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 (CELESTIAL-RRMCL)

BeOne Medicines

Status and phase: Enrolling; Phase 3

Conditions: B Cell Lymphoma; Mantle Cell Lymphoma

Treatments: Drug: Sonrotoclax; Drug: Placebo; Drug: Zanubrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06742996

CTR20250207 (Registry Identifier)

2024-515593-27-00 (EU Trial (CTIS) Number)

BGB-11417-302

Details and patient eligibility

About

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.

Full description

Mantle cell lymphoma (MCL) is a rare, aggressive type of B-cell lymphoma. B-cells are white blood cells that help fight infections. Lymphoma is a cancer in the lymphatic system. Sometimes this type of cancer can come back after treatment (relapse), or it does not respond to treatment or stops responding to treatment (refractory).

Sonrotoclax is a drug which blocks a protein called B-cell lymphoma-2 (Bcl-2). Zanubrutinib works by blocking a protein called Bruton tyrosine kinase (BTK). Bcl-2 and BTK help certain blood cancer cells live and grow. By blocking Bcl-2 and BTK, sonrotoclax and zanubrutinib may slow or stop cancer cell growth and help them die.

The purpose of this study is to test if sonrotoclax plus zanubrutinib is safe and if it works better in adults with R/R MCL compared to zanubrutinib plus placebo. The main goal is to compare how long participants live without their disease getting worse. The study will also evaluate side effects and overall safety.

This study has two treatment groups. Participants will be randomly assigned (by chance) to receive sonrotoclax plus zanubrutinib or zanubrutinib plus placebo. All study treatments will be taken by mouth. Placebo is a pill that looks like the study drug but has no active ingredient. Participants and the study doctor will not know what treatment group the participant is assigned to during the study, unless there is an urgent medical need.

The study will enroll approximately 300 adults with R/R MCL at multiple centers worldwide.

The overall time to participate in this study is up to approximately 7 years. Participants will make regular visits to the clinic for treatment, health checks, blood tests, and tumor imaging tests.

Note: Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.

Enrollment: 300 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically locally confirmed diagnosis of MCL based on the World Health Organization 2022 classification of Haematolymphoid Tumors (WHO-HAEM5), or based on International Consensus Classification (ICC)
• Ability to provide archival or fresh tumor tissue for retrospective central confirmation of MCL diagnosis
• 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 (BCL2i)
• Prior therapy with BTK degraders
• 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. Participants with refractory disease to BTKi therapy or relapse attributed to failure of BTKi therapy are ineligible.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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300 participants in 2 patient groups, including a placebo group

Arm A: sonrotoclax plus zanubrutinib

Experimental group

Description:

Sonrotoclax and zanubrutinib will be administered in combination.

Treatment:

Drug: Zanubrutinib

Drug: Sonrotoclax

Arm B: placebo plus zanubrutinib

Placebo Comparator group

Description:

Placebo and zanubrutinib will be administered in combination.

Treatment:

Drug: Placebo

Drug: Zanubrutinib