A Study of Zanubrutinib, Obinutuzumab, and Sonrotoclax in People With Mantle Cell Lymphoma

NCT07799220 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 26-286
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 7

Brief Summary

The researchers are doing this study to find out whether the combination of zanubrutinib, obinutuzumab, and sonrotoclax (BOSon) is an effective treatment approach for people with mantle cell lymphoma (MCL).

Conditions

Mantle Cell Lymphoma

Keywords

Zanubrutinib; Obinutuzumab; Sonrotoclax (BOSon); stage II-IV; 26-286

Outcome Measures

Primary Outcomes (1)

• evaluate BOSon

  through determination of the PET CR-uMRD6 rate

  up to 3 years

Secondary Outcomes (1)

• Proportion of Participants with Tumor Lysis Syndrome (TLS)

  up to 3 years

Study Arms (1)

Zanubrutinib, Obinutuzumab, and Sonrotoclax

EXPERIMENTAL

Zanubrutinib will be administered PO twice daily of each 28-day cycle. Obinutuzumab will be administered on days 1, 8, and 15 of cycle 1 and IVPB on day 1 of cycles 2-8. Sonrotoclax will be initiated on C2D1 using the ramp-up schedule.

Drug: Zanubrutinib; Drug: Obinutuzumab; Drug: Sonrotoclax

Interventions

Zanubrutinib DRUG

PO twice daily of each 28-day cycle

Zanubrutinib, Obinutuzumab, and Sonrotoclax

Obinutuzumab DRUG

IVPB on days 1, 8, and 15 of cycle 1; and IVPB on day 1 of cycles 2-8

Zanubrutinib, Obinutuzumab, and Sonrotoclax

Sonrotoclax DRUG

Sonrotoclax will be initiated on C2D1 using the ramp-up schedule

Zanubrutinib, Obinutuzumab, and Sonrotoclax

Eligibility Criteria

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

You may qualify if:

• Documentation of disease: Patients must have pathologically confirmed MCL at the treating institution
• Evaluable disease, stage II-IV
• o Patients with non-nodal leukemic MCL may enroll even without FDG PET/CT measurable disease; an end-of-treatment BMBx to confirm response is required in such cases
• Age ≥ 65 years at screening
• If Age \<65, then required to fulfill one of the following criteria disqualifying for autologous transplant (autoHCT):
• Comorbid disease(s) such as CAD, heart failure, pulmonary dysfunction, liver, or kidney dysfunction that precludes autoHCT based on expected increased morbidity
• ECOG ≥ 2 (Appendix 1) due to comorbidities
• Ejection fraction ≥ 35% and \<45%
• Impaired pulmonary function test with DLCO \<50% of expected
• Medical conditions that in the opinion of the treating physician in consultation with the MSK PI or Co-PI preclude autoHCT
• Not pregnant and not nursing
• Required organ function:
• o Adequate hematologic function, defined as:
• Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 or \>= 500 cells/mm3 if cytopenia is related to MCL (bone marrow involvement)
• Platelets ≥ 75,000 cells/mm3 or 25,000 if related to MCL

You may not qualify if:

• Active infection requiring parenteral antibiotic(s)
• History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
• Patients unable to swallow capsules or those with disease(s) or conditions significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic/active inflammatory bowel disease, or partial or complete bowel obstruction
• Patients undergoing major surgery within 4 weeks of the first dose of study drug
• Patients with ongoing alcohol or drug addiction or any psychiatric condition(s) which would compromise ability to comply with study procedures
• Patients receiving treatment with any moderate or strong CYP3A4 inhibitor or moderate or strong CYP3A4 inducer ≤ 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug or requiring ongoing treatment with a moderate or strong CYP3A inhibitor or a moderate or strong CYP3A inducer are ineligible
• Concurrent participation in another therapeutic clinical trial
• Patients with a prior or concurrent malignancy except for those whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Concomitant Medications: Concomitant medications use should only exclude patients from trial participation when clinically relevant known or predicted drug-drug interactions (see Section 5, Appendix 8) or potential overlapping toxicities will impact safety or efficacy.
• History of allergic reaction to the study agent(s), compounds of similar chemical or biologic composition to the study agent (s) (or any of its excipients).
• Prior treatment:
• Previous systemic therapy is prohibited
• Systemic steroids are allowed for urgent disease control, improvement of performance status, or non-cancer indications
• Must be \<14 days' duration and ≤ 100 mg/day prednisone equivalent
• Steroids must be discontinued prior to C1D1 study treatment

Sponsors & Collaborators

• BeOne Medicines: collaborator
• Memorial Sloan Kettering Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (7)

Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activites)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

East White Plains, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

zanubrutinib; obinutuzumab

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

Study Officials

• Zachary Epstein-Peterson, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zachary Epstein-Peterson, MD

CONTACT

646-608-4176; epsteinz@mskcc.org

Anita Kumar, MD

CONTACT

646-608-3780

Study Design

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

Model Details: This is a multicenter phase II study of zanubrutinib, obinutuzumab, and sonrotoclax (BOSon) as frontline therapy for transplant-ineligible patients with mantle cell lymphoma (MCL).

Study Record Dates

• First Submitted: August 26, 2026
• First Posted: September 2, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: September 10, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Access Criteria: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Locations

US (7)