Phase 1
N=66
Zanubrutinib, in Combination With Lenalidomide, With or Without Rituximab in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT04436107 ↗Enrolled (actual)
66
Serious AEs
31.8%
Results posted
May 2025
Primary outcome: Primary: Part 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) — 6; 10; 11; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Zanubrutinib (Drug); Lenalidomide (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- BeiGene
- Primary completion
- Mar 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) |
6; 10; 11; 0; 3; 4 | — |
| PRIMARY Part 2: Overall Response Rate (ORR) |
48.7; 58.0 | — |
| SECONDARY Part 1: Overall Response Rate (ORR) |
16.7; 30.0; 90.9 | — |
| SECONDARY 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; 623.9 | — |
| SECONDARY 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; 638.4 | — |
| SECONDARY Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Zanubrutinib After a Single Dose |
943.3 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Zanubrutinib After a Single Dose and at Steady State |
281.2; 208.7 | — |
| SECONDARY Time to Maximum Plasma Concentration (Tmax) of Zanubrutinib After a Single Dose and at Steady State |
2.0; 2.5 | — |
| SECONDARY Time to the Last Quantifiable Concentration (Tlast) of Zanubrutinib After a Single Dose and at Steady State |
7.9; 7.9 | — |
| SECONDARY Apparent Terminal Elimination Half-life (T1/2) of Zanubrutinib After a Single Dose and at Steady State |
1.4; 1.6 | — |
| SECONDARY Apparent Volume (CL/F) of Zanubrutinib After a Single Dose and at Steady State |
165.9; 226.5 | — |
| SECONDARY Apparent Clearance (Vz/F) of Zanubrutinib After a Single Dose and at Steady State |
341.4; 533.8 | — |
| SECONDARY Accumulation Ratio of AUCt for Zanubrutinib |
0.7 | — |
| SECONDARY Accumulation Ratio of Cmax for Zanubrutinib |
0.8 | — |
| SECONDARY 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; 1092.5; 1177.7; 1091.0; 916.1; 1702.6 | — |
| SECONDARY AUClast of Lenalidomide After a Single Dose and at Steady State |
641.9; 1072.7; 1187.4; 778.7; 824.6; 1389.7 | — |
| SECONDARY AUCinf of Lenalidomide After a Single Dose |
933.7; 1443.2; 1752.4 | — |
| SECONDARY Cmax of Lenalidomide After a Single Dose and at Steady State |
206.4; 276.5; 332.0; 238.5; 206.6; 372.1 | — |
| SECONDARY Tmax of Lenalidomide After a Single Dose and at Steady State |
1.5; 1.5; 2.0; 1.9; 2.1; 1.9 | — |
| SECONDARY Tlast of Lenalidomide After a Single Dose and at Steady State |
7.6; 7.9; 8.0; 7.7; 7.7; 8.0 | — |
| SECONDARY T1/2 of Lenalidomide After a Single Dose and at Steady State |
2.3; 2.7; 2.5; 2.0; 2.3; 2.4 | — |
| SECONDARY CL/F of Lenalidomide After a Single Dose and at Steady State |
16.1; 16.0; 13.9; 12.8; 17.6; 12.5 | — |
| SECONDARY Vz/F of Lenalidomide After a Single Dose and at Steady State |
53.6; 62.1; 49.7; 37.3; 57.6; 43.6 | — |
| SECONDARY Accumulation Ratio of AUCt for Lenalidomide |
1.1; 0.8; 1.0 | — |
| SECONDARY Accumulation Ratio of Cmax for Lenalidomide |
1.3; 0.8; 0.9 | — |
| SECONDARY Part 1: Overall Response Rate by Immunohistochemistry Subtypes |
33.3; 0.0; 50.0; 16.7; 66.7; 100.0 | — |
| SECONDARY Part 1: Overall Response Rate by Gene Expression Profiling (GEP) Subtypes |
0.0; 0.0; 12.5; 100.0; 88.9; 100.0 | — |
| SECONDARY Part 2: Overall Response Rate by Immunohistochemistry Subtypes |
50.0; 61.8 | — |
| SECONDARY Part 2: Overall Response Rate by Gene Expression Profiling Subtypes |
68.6; 45.5 | — |
| SECONDARY Part 2: Complete Response Rate (CRR) |
33.3; 42.0 | — |
| SECONDARY Part 2: Complete Response Rate by Immunohistochemistry Subtypes |
50.0; 38.2 | — |
| SECONDARY Part 2: Complete Response Rate by Gene Expression Profiling Subtypes |
45.7; 45.5 | — |
| SECONDARY Part 2: Duration of Response (DOR) |
9.10; 14.92 | — |
| SECONDARY Part 2: Duration of Response by Immunohistochemistry Subtypes |
NA; 11.61 | — |
| SECONDARY Part 2: Duration of Response by Gene Expression Profiling Subtypes |
15.67; 9.10 | — |
| SECONDARY Part 2: Progression-free Survival (PFS) |
4.76; 5.52 | — |
| SECONDARY Part 2: Progression-Free Survival by Immunohistochemistry Subtypes |
5.55; 5.52 | — |
| SECONDARY Part 2: Progression-Free Survival by Gene Expression Profiling Subtypes |
5.55; 5.40 | — |
| SECONDARY Part 2: Time to Response (TTR) |
2.76; 2.76 | — |
| SECONDARY Part 2: Time to Response by Immunohistochemistry Subtypes |
2.87; 2.76 | — |
| SECONDARY Part 2: Time to Response by Gene Expression Profiling Subtypes |
2.76; 3.19 | — |
| SECONDARY Part 2: Number of Participants With Treatment-emergent Adverse Events |
39; 14 | — |
Summary
The primary objective of this study is to determine the maximum tolerated doses (MTD) and the recommended Phase 2 dose (RP2D), and safety, tolerability, and efficacy of zanubrutinib in combination with lenalidomide in participants with R/R DLBCL
Eligibility Criteria
Key Inclusion Criteria
- Histologically confirmed DLBCL, all participants must provide sufficient archival or fresh tumor tissue samples for evaluation by immunohistochemistry (IHC) and Gene Expression Profiling (GEP).
- Relapsed or refractory disease, defined as either: 1) progression of disease after having achieved disease remission (complete response [CR] or partial response [PR]) , or 2) stable disease (SD), or progressive disease (PD) at completion of the treatment regimen preceding entry to the study.
- Participants who have not received high dose therapy/stem cell transplantation (HDT/SCT) must be ineligible for HDT/SCT.
- Measurable disease as defined by at least 1 lymph node >1.5 cm in longest diameter, or at least 1 extra-nodal lesion >1.0 cm in longest diameter, and measurable in 2 perpendicular dimensions.
- Received an appropriate first-line therapy for DLBCL,defined as an anti CD20 antibody and an appropriate anthracycline-based combination therapy for at least 2 cycles, unless the patient is intolerant or had disease progression before Cycle 2..
Key Exclusion Criteria
- Current or history of central nervous system (CNS) lymphoma.
- Histologically transformed lymphoma.
- History of allogeneic stem-cell transplantation.
- Prior exposure to a BTK inhibitor.
- Prior exposure to lenalidomide or thalidomide.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT04436107). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.