Sonrotoclax Plus Zanubrutinib in Patients With Relapsed/Refractory Mantle Cell Lymphoma Planned for Standard of Care CAR-T Cell Therapy

NCT07341191 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: I245
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the effects of adding two oral medications (sonrotoclax plus zanubrutinib) to standard of care chimeric antigen receptor (CAR-T) cell therapy in participants with mantle cell lymphoma.

Conditions

Mantle Cell Lymphoma

Keywords

CAR-T; Relapsed; Refractory; BTK inhibitor; BCL2 inhibitor

Outcome Measures

Primary Outcomes (1)

• Complete response post CAR-T

  3.5 years

Secondary Outcomes (4)

• Objective Response Rate assessed by the Lugano Classification

  3.5 years

• 1 year Progression-Free Survival

  4 years

• Overall Survival

  4 years

• Number and Severity of Adverse Events

  3.5 years

Study Arms (1)

Zanubrutinib + Sonrotoclax

EXPERIMENTAL

Drug: Zanubrutinib; Drug: Sonrotoclax; Biological: CAR-T Cell Therapy

Interventions

Zanubrutinib DRUG

assigned at enrollment

Zanubrutinib + Sonrotoclax

Sonrotoclax DRUG

assigned at enrollment

Zanubrutinib + Sonrotoclax

CAR-T Cell Therapy BIOLOGICAL

Standard of Care

Zanubrutinib + Sonrotoclax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have histologically confirmed mantle cell lymphoma that is relapsed or refractory after at least one prior line of systemic therapy
• Eligible for and planned to receive Health Canada approved CAR-T.
• Have a formalin fixed paraffin embedded tumour tissue block available and must have provided informed consent for the release of the block.
• Presence of radiologically documented disease.
• Measurable disease (one site bidimensionally measurable).
• Age ≥ 18 years.
• Have an ECOG performance status of 0, 1 or 2
• Anticipated life expectancy of ≥ 6 months
• Adequate hematologic and biochemical parameters
• Must have received prior systemic therapy as shown below;
• At least one line of systemic therapy including a Bruton's Tyrosine Kinase inhibitor (BTKi).
• Participants who have previously received venetoclax, sonrotoclax, or any other BCL2 inhibitor (BCL2i) are eligible as long as progressive disease did not occur within 6 months of the last dose of BCL2i. Participants with progressive disease during BCL2i therapy or within 6 months of last dose are not eligible.
• Participants must enter the study while on a BTKi or enroll to a substudy of the protocol to receive zanubrutinib for a minimum duration prior to enrolling to the main study.
• Participants previously exposed to zanubrutinib are eligible irrespective of response to treatment.
• Participants entering the study while on a BTKi must have their BTKi switched to zanubrutinib supplied through the study.

You may not qualify if:

• Participants on active anticancer therapy for other advanced or metastatic malignancies.
• Concurrent treatment with other anti-cancer therapy
• Serious illnesses or medical conditions which would not permit the participant to be managed according to the protocol.
• Known hypersensitivity to the study drug(s) or their components.
• Prior CD19-directed CAR-T at any time, autologous hematopoietic cell transplantation within 6 weeks, or allogeneic hematopoietic cell transplantation within 3 months. Allogeneic hematopoietic cell transplantation recipients must be free of clinically-significant graft-versus-host disease (GvHD) and must be off immunosuppression for GvHD for at least 4 weeks before enrollment.
• Untreated and/or uncontrolled cardiovascular conditions and/or symptomatic cardiac dysfunction (including cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects) or unstable angina congestive heart failure or myocardial infarction within the previous year.
• Active, uncontrolled bacterial, fungal, or viral infection within 14 days prior to enrollment
• Pregnant or breastfeeding women.
• Inability to discontinue use of moderate or strong CYP3A inducers or inhibitors during the ramp-up treatment period with sonrotoclax.
• Live vaccination within 4 weeks prior to enrollment or who plan to receive a live vaccine during treatment or within 90 days post last dose.
• Inability to swallow capsules or tablets or have any diseases significantly affecting GI function
• Active central nervous system (CNS) disease; Participants with stable CNS disease are eligible.
• Growth factors within 28 days prior to enrollment.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• BeOne Medicines: collaborator

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Recurrence

Interventions

zanubrutinib; Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Diego Villa

  BCCA-Vancouver Cancer Centre

  STUDY CHAIR

• Robert Puckrin

  Tom Baker Cancer Centre, Calgary, AB Canada

  STUDY CHAIR

Central Study Contacts

Annette Hay

CONTACT

613-533-6430; ahay@ctg.queensu.ca

Laura Pearce

CONTACT

613-533-6430; lpearce@ctg.queensu.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2026
• First Posted: January 14, 2026
• Study Start: March 31, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030
• Last Updated: March 25, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share