Mosunetuzumab +/− Polatuzumab Vedotin and Obinutuzumab for Lymphoma

Overseen By Ryan Lynch, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: CYP3A4 modulators

Disqualifiers: Autoimmune disease, Organ transplant, Neuropathy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 14

42 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial tests the effects of mosunetuzumab with or without polatuzumab vedotin and obinutuzumab for the treatment of patients with indolent B-cell non-Hodgkin lymphoma. Mosunetuzumab and obinutuzumab are monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Polatuzumab vedotin is a monoclonal antibody, called polatuzumab, linked to a chemotherapy drug, called vedotin. 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 vedotin to kill them. Giving mosunetuzumab with polatuzumab vedotin and obinutuzumab may work better in treating patients with untreated indolent B-cell non-Hodgkin lymphoma.

Research Team

Ryan Lynch, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

Adults with untreated indolent B-cell non-Hodgkin lymphoma who have symptoms like pain, organ enlargement, or low blood counts due to the disease. They must be able to perform daily activities (0-2 on ECOG scale), have adequate organ function, and agree to use effective contraception. Excluded are pregnant women, those with certain infections or autoimmune diseases, recent monoclonal antibody treatment, uncontrolled illnesses, or a history of other cancers.

Inclusion Criteria

AST (SGOT) and ALT (SGPT) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver involvement

I have a large tumor or multiple tumors.

My condition is follicular lymphoma, grade 1-2 or 3a.

Exclusion Criteria

Positive test results for chronic hepatitis B infection

You have had another type of cancer that could affect the study or make it difficult to understand the results, unless the principal investigator approves it.

I have had a solid organ transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Patients receive mosunetuzumab subcutaneously on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles. Treatment repeats every 21 days for 8 cycles.

24 weeks

8 cycles with multiple visits per cycle

Treatment Part B

Patients who do not achieve a complete response receive obinutuzumab and polatuzumab vedotin intravenously. Treatment repeats every 21 days for 6 cycles.

18 weeks

6 cycles with multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 5 years

Treatment Details

Interventions

• Mosunetuzumab
• Obinutuzumab
• Polatuzumab Vedotin

Trial Overview The trial is testing mosunetuzumab alone or combined with polatuzumab vedotin and obinutuzumab in patients. These drugs are types of targeted therapy that may block cancer growth by binding to specific proteins on cancer cells; one also delivers chemotherapy directly to the cell.

Participant Groups

Group I: Treatment (mosunetuzumab, obinutuzumab, polatuzumab vedotin) Experimental Treatment 9 Interventions

PART A: Patients receive mosunetuzumab SC over 30 seconds - 2 minutes on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-PET/CT, PET/CT and CT scans, bone marrow biopsy, bone marrow aspirate, and collection of blood samples throughout the study. PART B: Beginning cycle 9, patients who do not achieve a CR receive obinutuzumab IV on day 1, 8, and 15 of cycle 9 and day 1 of subsequent cycles and polatuzumab vedotin IV on day 1. Treatment repeats every 21 day for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, PET/CT, and FDG-PET scans, bone marrow biopsy, bone marrow aspirate, and collection of blood samples throughout the study.

Mosunetuzumab is already approved in European Union, United States for the following indications:

Approved in European Union as Lunsumio for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Approved in United States as Lunsumio for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD