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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
217
Oral administration as a capsule
Intravenous administration
Overall Response Rate (ORR) by Independent Central Review (ICR) Assessment
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.
Time frame: 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 Response Rate (ORR) as Assessed by the Investigator
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.
Time frame: 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
DOR was defined as the time from the date that a confirmed response (CR or PR) was first observed to the date of first documented disease progression or death, whichever occurred first. For participants in the monotherapy arm who crossed over to combination therapy, disease assessments after crossover were not included in the DOR calculation. Median DOR was estimated using the Kaplan-Meier method.
Time frame: 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
DOR was defined as the time from the date that a confirmed response (CR or PR) was first observed to the date of first documented disease progression or death, whichever occurred first. For participants in the monotherapy arm who crossed over to combination therapy, disease assessments after crossover were not included in the DOR calculation. Median DOR was estimated using the Kaplan-Meier method.
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Emory University Winship Cancer Institute
Atlanta, Georgia, United States
University of Illinois At Chicago
Chicago, Illinois, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States
Duke University
Durham, North Carolina, United States
Canberra Hospital
Garran, Australian Capital Territory, Australia
Concord Repatriation General Hospital
Concord, New South Wales, Australia
Saint Vincents Hospital Sydney
Darlinghurst, New South Wales, Australia
Calvary Mater Newcastle
Waratah, New South Wales, Australia
Westmead Hospital
Westmead, New South Wales, Australia
Icon Cancer Centre Wesley
Auchenflower, Queensland, Australia
...and 78 more locations
Time frame: 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)
PFS was defined as the time from randomization to the date of first documented disease progression or death from any cause, whichever occurred first, as determined by the ICR or investigator assessment. For participants in the monotherapy arm who crossed over to combination therapy, disease assessments after crossover were not included in the PFS calculation. Median PFS was estimated using the Kaplan-Meier method.
Time frame: 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)
OS was defined as the time from randomization to the date of death from any cause. Median OS was estimated using the Kaplan-Meier method.
Time frame: 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
CRR was defined as the percentage of participants who achieved a complete response or complete metabolic response as their best overall response, as determined by ICR and investigator assessment. Responses were assessed from randomization until the data cutoff date, the start of a new anticancer therapy, or the crossover date for participants in the monotherapy arm who switched to combination therapy.
Time frame: 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)
TRR was defined as the time from randomization to the first date that response criteria (CR or PR) were met, as determined by ICR and investigator assessment. Only participants who achieved an overall response were included in the analysis. For participants in the monotherapy arm who crossed over to combination therapy, disease assessments after crossover were not included in the TRR calculation.
Time frame: 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
The EORTC QLQ-C30 includes 30 questions covering 5 functional scales (physical, role, emotional, cognitive, social), 1 global health scale, 3 symptom scales (fatigue, nausea/vomiting, pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties). Participants report their health over the past week. Most items use a 4-point scale (1 = Not at all to 4 = Very much), while 2 global QOL items use a 7-point scale (1 = Very poor to 7 = Excellent). Raw scores are linearly transformed to a 0-100 scale; higher GHS and functional scores and lower symptom scores indicate better quality of life.
Time frame: 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)
The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes.
Time frame: Baseline, Week 12, and Week 24
Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event refers to any unintended or unfavorable sign, symptom, or condition (including abnormal lab results) that occurs during the study, regardless of whether it is linked to the study drug.
Time frame: 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
Pharmacokinetic exposure parameters were estimated for each participant using a population pharmacokinetic (PK) model.
Time frame: 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
Time frame: 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
Pharmacokinetic exposure parameters were estimated for each participant using a population pharmacokinetic (PK) model.
Time frame: 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
Time frame: Cycle 1 Day 1 (2 hours postdose) and Cycle 2 Day 1 (predose and 2 hours postdose)