Mosunetuzumab and Polatuzumab Vedotin for the Treatment of Patients With Relapsed or Refractory Grade 1-3a Follicular Lymphoma

NCT06453044 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 23003NCI-2024-04429P30CA033572
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial tests how well mosunetuzumab and polatuzumab vedotin works in treating patients with grade 1-3a follicular lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Mosunetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Polatuzumab vedotin is a monoclonal antibody, polatuzumab, linked to a toxic agent called vedotin. Polatuzumab attaches to CD79B positive cancer cells in a targeted way and delivers vedotin to kill them. Giving mosunetuzumab and polatuzumab vedotin may kill more cancer cells in patients with relapsed or refractory grade 1-3a follicular lymphoma.

Conditions

Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3a Follicular Lymphoma; Refractory Grade 1 Follicular Lymphoma; Refractory Grade 2 Follicular Lymphoma; Refractory Grade 3a Follicular Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence of grade 3 or higher adverse events (AEs)

  Unacceptable toxicity will be defined as events occurring during the first 2 cycles of treatment that is at least possibly related to study treatment. Observed toxicities will be summarized by type, severity, and attribution.

  Up to completion of first 2 cycles of treatment - each cycle is 28 days

• Complete response (CR) rate

  CR rate will be defined as the proportion of response-evaluable participants that achieve a best response of CR after the start of protocol therapy and prior to disease progression and/or start of other anti-lymphoma therapy. CR rate will be estimated along with the 95% exact binomial confidence interval.

  Up to 36 months after last dose of protocol therapy

Secondary Outcomes (10)

• Incidence of AEs

  Up to 30 days from last dose of protocol therapy

• Overall response rate (ORR)

  Up to 36 months after last dose of protocol therapy

• Time to first CR

  At start of protocol therapy to CR up to 36 months after last dose of protocol therapy

• Time to best response

  At start of protocol therapy to first best response up to 36 months after last dose of protocol therapy

• Duration of response (DOR)

  At first PR or CR to progression or death up to 36 months after last dose of protocol therapy

Study Arms (1)

Treatment (mosunetuzumab, polatuzumab vedotin)

EXPERIMENTAL

Patients receive polatuzumab vedotin IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mosunetuzumab SC on days 1, 8 and 15 of cycle 1 and day 1 of remaining cycles. Cycles repeat every 21 days for up to 8-17 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and CT, PET/CT, or MRI throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Biological: Mosunetuzumab; Drug: Polatuzumab Vedotin; Procedure: Positron Emission Tomography; Other: Questionnaire Administration

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (mosunetuzumab, polatuzumab vedotin)

Computed Tomography PROCEDURE

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (mosunetuzumab, polatuzumab vedotin)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (mosunetuzumab, polatuzumab vedotin)

Mosunetuzumab BIOLOGICAL

Given SC

Also known as: Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody BTCT4465A, BTCT 4465A, BTCT-4465A, BTCT4465A, CD20/CD3 BiMAb BTCT4465A, Lunsumio, Mosunetuzumab-axgb, RG 7828, RG-7828, RG7828, RO7030816

Treatment (mosunetuzumab, polatuzumab vedotin)

Polatuzumab Vedotin DRUG

Given IV

Also known as: ADC DCDS4501A, Antibody-Drug Conjugate DCDS4501A, DCDS4501A, FCU 2711, polatuzumab vedotin-piiq, Polivy, RG7596, Ro 5541077-000

Treatment (mosunetuzumab, polatuzumab vedotin)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (mosunetuzumab, polatuzumab vedotin)

Questionnaire Administration OTHER

Ancillary Studies

Treatment (mosunetuzumab, polatuzumab vedotin)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Be willing to provide tissue from a fresh core or excisional biopsy (performed as standard of care) of a tumor lesion prior to starting study therapy or from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Histologically confirmed diagnosis of follicular lymphoma grade 1-3a according to the World Health Organization (WHO) classification. Note: A history of diffuse large B-cell lymphoma (DLBCL) and/or grade 3b follicular lymphoma is allowed (follicular large B-cell lymphoma in the WHO 5th classification of mature B-cell lymphoma) but these cannot be present at the time of study enrollment. Enrollment of any such cases on this study must receive prior approval by the study PI
• Relapsed/ refractory disease after at least one prior line of therapy. Relapse must have been confirmed histologically
• Active disease requiring treatment per treating physician's decision
• Radiographically measurable disease by Lugano criteria (e.g., one or more nodal sites of disease ≥ 1.5 cm and/or at least one extranodal site of disease ≥ 1.0 cm in longest dimension)
• Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
• WITHOUT BONE MARROW INVOLVEMENT BY LYMPHOMA: Absolute neutrophil count (ANC) ≥ 1,000/mm\^3. NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
• WITH BONE MARROW INVOLVEMENT BY LYMPHOMA AND/OR DISEASE-RELATED NEUTROPENIAS: ANC ≥ 500/mm\^3. NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
• WITHOUT BONE MARROW INVOLVEMENT BY LYMPHOMA: Platelets ≥ 75,000/mm\^3. NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement
• WITH BONE MARROW INVOLVEMENT BY LYMPHOMA AND/OR DISEASE-RELATED CYTOPENIAS: Platelets ≥ 50,000/mm\^3. NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement

You may not qualify if:

• Prior treatment with mosunetuzumab or other CD20-directed bispecific antibodies. Prior exposure to 2 or less doses without evidence of resistance is allowed
• Prior treatment with polatuzumab vedotin or with an antibody-drug conjugate containing monomethyl auristatin E (MMAE). Prior exposure to 2 or less doses without evidence of resistance is allowed
• Allogeneic stem cell transplant within 2 years prior to day 1 of protocol therapy, requires immunosuppression, or has evidence of active-versus-host-disease
• Patients who had an allogeneic transplant \> 2 years prior to day 1 of protocol therapy must additionally have been stable off immunosuppressive agents for ≥ 2 months
• Autologous stem cell transplant within 100 days prior to day 1 of protocol therapy
• Chimeric antigen receptor (CAR)-T therapy within 30 days prior to day 1 of protocol therapy
• Prior use of any anti-lymphoma treatment with monoclonal antibody, radioimmunoconjugate or antineoplastic drug conjugate (ADC) within 4 weeks prior to day 1 of protocol therapy
• Treatment with any chemotherapeutic agent, or treatment with any other anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to day 1 of protocol therapy
• Treatment with radiotherapy within 2 weeks prior to day 1 of protocol therapy
• If patients have received radiotherapy within 4 weeks prior to prior to day 1 of protocol therapy, patients must have at least one measurable lesion outside of the radiation field. Patients who have only one measurable lesion that was previously irradiated but subsequently progressed are eligible
• Live vaccine within 30 days prior to day 1 of protocol therapy
• Systemic immunosuppressive therapy (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[TNF\] agents) with the exception of corticosteroid treatment for lymphoma symptom control must be tapered down to ≤ 10 mg/day prednisone or equivalent 14 days prior to day 1 of protocol therapy. Exceptions are:
• Inhaled or topical steroids
• Use of mineralocorticoids for management of orthostatic hypotension
• Use of physiologic doses of corticosteroids for management of adrenal insufficiency

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

City of Hope Orange County Lennar Foundation Cancer Center

Irvine, California, 92618, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

Specimen Handling; Magnetic Resonance Spectroscopy; polatuzumab vedotin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Matthew Mei, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthew Mei, MD

CONTACT

626-359-8111; mamei@coh.org

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 30, 2024
• First Posted: June 11, 2024
• Study Start: September 9, 2024
• Primary Completion (Estimated): March 14, 2028
• Study Completion (Estimated): March 14, 2028
• Last Updated: September 24, 2025

Record last verified: 2025-09

Locations

US (2)