Mosunetuzumab (IV): Participants will receive intravenous (IV) mosunetuzumab.
Mosunetuzumab (SC): Participants will receive subcutaneous (SC) mosunetuzumab.
Polatuzumab vedotin: Participants will receive IV polatuzumab vedotin.
Tocilizumab: Participants will receive IV tocilizumab as needed.
Rituximab: Participants will receive IV rituximab.
Study summary
This study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of intravenous (IV) or subcutaneous (SC) mosunetuzumab in combination with polatuzumab vedotin in participants with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). It will consist of a dose finding portion followed by an expansion phase for second line or later (2L+) participants with relapsed or refractory (R/R) DLBCL and 2L+ R/R FL. In addition, subcutaneous mosunetuzumab in combination with polatuzumab vedotin will be evaluated in participants with at least 2 prior lines of systemic therapy (3L+) for the treatment of R/R mantle cell lymphoma (MCL) and in participants with 2L+ R/R DLBCL.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Key Inclusion Criteria:
* ECOG PS of 0, 1, or 2
* Histologically confirmed FL, DLBCL, or MCL
* Must have received at least one prior systemic treatment regimen containing an anti-CD20-directed therapy for DLBCL or FL
* For MCL, participants must have received at least two prior systemic treatment regiments, which include 1) anti-CD20-directed therapy, 2) BTK inhibitor, and 3) anthracycline or bendamustine
* Relapsed to prior regimen(s) after having a documented history of response (complete response \[CR\], CR unconfirmed \[CRu\], or partial response \[PR\]) of \>/= 6 months in duration from completion of regimen(s); or, refractory to any prior regimen, defined as no response to the prior therapy, or progression within 6 months of completion of the last dose of therapy
* Measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as \> 1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as \> 1.0 cm in its longest dimension
* Adequate hematologic, renal, and hepatic function
Key Exclusion Criteria:
* Prior treatment with mosunetuzumab or other CD20-directed bispecific antibodies
* Prior treatment with polatuzumab vedotin
* Current \> Grade 1 peripheral neuropathy
* Prior use of any monoclonal antibody, radioimmunoconjugate or antibody-drug conjugate (ADC) within 4 weeks before first dose of study treatment
* 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 first dose of study treatment
* Treatment with radiotherapy within 2 weeks prior to the first dose of study treatment
* Autologous stem-cell transplantation (SCT) within 100 days prior to first study treatment administration
* Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days before first study treatment administration
* Prior allogeneic SCT
* Prior solid organ transplantation
* Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
* Patients with history of confirmed progressive multifocal leukoencephalopathy (PML)
* Current or past history of central nervous system (CNS) lymphoma or CNS disease
* History of autoimmune disease
Primary outcome measure(s)
Maximum Tolerated Dose (MTD) of Mosunetuzumab in Combination with Polatuzumab Vedotin — Cycle 1 to Cycle 2 (cycle length = 21 days)
Recommended Phase II Dose of Mosunetuzumab in Combination with Polatuzumab Vedotin — Cycle 1 to Cycle 2 (cycle length = 21 days)
Percentage of Participants with Adverse Events (AE) — Baseline through approximately 90 days after last study treatment
Best Objective Response Rate (ORR), Defined as CR or Partial Response (PR) at any Time, Based on PET-CT and/or CT Scan, as Determined by the Independent Review Committee (IRC) using Standard Criteria for NHL — Baseline up to approximately 60 months (assessed at screening and then every 3 months for the first year, then every 6 months until disease progression, start of new anti-cancer therapy, or withdrawal)
Trial sites (29)
Facility
City
Region
Status
University of Alabama at Birmingham School of Medicine
Birmingham
Alabama
City of Hope
Duarte
California
University of Colorado Hospital - Anschutz Cancer Pavilion
Aurora
Colorado
University of Miami Miller School of Medicine
Miami
Florida
Moffitt Cancer Center
Tampa
Florida
University of Michigan Hospital
Ann Arbor
Michigan
Karmanos Cancer Institute
Detroit
Michigan
New York University Langone Medical Center
New York
New York
Levine Cancer Institute
Charlotte
North Carolina
Penn State Milton S. Hershey Medical Center
Hershey
Pennsylvania
Fox Chase Cancer Center
Philadelphia
Pennsylvania
University of Pittsburgh - Hillman Cancer Center
Pittsburgh
Pennsylvania
Lifespan Cancer Institute
Providence
Rhode Island
University of Texas M.D. Anderson Cancer Center
Houston
Texas
Fred Hutchinson Cancer Research Center
Seattle
Washington
Medical College of Wisconsin, Froedtert Hospital;Nephrology Section
Milwaukee
Wisconsin
UZ Brussel
Brussels
Belgium
CH Jolimont - Lobbes (Jolimont)
Haine-Saint-Paul
Belgium
Clinique St Pierre asbl
Ottignies
Belgium
Hamilton Health Sciences - Juravinski Cancer Centre
Hamilton
Ontario
Jewish General Hospital
Montreal
Quebec
Saskatchewan Cancer Agency (SCA) - Saskatoon Cancer Centre (SCC)
Saskatoon
Saskatchewan
Institut Catala d Oncologia Hospital Duran i Reynals
Barcelona
Spain
Hospital de San Pedro de Alcantara
Cáceres
Spain
Hospital General Universitario Gregorio Marañon
Madrid
Spain
Hospital Infanta Leonor; Servicio de Hematologia
Madrid
Spain
Hospital Universitario Virgen Macarena; Servicio de Oncologia
Seville
Spain
Cambridge University Hospitals NHS Foundation Trust
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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