This phase II trial compares the effect of mosunetuzumab alone to mosunetuzumab with zanubrutinib or polatuzumab vedotin in patients with marginal zone lymphoma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Mosunetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Zanubrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers such as marginal zone lymphoma at abnormal levels. This may help keep cancer cells from growing and spreading. Polatuzumab vedotin is a monoclonal antibody, called polatuzumab, linked to a drug, called monomethyl auristatin E. Polatuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD79B receptors, and delivers monomethyl auristatin E to kill them. Giving mosunetuzumab alone or with zanubrutinib or polatuzumab vedotin may work well for treating relapsed or refractory marginal zone lymphoma.
PRIMARY OBJECTIVES: I. To compare complete response (CR) rates in participants with relapsed/refractory marginal zone lymphoma randomized to mosunetuzumab subcutaneously (SQ) with or without zanubrutinib (Arm 2 versus Arm 1). II. To compare CR rates in participants with relapsed/refractory marginal zone lymphoma randomized to mosunetuzumab SQ with or without polatuzumab vedotin (Arm 3 versus Arm 1). SECONDARY OBJECTIVES: I. To compare progression-free survival (PFS) between: Ia. Participants randomized to mosunetuzumab SQ with or without zanubrutinib (Arm 2 versus Arm 1); Ib. Participants randomized to mosunetuzumab SQ with or without polatuzumab vedotin (Arm 3 versus Arm 1). II. To compare overall survival (OS) between: IIa. Participants randomized to mosunetuzumab SQ with or without zanubrutinib (Arm 2 versus Arm 1); IIb. Participants randomized to mosunetuzumab SQ with or without polatuzumab vedotin (Arm 3 versus Arm 1). III. To compare overall response rate (ORR defined as complete responses \[CR\] and partial responses \[PR\]) between: IIIa. Participants randomized to mosunetuzumab SQ with or without zanubrutinib (Arm 2 versus Arm 1); IIIb. Participants randomized to mosunetuzumab SQ with or without polatuzumab vedotin (Arm 3 versus Arm 1). IV. To estimate duration of response (DoR) among responders within each treatment arm. V. To evaluate the frequency and severity of adverse events (AE) observed in each treatment arm. PATIENT REPORTED OUTCOMES-COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (PRO-CTCAE) OBJECTIVE: I. Compare the incidence and severity of symptomatic adverse events (AEs) between each treatment arm utilizing PRO-CTCAE, including diarrhea, neuropathy, bruising, palpitations, and concentration/memory. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 3 arms. ARM 1: Patients receive mosunetuzumab subcutaneously (SC) on days 1, 8 and 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients who achieve complete response (CR) or progressive disease (PD) discontinue treatment. Patients with partial response (PR) or stable disease (SD) continue treatment for an additional 9 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo positron emission tomography (PET)/computed tomography (CT), CT, clinically indicated bone marrow biopsy, and blood sample collection throughout the study. ARM 2: Patients receive mosunetuzumab SC on days 1, 8 and 15 of cycle 1 and day 1 of subsequent cycles. Patients also receive zanubrutinib orally (PO) once daily (QD) or twice daily (BID) on days 1-21 of each cycle. Cycles repeat every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients who achieve CR or PD discontinue treatment. Patients with PR or SD continue treatment for an additional 9 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT, CT, clinically indicated bone marrow biopsy, and blood sample collection throughout the study. ARM 3: Patients receive mosunetuzumab SC on days 1, 8 and 15 of cycle 1 and day 1 of subsequent cycles. Patients also receive polatuzumab vedotin IV, over 30-90 minutes, on day 1 of each cycle (cycles 1-6 only). Cycles repeat every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients who achieve CR or PD discontinue treatment. Patients with PR or SD continue treatment with mosunetuzumab alone for an additional 9 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT, CT, clinically indicated bone marrow biopsy, and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 6 months for 3 years then annually until year 5.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
138
Undergo blood sample collection
Undergo bone marrow biopsy
Undergo CT scan
Given SC
Given IV
Undergo PET scan
Ancillary studies
Given PO
Complete response rate (arm 1 versus arm 2)
Defined by the Lugano Classification.
Time frame: Up to 5 years
Complete response rate (arm 1 versus arm 3)
Defined by the Lugano Classification.
Time frame: Up to 5 years
Progression free survival
Will be calculated using the method of Kaplan-Meier and compared using a log-rank test.
Time frame: From date of randomization to date of first observation of progressive disease, transformation to diffuse large B cell lymphoma, or death due to any cause, up to 5 years
Overall survival
Will be calculated using the method of Kaplan-Meier and compared using a log-rank test.
Time frame: From date of randomization to date of death due to any cause, up to 5 years
Overall response rate
Defined as complete responses and partial responses.
Time frame: Up to 5 years
Duration of response
Will be calculated using the method of Kaplan-Meier and compared using a log-rank test.
Time frame: From date of first documentation of response to treatment to date of first documentation of progression, transformation to diffuse large B cell lymphoma, or death due to any cause among participants who achieve a response, up to 5 years
Incidence of adverse events
Time frame: Up to 5 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.