Mosunetuzumab and Polatuzumab Vedotin for Untreated Follicular Lymphoma

NCT05410418 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 202207147
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II clinical trial studies the combination of mosunetuzumab and polatuzumab vedotin in order to see how well it works in patients with untreated follicular lymphoma. Mosunetuzumab is an antibody that has been engineered to attach to two target cells in the immune system: T cells that normally perform tasks like killing virus-infected cells, and cancerous B cells. Mosunetuzumab has been designed to direct these T cells to kill the cancerous B cells instead. Polatuzumab vedotin is an antibody-drug conjugate that attaches to certain cancerous B cells and then delivers a drug specifically to those cells.

Conditions

Lymphoma, Follicular; Follicular Lymphoma

Keywords

lymphoma; follicular lymphoma; antibody-drug conjugate; B-NHL; B cell non-Hodgkin lymphoma; mosunetuzumab; polatuzumab vedotin; bispecific antibody

Outcome Measures

Primary Outcomes (1)

• Number of participants with complete response (CR) as best response

  CR determined by response to treatment by PET-CT at end of treatment per Deauville 5-point scale (Lugano 2014 criteria). The Deauville scale is scored from 1 to 5, with 1 indicating no uptake on PET-CT and 5 indicating markedly increased uptake on PET-CT.

  Through completion of treatment (estimated to be 1 year)

Secondary Outcomes (27)

• Number of participants with complete response (CR)

  After Cycle 8 (each cycle is 21 days; estimated to be 6 months)

• Number of participants with partial response (PR)

  After Cycle 8 (each cycle is 21 days; estimated to be 6 months)

• Number of participants with partial response (PR)

  Through completion of treatment (estimated to be 1 year)

• Overall response rate (ORR) as measured by number of participants with complete response (CR) and partial response (PR)

  After Cycle 8 (each cycle is 21 days; estimated to be 6 months)

• Overall response rate (ORR) as measured by number of participants with complete response (CR) and partial response (PR)

  Through completion of treatment (estimated to be 1 year)

Study Arms (1)

Mosunetuzumab and Polatuzumab Vedotin

EXPERIMENTAL

Patients receive CD3xCD20 bispecific antibody mosunetuzumab administered subcutaneously in combination with CD79b directed ADC polatuzumab vedotin administered intravenously. Mosunetuzumab and polatuzumab vedotin are given in combination for 6 cycles. Mosunetuzumab is given on Days 1, 8, and 15 of cycle 1 and then Day 1 thereafter, and polatuzumab vedotin is given on Day 1. After 6 cycles, patients continue on mosunetuzumab alone for 2 additional cycles. Patients undergo scans at the end of cycle 8, and if those scans show a complete response, patients will stop any further treatment and will enter follow-up. Patients with a partial response or stable disease on scans at the end of cycle 8 may receive up to 9 additional cycles of mosunetuzumab in the absence of disease progression or unacceptable toxicity. All cycles are planned to be 21 days.

Drug: Mosunetuzumab; Drug: Polatuzumab vedotin

Interventions

Mosunetuzumab DRUG

Mosunetuzumab is administered subcutaneously using a "step-up" dosing strategy. The initial dose on C1D1 will be 5 mg, and doses thereafter will be 45 mg.

Also known as: RO7030816, BTCT4465A

Mosunetuzumab and Polatuzumab Vedotin

Polatuzumab vedotin DRUG

Polatuzumab vedotin is administered intravenously over 90 minutes for the initial dose, and over 30 minutes thereafter.

Also known as: RO5541077, DCDS4501A

Mosunetuzumab and Polatuzumab Vedotin

Eligibility Criteria

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

You may qualify if:

• Diagnosis of follicular lymphoma grade 1-3A, stage II-IV by Ann Arbor criteria.
• One or more of the following criteria (adapted from GELF criteria):
• Any nodal or extranodal tumor mass with diameter \> 7 cm
• Involvement of at least 3 nodal sites, each with diameter \> 3 cm
• Presence of any systemic or B symptoms
• Splenic enlargement with inferior margin below the umbilical line
• Compression syndrome (e.g., ureteral, orbital, gastrointestinal)
• Pleural or peritoneal serous effusion (irrespective of cell content)
• Cytopenia(s) attributable to lymphoma
• At least 18 years of age.
• ECOG performance status ≤ 2
• Adequate hematologic and organ function (unless due to underlying lymphoma per the investigator; see below), defined as follows:
• Absolute neutrophil count ≥ 1,000/mcL
• Platelets ≥ 75,000/mcL
• Hemoglobin ≥ 8 g/dL

You may not qualify if:

• Prior history of aggressive B cell lymphoma such as diffuse large B cell lymphoma or high-grade B cell lymphoma.
• Known history of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents.
• Known history of macrophage activation syndrome (MAS) or hemophagocytic lymphohistiocytosis (HLH).
• Current or past history of CNS lymphoma.
• Any prior systemic therapy for follicular lymphoma.
• Treatment with radiotherapy within 2 weeks prior to the first dose of mosunetuzumab (otherwise one measurable lesion outside of the radiation field must remain).
• Treatment with any anti-CD20 monoclonal antibody within 4 weeks of Day 1 of Cycle 1.
• Current or recent history (within the last 6 months) of CNS disease, such as stroke, epilepsy CNS vasculitis, or serious progressive neurodegenerative disease, with clinically significant symptoms.
• Treatment with systemic immunosuppressive medications, including but not limited to prednisone (\> 20 mg), azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1.
• \* Note: The use of inhaled corticosteroids, mineralocorticoids for management of orthostatic hypotension, and single dose dexamethasone for nausea or B symptoms is permitted.
• History of solid organ transplantation.
• History of allogeneic stem cell transplantation.
• Prior treatment with chimeric antigen receptor T cell therapy within 30 days before Day 1 of Cycle 1.
• History of severe allergic or anaphylactic reaction to humanized, chimeric, or murine monoclonal antibodies (mAbs).
• Known hypersensitivity to biopharmaceuticals produced in CHO cells or any component of the mosunetuzumab formulation, including mannitol.

Sponsors & Collaborators

• Genentech, Inc.: collaborator
• Institute for Follicular Lymphoma: collaborator
• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma; Lymphoma, B-Cell

Interventions

polatuzumab vedotin

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• David A Russler-Germain, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 26, 2022
• First Posted: June 8, 2022
• Study Start: October 24, 2022
• Primary Completion: September 18, 2025
• Study Completion (Estimated): April 24, 2029
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)