A Study Comparing Obinutuzumab and BGB-3111 Versus Obinutuzumab Alone in Treating R/R Follicular Lymphoma (ROSEWOOD)

BeiGene

Status and phase: Completed; Phase 2

Conditions: Relapsed/Refractory Follicular Non-Hodgkin Lymphoma

Treatments: Drug: Zanubrutinib; Drug: Obinutuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03332017

2017-001552-54 (EudraCT Number)

2023-509975-17-00 (EU Trial (CTIS) Number)

BGB-3111-212

CTR20220712 (Other Identifier)

Details and patient eligibility

About

This clinical study examined the safety and efficacy of the combination of zanubrutinib and obinutuzumab versus obinutuzumab alone in adults with follicular lymphoma whose disease returned after or did not respond to prior therapy.

Full description

This study randomly assigned participants in a 2:1 ratio to receive either zanubrutinib plus obinutuzumab or obinutuzumab alone. The assignment considered how many prior treatments participants had received, whether their cancer had stopped responding to rituximab, and whether they were enrolled in Mainland China or other regions. Each treatment cycle lasted 28 days, with zanubrutinib taken by mouth twice daily and obinutuzumab given intravenously on a set schedule, followed by optional maintenance for up to 24 months. Participants who had obinutuzumab alone could have switched to the combination treatment if their disease worsened or did not respond after 12 months, if confirmed by an independent review.

Enrollment: 217 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Participants had a histologically confirmed diagnosis of B-cell follicular lymphoma.
• Participants had received two or more prior systemic treatments for follicular lymphoma.
• Participants had previously received both an anti-cluster of differentiation 20 (anti-CD20) antibody and an appropriate alkylator-based combination therapy.
• Participants had disease that had progressed after completion of the most recent therapy or was considered refractory to treatment.
• Participants had measurable disease present.
• Archival tissue confirming the diagnosis was available.
• Participants had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Participants had adequate renal and hepatic function.

Key Exclusion Criteria:

• Participants had prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor.
• Participants had known central nervous system involvement by leukemia or lymphoma.
• Participants had evidence of transformation from follicular lymphoma to another aggressive histologic subtype.
• Participants had undergone an allogeneic hematopoietic stem cell transplantation within 12 months of enrollment.
• Participants had a prior malignancy within the past 2 years, except for those who had curatively treated basal cell or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized prostate cancer with a Gleason score of 6.
• Participants had clinically significant cardiovascular disease.
• Participants had undergone major surgery within 4 weeks prior to the start of study treatment.
• Participants had an active fungal, bacterial, or viral infection requiring systemic treatment.
• Participants had a history of severe bleeding disorder.

Note: Other protocol-defined inclusion and exclusion criteria may have applied.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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217 participants in 2 patient groups

Obinutuzumab

Experimental group

Description:

Participants received obinutuzumab 1000 milligrams (mg) intravenously on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2 to 6; and then every 8 weeks for an additional 24 months or until disease progression. Each treatment cycle was 28 days. Participants who experienced progressive disease or did not respond to therapy within 12 months may have received crossover treatment with zanubrutinib + obinutuzumab at the investigator's discretion.

Treatment:

Drug: Obinutuzumab

Zanubrutinib + Obinutuzumab

Experimental group

Description:

Participants received zanubrutinib 160 mg twice a day orally with or without food and obinutuzumab 1000 mg intravenously on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2 to 6, and then every 8 weeks for an additional 24 months or until disease progression. Each treatment cycle was 28 days.

Treatment:

Drug: Obinutuzumab

Drug: Zanubrutinib