NCT06735664

Zanubrutinib in Combination With Odronextamab for the Treatment of Patients With Richter's Transformation

A Phase I Study of Covalent BTK Inhibitor Zanubrutinib in Combination With a CD3-CD20 Bispecific Antibody Odronextamab in Patients With Richter's Transformation

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 23 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety and side effects of zanubrutinib in combination with odronextamab and how well it works in treating patients with Richter's transformation. Zanubrutinib, a tyrosine kinase inhibitor, blocks a protein called Bruton tyrosine kinase (BTK), which may help keep cancer cells from growing. Odronextamab is a bispecific monoclonal antibody that can bind to two different antigens at the same time. Odronextamab binds to CD20 found on B-cells (a type of white blood cell) and on many B-cell cancers and to CD3 on T-cells (also a type of white blood cell) and may interfere with the ability of cancer cells to grow and spread. Giving zanubrutinib in combination with odronextamab may be safe, tolerable and/or effective in treating patients with Richter's transformation.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate safety and tolerability of zanubrutinib administered in combination with odronextamab in patients with Richter's transformation (RT). SECONDARY OBJECTIVE: I. To evaluate efficacy of zanubrutinib administered in combination with odronextamab, based on overall response rate (ORR), complete response (CR) rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). EXPLORATORY OBJECTIVE: I. To characterize the T-cell population balance in patients treated with zanubrutinib and odronextamab. OUTLINE: Patients receive odronextamab intravenously (IV) over 4 hours on days 1, 2, 8, 9, 15 and 16 of cycle 1 and over 1-4 hours on days 1, 8 and 15 of cycles 2-4 and then on days 1 and 15 of remaining cycles. Patients with CR at cycle 9 may receive odronextamab on day 1 of remaining cycles. Starting with cycle 2, patients also receive zanubrutinib orally (PO) once daily (QD) or twice daily (BID) of each cycle. Cycles repeat every 21 days for cycles 1-4 in the absence of disease progression or unacceptable toxicity then repeat every 28 days for up to cycle 12. After 12 cycles, patients may continue zanubrutinib at investigator's discretion. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) and optional bone marrow biopsy at screening and ultrasound guided biopsy of lymph node at screening and during days 2-12 of cycle 2. Additionally, patients undergo blood sample collection and positron emission tomography (PET), or computed tomography (CT) throughout the study. After completion of study treatment, patients are followed up at 4 and 12 weeks then every 6 months for up to 3 years.

Conditions

• Recurrent Transformed Chronic Lymphocytic Leukemia
• Refractory Transformed Chronic Lymphocytic Leukemia
• Richter Syndrome
• Transformed Chronic Lymphocytic Leukemia to Diffuse Large B-Cell Lymphoma

Interventions

Type	Name	Description
PROCEDURE	Biopsy	Undergo ultrasound guided biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Biopsy	Undergo optional bone marrow biopsy
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Echocardiography	Undergo ECHO
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA
BIOLOGICAL	Odronextamab	Given IV
PROCEDURE	Positron Emission Tomography	Undergo PET
PROCEDURE	Ultrasound Imaging	Undergo ultrasound guided biopsy
DRUG	Zanubrutinib	Given PO

Timeline

• Start date: 2025-08-14
• Primary completion: 2027-12-13
• Completion: 2027-12-13
• First posted: 2024-12-16
• Last updated: 2025-09-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study