The primary objective of this study is to determine the maximum tolerated doses (MTD) and the recommended Phase 2 dose (RP2D), and safety, tolerability, and efficacy of zanubrutinib in combination with lenalidomide in participants with R/R DLBCL
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
66
160 mg administered orally twice daily (BID)
Administered orally on Days 1-21 each cycle followed by a mandatory 7-day drug-free interval.
Beijing Friendship Hospital, Capital Medical University
Beijing, Beijing Municipality, China
Sun Yat Sen University Cancer Center
Guangzhou, Guangdong, China
Henan Cancer Hospital
Zhengzhou, Henan, China
Part 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is defined as any untoward medical occurrence in a patient temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with lenalidomide). A serious adverse event (SAE) is any untoward medical occurrence that, at any dose: * Resulted in death. * Was life threatening. * Required hospitalization or prolongation of existing hospitalization. * Resulted in disability/incapacity. * Was a congenital anomaly/birth defect. * Was considered a significant medical AE by the investigator based on medical judgement (eg, may have jeopardized the patient or may have required medical/surgical intervention to prevent one of the outcomes listed above).
Time frame: From first dose of study drug to 30 days after last dose. Maximum time on treatment in Part 1 was 1260 days.
Part 2: Overall Response Rate (ORR)
ORR is defined as the percentage of participants who achieved a best overall response of partial response (PR) or complete response (CR) based on the Lugano classification as assessed by the investigator. Response was evaluated using computed tomography (CT) and metabolic imaging (fluorodeoxyglucose-positron emission tomography (FDG-PET)). CR: complete metabolic (no/minimal FDG uptake and no evidence of FDG-avid disease in bone marrow) and radiologic response (target lesions regressed to ≤ 1.5 cm in longest diameter with no extra-lymphatic sites of disease, no organ enlargement and normal bone marrow morphology), no new lesions, and no bone marrow involvement confirmed by bone marrow biopsies (if bone marrow was involved at baseline). PR is partial metabolic (reduced FDG uptake from Baseline) and radiologic response (≥ 50% decrease in size of measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by \> 50% in length beyond normal) and no new lesions.
Time frame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up was 24 months in Part 2 and 31 months in the RP2D group.
Part 1: Overall Response Rate (ORR)
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Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
Jilin Cancer Hospital
Changchun, Jilin, China
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
Shanghai East Hospital
Shanghai, Shanghai Municipality, China
West China Hospital, Sichuan University
Chengdu, Sichuan, China
Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality, China
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, China
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.
Time frame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up in Part 1 was 42 months.
Area Under the Plasma Concentration-time Curve From Zero to 8 Hours Postdose (AUCt) of Zanubrutinib After a Single Dose and at Steady State
Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation (LLOQ) was 1.00 ng/mL.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Zanubrutinib After a Single Dose and at Steady State
Blood samples to characterize the PK profile of zanubrutinib and lenalidomide when given in combination were collected after first dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 1.00 ng/mL.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Zanubrutinib After a Single Dose
Blood samples to characterize the PK profile of zanubrutinib and lenalidomide when given in combination were collected after first dose (Cycle 1 Day 1) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 1.00 ng/mL.
Time frame: Cycle 1 Day 1, 0.5, 1, 2, 3, 4, and 8 hours postdose
Maximum Plasma Concentration (Cmax) of Zanubrutinib After a Single Dose and at Steady State
Blood samples to characterize the PK profile of zanubrutinib and lenalidomide when given in combination were collected after first dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 1.00 ng/mL.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Time to Maximum Plasma Concentration (Tmax) of Zanubrutinib After a Single Dose and at Steady State
Blood samples to characterize the PK profile of zanubrutinib and lenalidomide when given in combination were collected after first dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 1.00 ng/mL.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Time to the Last Quantifiable Concentration (Tlast) of Zanubrutinib After a Single Dose and at Steady State
Blood samples to characterize the PK profile of zanubrutinib and lenalidomide when given in combination were collected after first dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 1.00 ng/mL.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Apparent Terminal Elimination Half-life (T1/2) of Zanubrutinib After a Single Dose and at Steady State
Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation (LLOQ) was 1.00 ng/mL.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Apparent Volume (CL/F) of Zanubrutinib After a Single Dose and at Steady State
Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation (LLOQ) was 1.00 ng/mL.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Apparent Clearance (Vz/F) of Zanubrutinib After a Single Dose and at Steady State
Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation (LLOQ) was 1.00 ng/mL.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Accumulation Ratio of AUCt for Zanubrutinib
Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation (LLOQ) was 1.00 ng/mL. Accumulation ratio is defined as the ratio of AUCt at steady state (Day 21) to the AUCt after the first dose (Day 1).
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Accumulation Ratio of Cmax for Zanubrutinib
Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation (LLOQ) was 1.00 ng/mL. Accumulation ratio is defined as the ratio of Cmax at steady state (Day 21) to the Cmax after the first dose (Day 1).
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Area Under the Plasma Concentration-time Curve From Zero to 8 Hours Postdose (AUCt) of Lenalidomide After a Single Dose and at Steady State
Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
AUClast of Lenalidomide After a Single Dose and at Steady State
Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
AUCinf of Lenalidomide After a Single Dose
Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.
Time frame: Cycle 1 Day 1 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Cmax of Lenalidomide After a Single Dose and at Steady State
Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Tmax of Lenalidomide After a Single Dose and at Steady State
Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Tlast of Lenalidomide After a Single Dose and at Steady State
Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
T1/2 of Lenalidomide After a Single Dose and at Steady State
Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
CL/F of Lenalidomide After a Single Dose and at Steady State
Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Vz/F of Lenalidomide After a Single Dose and at Steady State
Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Accumulation Ratio of AUCt for Lenalidomide
Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL. Accumulation ratio is defined as the ratio of AUCt at steady state (Day 21) to AUCt after the first dose (Day 1).
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Accumulation Ratio of Cmax for Lenalidomide
Blood samples to characterize the pharmacokinetic (PK) profile of zanubrutinib and lenalidomide when given in combination were collected after a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21) for participants in Part 1 and for twelve participants from the first stage of enrollment in Part 2. The lower limit of quantitation was 2.00 ng/mL. Accumulation ratio is defined as the ratio of Cmax at steady state (Day 21) to Cmax after the first dose (Day 1).
Time frame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
Part 1: Overall Response Rate by Immunohistochemistry Subtypes
ORR is defined as the percentage of participants who achieved a best overall response of PR or CR based on the Lugano classification as assessed by the investigator. Response was evaluated using CT and metabolic imaging (FDG-PET). CR: complete metabolic (no/minimal FDG uptake and no evidence of FDG-avid disease in bone marrow) and radiologic response (target lesions regressed to ≤ 1.5 cm in longest diameter with no extra-lymphatic sites of disease, no organ enlargement and normal bone marrow morphology), no new lesions, and no bone marrow involvement confirmed by bone marrow biopsies (if bone marrow was involved at baseline). PR is partial metabolic (reduced FDG uptake from Baseline) and radiologic response (≥ 50% decrease in size of measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by \> 50% in length beyond normal) and no new lesions. Immunohistochemistry (IHC) was used to identify germinal B-cell-like (GCB) and non-GCB phenotypes.
Time frame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up in Part 1 was 42 months.
Part 1: Overall Response Rate by Gene Expression Profiling (GEP) Subtypes
The percentage of participants who achieved a best overall response of PR or CR based on the Lugano classification as assessed by the investigator. Response was evaluated using CT and metabolic imaging. CR: complete metabolic (no/minimal FDG uptake and no evidence of FDG-avid disease in bone marrow) and radiologic response (target lesions regressed to ≤ 1.5 cm in longest diameter with no extra-lymphatic sites of disease, no organ enlargement and normal bone marrow morphology), no new lesions, and no bone marrow involvement confirmed by bone marrow biopsies (if bone marrow was involved at baseline). PR: partial metabolic (reduced FDG uptake from Baseline) and radiologic response (≥ 50% decrease in size of measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by \> 50% in length beyond normal) and no new lesions. Gene expression profiling by HTG EdgeSeq DLBCL cell-of-origin (COO) assay was used to determine activated B-cell like (ABC) and GCB subtypes.
