEP subtype was a prespecified secondary endpoint in Part 2 only. For Part 2 clinical outcomes analyzed by subtype, results include all participants who received the RP2D of lenalidomide (25 mg) with non-missing subtype.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=35 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=11 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 2: Complete Response Rate by Gene Expression Profiling Subtypes	45.7 percentage of participants Interval 28.8 to 63.4	45.5 percentage of participants Interval 16.7 to 76.6	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Population: The efficacy analysis set was defined as all participants who were exposed to at least one dose of medication with confirmed R/R DLBCL. DOR was a prespecified secondary endpoint in Part 2 only; results are also presented for all participants who received the RP2D of lenalidomide (25 mg). Participants with an overall response are included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=19 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=29 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 2: Duration of Response (DOR)	9.10 months Interval 2.79 to "NA" indicates values that could not be estimated due to insufficient number of participants with events	14.92 months Interval 5.45 to "NA" indicates values that could not be estimated due to insufficient number of participants with events	—	—	—	—

SECONDARY outcome

Timeframe: From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.

Population: The efficacy analysis set was defined as all participants who were exposed to at least one dose of medication with confirmed R/R DLBCL. DOR by IHC subtype was a prespecified secondary endpoint in Part 2 only. For Part 2 clinical outcomes analyzed by subtype, results include all participants who received the RP2D of lenalidomide (25 mg). Participants with an overall response and non-missing IHC subtype are included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=8 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=21 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 2: Duration of Response by Immunohistochemistry Subtypes	NA months Interval 2.76 to "NA" indicates values that could not be estimated due to insufficient number of participants with events	11.61 months Interval 2.83 to "NA" indicates values that could not be estimated due to insufficient number of participants with events	—	—	—	—

SECONDARY outcome

Timeframe: From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.

Population: The efficacy analysis set was defined as all participants who were exposed to at least one dose of medication with confirmed R/R DLBCL. DOR by GEP subtype was a prespecified secondary endpoint in Part 2 only. For Part 2 clinical outcomes analyzed by subtype, results include all participants who received the RP2D of lenalidomide (25 mg). Participants with an overall response and non-missing GEP subtype are included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=24 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=5 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 2: Duration of Response by Gene Expression Profiling Subtypes	15.67 months Interval 3.02 to "NA" indicates values that could not be estimated due to insufficient number of participants with events	9.10 months Interval 3.02 to "NA" indicates values that could not be estimated due to insufficient number of participants with events	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Population: The efficacy analysis set was defined as all participants who were exposed to at least one dose of medication with confirmed R/R DLBCL. PFS was a prespecified secondary endpoint in Part 2 only; results are also presented for all participants who received the RP2D of lenalidomide.

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.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=39 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=50 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 2: Progression-free Survival (PFS)	4.76 months Interval 2.73 to 8.94	5.52 months Interval 2.86 to 11.07	—	—	—	—

SECONDARY outcome

Timeframe: From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.

Population: The efficacy analysis set was defined as all participants who were exposed to at least one dose of medication with confirmed R/R DLBCL. PFS by IHC subtype was a prespecified secondary endpoint in Part 2 only. For Part 2 clinical outcomes analyzed by subtype, results include all participants who received the RP2D of lenalidomide (25 mg) with non-missing subtype.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=16 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=34 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 2: Progression-Free Survival by Immunohistochemistry Subtypes	5.55 months Interval 1.61 to "NA" indicates values that could not be estimated due to insufficient number of participants with events	5.52 months Interval 2.86 to 11.04	—	—	—	—

SECONDARY outcome

Timeframe: From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.

Population: The efficacy analysis set was defined as all participants who were exposed to at least one dose of medication with confirmed R/R DLBCL. PFS by GEP subtype was a prespecified secondary endpoint in Part 2 only. For Part 2 clinical outcomes analyzed by subtype, results include all participants who received the RP2D of lenalidomide (25 mg) with non-missing subtype (four participants had a missing GEP-subtype and are not included).

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=35 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=11 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 2: Progression-Free Survival by Gene Expression Profiling Subtypes	5.55 months Interval 4.76 to 18.4	5.40 months Interval 1.41 to 14.65	—	—	—	—

SECONDARY outcome

Population: The efficacy analysis set was defined as all participants who were exposed to at least one dose of medication with confirmed R/R DLBCL. TTR was a prespecified secondary endpoint in Part 2 only; results are also presented for all participants who received the RP2D of lenalidomide (25 mg). Participants with an overall response are included in the analysis.

Time to response is defined as time from the starting date of combination therapy to the date the response criteria were first met.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=19 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=29 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 2: Time to Response (TTR)	2.76 months Interval 2.73 to 2.89	2.76 months Interval 2.73 to 2.83	—	—	—	—

SECONDARY outcome

Population: The efficacy analysis set was defined as all participants who were exposed to at least one dose of medication with confirmed R/R DLBCL. TTR by IHC subtype was a prespecified secondary endpoint in Part 2 only. For Part 2 clinical outcomes analyzed by subtype, results include all participants who received the RP2D of lenalidomide (25 mg). Participants with an overall response and non-missing IHC subtype are included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=8 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=21 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 2: Time to Response by Immunohistochemistry Subtypes	2.87 months Interval 2.78 to 3.33	2.76 months Interval 2.73 to 2.79	—	—	—	—

SECONDARY outcome

Timeframe: From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.

Population: The efficacy analysis set was defined as all participants who were exposed to at least one dose of medication with confirmed R/R DLBCL. TTR by GEP subtype was a prespecified secondary endpoint in Part 2 only. For Part 2 clinical outcomes analyzed by subtype, results include all participants who received the RP2D of lenalidomide (25 mg). Participants with an overall response and non-missing GEP subtype are included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=24 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Part 1: Zanubrutinib + Lenalidomide 20 mg n=5 Participants 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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 2: Time to Response by Gene Expression Profiling Subtypes	2.76 months Interval 2.73 to 2.83	3.19 months Interval 2.79 to 3.48	—	—	—	—

SECONDARY outcome

Timeframe: From first dose of study drug to 30 days after last dose. Maximum time on treatment in Part 2 was 701 days.

Population: The safety analysis set was defined as all participants who received at least one dose of any medication within the combination therapy.

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).

Outcome measures

Outcome measures
Measure	Part 1: Zanubrutinib + Lenalidomide 15 mg n=39 Participants Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	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.	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.	Day 21 Zanubrutinib + Lenalidomide 15 mg Participants received zanubrutinib 160 mg orally BID and lenalidomide 15 mg orally QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity.	Day 21 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.	Day 21 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.
Part 2: Number of Participants With Treatment-emergent Adverse Events TEAEs	39 Participants	—	—	—	—	—
Part 2: Number of Participants With Treatment-emergent Adverse Events SAEs	14 Participants	—	—	—	—	—

Adverse Events

Part 1: Zanubrutinib + Lenalidomide 15 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 3 deaths

Part 1: Zanubrutinib + Lenalidomide 20 mg

Serious events: 3 serious events

Other events: 10 other events

Deaths: 5 deaths

Part 1: Zanubrutinib + Lenalidomide 25 mg

Serious events: 4 serious events

Other events: 11 other events

Deaths: 3 deaths

Part 2: Zanubrutinib + Lenalidomide 25 mg

Serious events: 14 serious events

Other events: 39 other events

Deaths: 18 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

BeiGene

Phone: 1 877-828-5568

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period,Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information \& may request a further delay to protect its IP rights.
Publication restrictions are in place

Restriction type: OTHER