A Study of Zanubrutinib Plus Anti-CD20 Versus Lenalidomide Plus Rituximab in Participants With Relapsed/Refractory Follicular or Marginal Zone Lymphoma (MAHOGANY)

BeiGene

Status and phase: Enrolling; Phase 3

Conditions: Relapsed/Refractory Follicular Lymphoma; Marginal Zone Lymphoma

Treatments: Drug: Rituximab; Drug: Lenalidomide; Drug: Zanubrutinib; Drug: Obinutuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05100862

BGB-3111-308

CTR20232545 (Registry Identifier)

2022-502548-12-00 (Registry Identifier)

Details and patient eligibility

About

The purpose of the study is to compare the efficacy of zanubrutinib plus obinutuzumab versus lenalidomide plus rituximab (R^2) in participants with relapsed/refractory (R/R) follicular lymphoma (FL), as measured by progression-free survival as determined by an independent review committee in accordance with the 2014 modification of the International Working Group on non-Hodgkin lymphoma (NHL) Criteria based on n positron emission tomography and computed tomography (PET/CT), and to compare the efficacy of zanubrutinib plus rituximab versus R^2 in participants with R/R marginal zone lymphoma (MZL), as measured by progression free survival (PFS) assessed by IRC in accordance with CT-based Lugano 2014 Criteria.

Enrollment: 750 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Histologically confirmed grade 1-3a FL or MZL
• Previously treated with ≥ 1 line of systemic therapy including anti-CD20 agent. Must have a documented failure to achieve at least partial response during the most recent systemic therapy or documented progressive disease after the most recent systemic therapy
• Need for systemic therapy for FL or MZL
• Measurable disease by computed tomography or magnetic resonance imaging
• Adequate bone marrow, liver and renal function

Key Exclusion Criteria:

• Transformation to aggressive lymphoma
• Requiring ongoing need for corticosteroid treatment
• Clinically significant cardiovascular disease
• Prior malignancy within the past 2 years
• Active fungal, bacterial, and/or viral infection that requires systemic therapy

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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750 participants in 4 patient groups

Follicular Lymphoma Arm A: Zanubrutinib plus Obinutuzumab

Experimental group

Description:

Participants will receive zanubrutinib and Obinutuzumab. Following the completion of the combination treatment, participants will continue receiving zanubrutinib monotherapy until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or study termination, whichever occurs first.

Treatment:

Drug: Obinutuzumab

Drug: Zanubrutinib

Follicular Lymphoma Arm B: Lenalidomide plus Rituximab

Active Comparator group

Description:

Participants will receive lenalidomide and rituximab.

Treatment:

Drug: Lenalidomide

Drug: Rituximab

Marginal Zone Lymphoma Arm C: Zanubrutinib plus Rituximab

Experimental group

Description:

Participants will receive zanubrutinib and rituximab. Following the completion of the combination treatment, participants will continue receiving zanubrutinib monotherapy until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or study termination, whichever occurs first.

Treatment:

Drug: Zanubrutinib

Drug: Rituximab

Marginal Zone Lymphoma Arm D: Lenalidomide plus Rituximab

Active Comparator group

Description:

Participants will receive lenalidomide and rituximab.

Treatment:

Drug: Lenalidomide

Drug: Rituximab