A Study to Evaluate the Safety and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With Polatuzumab Vedotin in B-Cell Non-Hodgkin Lymphoma

NCT ID: NCT03671018

Last Updated: 2024-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

422 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-25

Study Completion Date

2025-07-20

Brief Summary

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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.

Detailed Description

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Conditions

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B-cell Non-Hodgkin Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Finding

Participants will receive mosunetuzumab in combination with polatuzumab vedotin. Dose finding will be guided by the observed incidence of dose-limiting toxicities (DLTs) at each dose level.

Group Type EXPERIMENTAL

Mosunetuzumab (IV)

Intervention Type DRUG

Participants will receive intravenous (IV) mosunetuzumab.

Polatuzumab vedotin

Intervention Type DRUG

Participants will receive IV polatuzumab vedotin.

Tocilizumab

Intervention Type DRUG

Participants will receive IV tocilizumab as needed.

Mosunetuzumab + Polatuzumab Vedotin 2L+ R/R FL

Participants with at least one line of prior therapy (2L+) and that have relapsed or refractory (R/R) follicular lymphoma (FL) will receive mosunetuzumab + polatuzumab vedotin.

Group Type EXPERIMENTAL

Mosunetuzumab (IV)

Intervention Type DRUG

Participants will receive intravenous (IV) mosunetuzumab.

Polatuzumab vedotin

Intervention Type DRUG

Participants will receive IV polatuzumab vedotin.

Tocilizumab

Intervention Type DRUG

Participants will receive IV tocilizumab as needed.

Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCL

2L+ participants with R/R diffuse large B-cell lymphoma will receive mosunetuzumab + polatuzumab vedotin.

Group Type EXPERIMENTAL

Mosunetuzumab (IV)

Intervention Type DRUG

Participants will receive intravenous (IV) mosunetuzumab.

Polatuzumab vedotin

Intervention Type DRUG

Participants will receive IV polatuzumab vedotin.

Tocilizumab

Intervention Type DRUG

Participants will receive IV tocilizumab as needed.

Rituximab

Intervention Type DRUG

Participants will receive IV rituximab.

Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCL

Participants with at least 2 lines of prior therapy (3L+) will receive subcutaneous (SC) mosunetuzumab + polatuzumab vedotin.

Group Type EXPERIMENTAL

Mosunetuzumab (SC)

Intervention Type DRUG

Participants will receive subcutaneous (SC) mosunetuzumab.

Polatuzumab vedotin

Intervention Type DRUG

Participants will receive IV polatuzumab vedotin.

Tocilizumab

Intervention Type DRUG

Participants will receive IV tocilizumab as needed.

Mosunetuzumab SC + Polatuzumab Vedotin 2L+R/R DLBCL

2L+ participants with R/R DLBCL will receive SC mosunetuzumab and polatuzumab vedotin.

Group Type EXPERIMENTAL

Mosunetuzumab (SC)

Intervention Type DRUG

Participants will receive subcutaneous (SC) mosunetuzumab.

Polatuzumab vedotin

Intervention Type DRUG

Participants will receive IV polatuzumab vedotin.

Tocilizumab

Intervention Type DRUG

Participants will receive IV tocilizumab as needed.

Interventions

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Mosunetuzumab (IV)

Participants will receive intravenous (IV) mosunetuzumab.

Intervention Type DRUG

Mosunetuzumab (SC)

Participants will receive subcutaneous (SC) mosunetuzumab.

Intervention Type DRUG

Polatuzumab vedotin

Participants will receive IV polatuzumab vedotin.

Intervention Type DRUG

Tocilizumab

Participants will receive IV tocilizumab as needed.

Intervention Type DRUG

Rituximab

Participants will receive IV rituximab.

Intervention Type DRUG

Other Intervention Names

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BTCT4465A

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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University of Alabama at Birmingham School of Medicine

Birmingham, Alabama, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

University of Colorado Hospital - Anschutz Cancer Pavilion

Aurora, Colorado, United States

Site Status

University of Miami Miller School of Medicine

Miami, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

University of Michigan Hospital

Ann Arbor, Michigan, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

New York University Langone Medical Center

New York, New York, United States

Site Status

Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh - Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Lifespan Cancer Institute

Providence, Rhode Island, United States

Site Status

University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

Medical College of Wisconsin, Froedtert Hospital;Nephrology Section

Milwaukee, Wisconsin, United States

Site Status

UZ Brussel

Brussels, , Belgium

Site Status

CH Jolimont - Lobbes (Jolimont)

Haine-Saint-Paul, , Belgium

Site Status

Clinique St Pierre asbl

Ottignies, , Belgium

Site Status

Hamilton Health Sciences - Juravinski Cancer Centre

Hamilton, Ontario, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Saskatchewan Cancer Agency (SCA) - Saskatoon Cancer Centre (SCC)

Saskatoon, Saskatchewan, Canada

Site Status

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, , Spain

Site Status

Hospital de San Pedro de Alcantara

Cáceres, , Spain

Site Status

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Site Status

Hospital Infanta Leonor; Servicio de Hematologia

Madrid, , Spain

Site Status

Hospital Universitario Virgen Macarena; Servicio de Oncologia

Seville, , Spain

Site Status

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

Site Status

Plymouth Hospitals NHS Trust; Pharmacy Dept

Plymouth, , United Kingdom

Site Status

Countries

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United States Belgium Canada Spain United Kingdom

References

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Budde LE, Olszewski AJ, Assouline S, Lossos IS, Diefenbach C, Kamdar M, Ghosh N, Modi D, Sabry W, Naik S, Mehta A, Nakhoda SK, Smith SD, Dorritie K, Jia T, Pham S, Huw LY, Jing J, Wu H, Ead WS, To I, Batlevi CL, Wei MC, Chavez JC. Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. Nat Med. 2024 Jan;30(1):229-239. doi: 10.1038/s41591-023-02726-5. Epub 2023 Dec 10.

Reference Type DERIVED
PMID: 38072960 (View on PubMed)

Other Identifiers

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2018-001141-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO40516

Identifier Type: -

Identifier Source: org_study_id