Time frame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up in Part 1 was 42 months.
Part 2: Overall Response Rate by Immunohistochemistry Subtypes
ORR is defined as the percentage of participants who achieved a best overall response of PR or CR based on the Lugano classification as assessed by the investigator. CR: complete metabolic (no/minimal FDG uptake and no evidence of FDG-avid disease in bone marrow) and radiologic response (target lesions regressed to ≤ 1.5 cm in longest diameter with no extra-lymphatic sites of disease, no organ enlargement and normal bone marrow morphology), no new lesions, and no bone marrow involvement confirmed by bone marrow biopsy (if bone marrow was involved at baseline). PR: partial metabolic (reduced FDG uptake from Baseline) and radiologic response (≥ 50% decrease in size of measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by \> 50% in length beyond normal) and no new lesions. Immunohistochemistry was used to identify GCB and non-GCB phenotypes.
Time frame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up was 31 months in the RP2D group.
Part 2: Overall Response Rate by Gene Expression Profiling Subtypes
ORR is defined as the percentage of participants who achieved a best overall response of PR or CR based on the Lugano classification assessed by the investigator. CR: complete metabolic (no/minimal FDG uptake and no evidence of FDG-avid disease in bone marrow) and radiologic response (target lesions regressed to ≤1.5 cm in longest diameter with no extra-lymphatic sites of disease, no organ enlargement and normal bone marrow morphology), no new lesions, and no bone marrow involvement confirmed by bone marrow biopsy (if bone marrow was involved at baseline). PR: partial metabolic (reduced FDG uptake from Baseline) and radiologic response (≥ 50% decrease in size of measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by \> 50% in length beyond normal) and no new lesions. Gene expression profiling by HTG EdgeSeq DLBCL COO assay was used to determine ABC and GCB subtypes.
Time frame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up was 31 months in the RP2D group.
Part 2: Complete Response Rate (CRR)
CRR is defined as the percentage of participants who achieved a best overall response of complete response (CR) based on the Lugano classification as assessed by the investigator. Response was evaluated using CT and metabolic imaging (FDG-PET). CR: complete metabolic (no/minimal FDG uptake and no evidence of FDG-avid disease in bone marrow) and radiologic response (target lesions regressed to ≤1.5 cm in longest diameter with no extra-lymphatic sites of disease, no organ enlargement and normal bone marrow morphology), no new lesions, and no bone marrow involvement confirmed by bone marrow biopsies (if bone marrow was involved at baseline).
Time frame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up was 24 months in Part 2 and 31 months in the RP2D group.
Part 2: Complete Response Rate by Immunohistochemistry Subtypes
CRR is defined as the percentage of participants who achieved a best overall response of complete response (CR) based on the Lugano classification as assessed by the investigator. Response was evaluated using CT and metabolic imaging (FDG-PET). CR: complete metabolic (no/minimal FDG uptake and no evidence of FDG-avid disease in bone marrow) and radiologic response (target lesions regressed to ≤1.5 cm in longest diameter with no extra-lymphatic sites of disease, no organ enlargement and normal bone marrow morphology), no new lesions, and no bone marrow involvement confirmed by bone marrow biopsies (if bone marrow was involved at baseline). Immunohistochemistry was used to identify GCB and non-GCB phenotypes.
Time frame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up was 31 months in the RP2D group.
Part 2: Complete Response Rate by Gene Expression Profiling Subtypes
CRR is defined as the percentage of participants who achieved a best overall response of complete response (CR) based on the Lugano classification as assessed by the investigator. Response was evaluated using CT and metabolic imaging (FDG-PET). CR: complete metabolic (no/minimal FDG uptake and no evidence of FDG-avid disease in bone marrow) and radiologic response (target lesions regressed to ≤1.5 cm in longest diameter with no extra-lymphatic sites of disease, no organ enlargement and normal bone marrow morphology), no new lesions, and no bone marrow involvement confirmed by bone marrow biopsies (if bone marrow was involved at baseline). Gene expression profiling by HTG EdgeSeq DLBCL cell-of-origin assay was used to determine ABC and GCB subtypes.
