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

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.