A Study to Investigate the Efficacy and Safety of Sonrotoclax Plus Zanubrutinib Compared With Placebo Plus Zanubrutinib in Adults With Relapsed/Refractory Mantle Cell Lymphoma

Phase 3

Recruiting

• Conditions: Mantle Cell Lymphoma; B Cell Lymphoma
• Interventions: Drug: Sonrotoclax; Drug: Zanubrutinib; Drug: Placebo

• Registration Number: NCT06742996
• Lead Sponsor: BeiGene

Brief Summary

The goal of this study is to compare how well sonrotoclax plus zanubrutinib works versus zanubrutinib plus placebo in treating adults with relapsed/refractory (R/R) mantle cell lymphoma (MCL). This study will also look at the safety of sonrotoclax plus zanubrutinib versus zanubrutinib plus placebo.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-12-16
• Study First Submitted QC: 2024-12-16
• Study First Posted: 2024-12-19
• Study Start: 2025-03-05
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-20
• Last Update Posted: 2025-06-22
• Primary Completion: 2029-03-31
• Study Completion: 2032-10-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Histologically confirmed diagnosis of MCL based on the World Health Organization 2022 classification of Haematolymphoid Tumors (WHO-HAEM5), or based on International Consensus Classification (ICC)
• Received 1 to 5 prior lines of systemic therapy including an anti-CD20 monoclonal antibody (mAb)-based immunotherapy or chemoimmunotherapy and requiring treatment in the opinion of the investigator
• Relapsed or refractory disease after the last line of therapy
• Measurable disease defined as ≥ 1 nodal lesion that is > 1.5 cm in longest diameter, or ≥ 1 extranodal lesion that is > 1 cm in longest diameter
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
• Adequate organ function

Exclusion Criteria

• Prior therapy with B-cell lymphoma-2 inhibitor
• Prior therapy with covalent or non-covalent Bruton tyrosine kinase inhibitor (BTKi) unless the participant was intolerant of non-zanubrutinib covalent or non-covalent BTKi
• Prior autologous stem cell transplantation or chimeric antigen receptor T-cell therapy within 3 months before first dose of study drug
• Prior allogeneic stem cell transplant within 6 months of the first dose of the study drug
• Known central nervous system involvement by lymphoma
• Clinically significant cardiovascular disease
• History of stroke or intracranial hemorrhage within 6 months before first dose of study drug

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: sonrotoclax plus zanubrutinib	Sonrotoclax	Sonrotoclax and zanubrutinib will be administered in combination.
Arm A: sonrotoclax plus zanubrutinib	Zanubrutinib	Sonrotoclax and zanubrutinib will be administered in combination.
Arm B: placebo plus zanubrutinib	Zanubrutinib	Placebo and zanubrutinib will be administered in combination.
Arm B: placebo plus zanubrutinib	Placebo	Placebo and zanubrutinib will be administered in combination.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) as assessed by Blinded Independent Review Committee (BIRC)	Approximately 49 months	PFS is defined as the time from randomization to the date of progression or death, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR) as assessed by BIRC and by INV	Approximately 66 months	ORR is defined as the percentage of participants who achieved a best overall response of partial response (PR) or complete response (CR), per Lugano 2014 criteria.
Overall Survival (OS)	Approximately 92 months	OS is defined as the time from randomization to the date of death from any cause.
PFS as assessed by investigator (INV)	Approximately 66 months	PFS is defined as the time from randomization to the date of progression or death, whichever occurs first.
Duration of Response (DOR) as assessed by BIRC and by INV	Approximately 66 months	DOR is defined as the time from the first qualifying response to the date of progression or death, whichever occurs first.
Complete Response Rate (CRR) as assessed by BIRC and by INV	Approximately 66 months	CRR is defined as the percentage of participants who achieved a best overall response of CR.
Time to first response as assessed by BIRC and by INV	Approximately 66 months	Time to first response is defined as time from the date of randomization to first response.
Time to initiation of new anticancer therapy	Approximately 66 months	Time to initiation of new anticancer therapy is defined as time from the date of randomization to the date of initiation of new anticancer therapy.
Health-Related Quality of Life (HRQoL) as Assessed by the European Organisation of Research and Treatment of Cancer-Quality of Life Questionnaire Non-Hodgkin Lymphoma High Grade Module 29 (EORTC-QLQ-NHL-HG29)	Approximately 66 months	Patient-reported symptom burden as measured by the EORTC-QLQ-NHL-HG29 questionnaire. The EORTC-QLQ-NHL-HG29 is the NHL-aggressive module of QLQ-C30; and it consists of 5 scales: Symptom burden due to disease and/or treatment (7 items), Neuropathy (2 items), Physical condition/Fatigue (5 items), Emotional impacts (4 items), and Worries/Fears health and functioning (11 items). Items are rated using a 4-point response scale ("not at all," "a little," "quite a bit," and "very much"). A higher score for all the multi-item scales and items represents a higher level of symptomatology or problems.
Health-Related Quality of Life (HRQoL) as Assessed by the European Organisation of Research and Treatment of Cancer-Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)	Approximately 66 months	Patient-reported physical condition/fatigue as measured by global health status (GHS) and physical function as measured by the EORTC-QLQ-C30 questionnaire. The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 =Not at all (best) to 4 =Very Much (worst) and 2 questions answered on a 7-point scale where 1 =Very poor (worst) to 7 =Excellent (best).
Number of participants with treatment-emergent adverse events (TEAEs)	From the first dose of study drug(s) to 30 days after the last dose; up to approximately 66 months	Number of participants with TEAEs, including laboratory values, vital signs, electrocardiogram results, and physical examination findings, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.

Trial Locations

Locations (294)

University of Alabama At Birmingham Hospital; 🇺🇸 Birmingham, Alabama, United States

Mayo Clinic Phoenix; 🇺🇸 Phoenix, Arizona, United States

Yale University, Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Memorial Cancer Institute, Memorial Healthcare System; 🇺🇸 Pembroke Pines, Florida, United States

Cleveland Clinic Florida; 🇺🇸 Weston, Florida, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Fort Wayne Medical Oncology and Hematology; 🇺🇸 Fort Wayne, Indiana, United States

Mission Cancer and Blood; 🇺🇸 Waukee, Iowa, United States

University of Maryland Greenebaum Comprehensive Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Dana Farber Cancer Institute Longwood Medical Center; 🇺🇸 Boston, Massachusetts, United States

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