Time frame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up was 31 months in the RP2D group.
Part 2: Duration of Response (DOR)
DOR is defined as the time from the date that the response criteria were first met to the date that progressive disease (PD) was objectively documented or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method. Participants who did not have disease progression were censored at their last valid assessment. PD: Progressive metabolic disease (increased FDG uptake from Baseline and/or new FDG-avid foci consistent with lymphoma), abnormal node or lesions with longest diameter \> 1.5 cm, an increase of ≥ 50% in the product of the perpendicular diameters, and an increase in the longest diameter of 0.5 cm for lesions ≤ 2 cm or 1.0 cm for lesions \> 2 cm, or any new lesions.
Time frame: From first dose to the end of study; maximum time on follow-up was 24 months in Part 2 and 31 months in the RP2D group.
Part 2: Duration of Response by Immunohistochemistry Subtypes
DOR is defined as the time from the date that the response criteria were first met to the date that progressive disease PD was objectively documented or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method. Participants who did not have disease progression were censored at their last valid assessment. Immunohistochemistry was used to identify GCB and non-GCB phenotypes.
Time frame: From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.
Part 2: Duration of Response by Gene Expression Profiling Subtypes
DOR is defined as the time from the date that the response criteria were first met to the date that progressive disease PD was objectively documented or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method. Participants who did not have disease progression were censored at their last valid assessment. Gene expression profiling by HTG EdgeSeq DLBCL cell-of-origin assay was used to determine ABC and GCB subtypes.
Time frame: From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.
Part 2: Progression-free Survival (PFS)
PFS is defined as the time from the starting date of the combination therapy to the date of first documentation of disease progression or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Participants who did not have disease progression were censored at their last valid tumor assessment.
Time frame: From first dose to the end of study; maximum time on follow-up was 24 months in Part 2 and 31 months in the RP2D group.
Part 2: Progression-Free Survival by Immunohistochemistry Subtypes
PFS is defined as the time from the starting date of the combination therapy to the date of first documentation of disease progression or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Participants who did not have disease progression were censored at their last valid tumor assessment. Immunohistochemistry was used to identify GCB and non-GCB phenotypes.
Time frame: From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.
Part 2: Progression-Free Survival by Gene Expression Profiling Subtypes
PFS is defined as the time from the starting date of the combination therapy to the date of first documentation of disease progression or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Participants who did not have disease progression were censored at their last valid tumor assessment. Gene expression profiling by HTG EdgeSeq DLBCL cell-of-origin assay was used to determine ABC and GCB subtypes.
Time frame: From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.
Part 2: Time to Response (TTR)
Time to response is defined as time from the starting date of combination therapy to the date the response criteria were first met.
Time frame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up was 24 months in Part 2 and 31 months in the RP2D group.
Part 2: Time to Response by Immunohistochemistry Subtypes
Time to response is defined as time from the starting date of combination therapy to the date the response criteria were first met. Immunohistochemistry was used to identify GCB and non-GCB phenotypes.
Time frame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up was 31 months in the RP2D group.
Part 2: Time to Response by Gene Expression Profiling Subtypes
Time to response is defined as the time from the starting date of combination therapy to the date objective response criteria were first met. Gene expression profiling by HTG EdgeSeq DLBCL cell-of-origin assay was used to determine ABC and GCB subtypes.
Time frame: From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.
Part 2: Number of Participants With Treatment-emergent Adverse Events
An AE is defined as any untoward medical occurrence in a patient temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with lenalidomide). A serious adverse event (SAE) is any untoward medical occurrence that, at any dose: * Resulted in death. * Was life threatening. * Required hospitalization or prolongation of existing hospitalization. * Resulted in disability/incapacity. * Was a congenital anomaly/birth defect. * Was considered a significant medical AE by the investigator based on medical judgement (eg, may have jeopardized the patient or may have required medical/surgical intervention to prevent one of the outcomes listed above).
Time frame: From first dose of study drug to 30 days after last dose. Maximum time on treatment in Part 2 was 701 days.