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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

BeOne Medicines AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 May 2025 → ongoing

Decision date (initial)

2025-04-28

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

BeiGene, Ltd

External identifiers

EU CT number

2024-515593-27-00

WHO UTN

U1111-1309-4704

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To demonstrate superiority of sonrotoclax plus zanubrutinib over placebo plus zanubrutinib as measured by progression-free survival (PFS) determined by a blinded independent review committee (BIRC).

Secondary objectives 4

1. To compare the efficacy of sonrotoclax plus zanubrutinib with that of placebo plus zanubrutinib as measured by overall survival (OS).
2. To evaluate efficacy, as measured by the following: 1) Progression-free survival (PFS) determined by investigator. 2) Overall response rate (ORR), as determined by blinded independent review committee (BIRC) and by investigator assessment, per Lugano 2014 criteria. 3) Complete response rate (CRR), as determined by BIRC and by investigator. 4) Duration of response (DOR), as determined by BIRC and by investigator. 5) Time to first response, as determined by BIRC and by investigator.
3. To evaluate patient-reported disease and treatment symptoms.
4. To evaluate safety and tolerability.

Conditions and MedDRA coding

relapsed or refractory mantle cell lymphoma (R/R MCL)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved. BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, and shared when it is feasible to do so without compromising the privacy of study participants. Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data along with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Histologically confirmed diagnosis of MCL based on the World Health Organization 2022 classification of Haematolymphoid Tumors (WHOHAEM5), or based on International Consensus Classification (ICC)
2. 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
3. Relapsed or refractory disease after the last line of therapy
4. 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
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
6. Adequate organ function

Exclusion criteria 7

1. Prior therapy with B-cell lymphoma-2 inhibitor
2. 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
3. Prior autologous stem cell transplantation or chimeric antigen receptor T-cell therapy within 3 months before first dose of study drug
4. Prior allogeneic stem cell transplant within 6 months of the first dose of the study drug
5. Known central nervous system involvement by lymphoma
6. Clinically significant cardiovascular disease
7. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS), as assessed by blinded independent review committee (BIRC), defined as the time from randomization to the date of progression or death, whichever occurs first.

Secondary endpoints 9

1. Overall survival (OS), defined as the time from randomization to the date of death from any cause.
2. Progression-free survival (PFS) as determined by investigator.
3. Overall response rate (ORR) as determined by BIRC and by investigator per the Lugano 2014 criteria. ORR is defined as the proportion of patients who achieved a best overall response of partial response or complete response (CR).
4. Duration of response (DOR) as determined by BIRC and by investigator. It is defined as the time from the first qualifying response to the date of progression or death, whichever occurs first.
5. Complete response rate (CRR), as determined by BIRC and by investigator. It is defined as the proportion of patients who achieved a best overall response of CR.
6. Time to first response as determined by BIRC and by investigator. It is defined as time from randomization to first response.
7. Time to initiation of new anticancer therapy.
8. Patient-reported symptom burden and physical condition/fatigue as measured 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) questionnaire, and global health status (GHS) and physical function as measured by the European Organisation of Research and Treatment of Cancer-Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30).
9. Incidence and severity of treatment-emergent adverse events (TEAE)s graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Comparator 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

BeOne Medicines AG

Sponsor organisation

BeOne Medicines AG

Address

Aeschengraben 27

City

Basel

Postcode

4051

Country

Switzerland

Scientific contact point

Organisation

Beigene Ltd.

Contact name

BeOne Medical Officer

Public contact point

Organisation

Beigene Ltd.

Contact name

BeOne Medical Officer

Third parties 15

Locations

6 EU/EEA countries · 28 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 109 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications