An International, Phase 2, Open-Label, Randomized Study of BGB-3111 Combined With Obinutuzumab Compared With Obinutuzumab Monotherapy in Relapsed/ Refractory Follicular Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 217
- 试验地点
- 88
- 主要终点
- Overall Response Rate (ORR) by Independent Central Review (ICR) Assessment
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Participants had adequate renal and hepatic function.
排除标准
- •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
- •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.
研究组 & 干预措施
Obinutuzumab
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.
干预措施: Obinutuzumab (Drug)
Zanubrutinib + Obinutuzumab
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.
干预措施: Zanubrutinib (Drug)
Zanubrutinib + Obinutuzumab
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.
干预措施: Obinutuzumab (Drug)
结局指标
主要结局
Overall Response Rate (ORR) by Independent Central Review (ICR) Assessment
时间窗: From first dose to primary analysis data cutoff (08OCT2021) start of a new anticancer therapy, or the crossover date, whichever came first. Median follow-up was 12.45 months.
ORR was defined as the percentage of participants who achieved a best overall response of complete response (CR) or partial response (PR) per the Lugano Classification for Non-Hodgkin's Lymphoma.
次要结局
- Overall Response Rate (ORR) as Assessed by the Investigator(From first dose to primary analysis data cutoff (08OCT2021) start of a new anticancer therapy, or the crossover date, whichever came first. Median follow-up was 12.45 months.)
- Duration of Response (DOR) as Determined by Investigator Assessment(From first dose to primary analysis data cutoff (08OCT2021) start of a new anticancer therapy, or the crossover date, whichever came first. Median follow-up was 12.45 months.)
- DOR as Determined by ICR(From first dose to primary analysis data cutoff (08OCT2021) start of a new anticancer therapy, or the crossover date, whichever came first. Median follow-up was 12.45 months.)
- Progression-free Survival (PFS)(From first dose to primary analysis data cutoff (08OCT2021) start of a new anticancer therapy, or the crossover date, whichever came first. Median follow-up was 12.45 months.)
- Overall Survival (OS)(From first dose to primary analysis data cutoff (08OCT2021) start of a new anticancer therapy, or the crossover date, whichever came first. Median follow-up was 12.45 months.)
- Complete Response Rate(From first dose to primary analysis data cutoff (08OCT2021) start of a new anticancer therapy, or the crossover date, whichever came first. Median follow-up was 12.45 months.)
- Time to Response (TTR)(From first dose to primary analysis data cutoff (08OCT2021) start of a new anticancer therapy, or the crossover date, whichever came first. Median follow-up was 12.45 months.)
- Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL), Physical Functioning, Role Functioning, and Symptom Scores(Baseline, Week 12, and Week 24)
- Change From Baseline in European Quality of Life 5-Dimensions, 5-level (EQ-5D-5L) Visual Analogue Scale (VAS)(Baseline, Week 12, and Week 24)
- Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From first dose to 30 days after zanubrutinib, 90 days after obinutuzumab, or before new therapy, whichever came first, up to study cut-off (31 Dec 2024); maximum exposure was 28.7 months for obinutuzumab and 67.4 months for combination therapy.)
- Area Under the Curve (AUCss) of Zanubrutinib at Steady State(Cycle 1 Day 1 and Cycle 2 Day 1: Predose (within 30 minutes before zanubrutinib dosing) and 2 hours (± 30 minutes) post-dose.)
- Zanubrutinib Plasma Concentrations(Cycle 1 Day 1 and Cycle 2 Day 1: Predose (within 30 minutes before zanubrutinib dosing) and 2 hours (± 30 minutes) post-dose.)
- Minimum Observed Concentration (Cmin) of Zanubrutinib at Steady State(Cycle 1 Day 1 and Cycle 2 Day 1: Predose (within 30 minutes before zanubrutinib dosing) and 2 hours (± 30 minutes) post-dose.)
- Maximum Observed Concentration (Cmax) of Zanubrutinib at Steady State(Cycle 1 Day 1 (2 hours postdose) and Cycle 2 Day 1 (predose and 2 hours postdose))