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

BeiGene

Status and phase: Completed; Phase 1

Conditions: Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Treatments: Drug: Zanubrutinib; Drug: Lenalidomide

Study type: Interventional

Funder types: Industry

Identifiers

NCT04436107

BGB-3111-110

Details and patient eligibility

About

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

Enrollment: 66 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Histologically confirmed DLBCL, all participants must provide sufficient archival or fresh tumor tissue samples for evaluation by immunohistochemistry (IHC) and Gene Expression Profiling (GEP).
2. Relapsed or refractory disease, defined as either: 1) progression of disease after having achieved disease remission (complete response [CR] or partial response [PR]) , or 2) stable disease (SD), or progressive disease (PD) at completion of the treatment regimen preceding entry to the study.
3. Participants who have not received high dose therapy/stem cell transplantation (HDT/SCT) must be ineligible for HDT/SCT.
4. Measurable disease as defined by at least 1 lymph node >1.5 cm in longest diameter, or at least 1 extra-nodal lesion >1.0 cm in longest diameter, and measurable in 2 perpendicular dimensions.
5. Received an appropriate first-line therapy for DLBCL,defined as an anti CD20 antibody and an appropriate anthracycline-based combination therapy for at least 2 cycles, unless the patient is intolerant or had disease progression before Cycle 2..

Key Exclusion Criteria:

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

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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66 participants in 4 patient groups

Part 1: Zanubrutinib + Lenalidomide 15 mg

Experimental group

Description:

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.

Treatment:

Drug: Lenalidomide

Drug: Zanubrutinib

Part 1: Zanubrutinib + Lenalidomide 20 mg

Experimental group

Description:

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.

Treatment:

Drug: Lenalidomide

Drug: Zanubrutinib

Part 1: Zanubrutinib + Lenalidomide 25 mg

Experimental group

Description:

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.

Treatment:

Drug: Lenalidomide

Drug: Zanubrutinib

Part 2: Zanubrutinib + Lenalidomide 25 mg

Experimental group

Description:

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.

Treatment:

Drug: Lenalidomide

Drug: Zanubrutinib