A Study Evaluating Efficacy and Safety of Mosunetuzumab in Combination With Polatuzumab Vedotin Compared to Rituximab in Combination With Gemcitabine Plus Oxaliplatin in Participants With Relapsed or Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma

NCT ID: NCT05171647

Last Updated: 2025-11-12

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

PHASE3

Total Enrollment

242 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-25

Study Completion Date

2027-02-28

Brief Summary

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This study will assess the efficacy and safety of mosunetuzumab in combination with polatuzumab vedotin (M+P) in participants with relapsed or refractory (R/R) diffuse-large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, transformed follicular lymphoma (trFL) and FL Grade 3B (FL3B) in comparison with a commonly used regimen in this participant population, rituximab, gemcitabine and oxaliplatin (R-GemOx).

Detailed Description

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Conditions

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Non-Hodgkin Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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M+P (Arm A)

Participants will receive subcutaneous (SC) mosunetuzumab plus intravenous (IV) polatuzumab vedotin (M+P). Mosunetuzumab will be administered on Days 1, 8, and 15 of Cycle 1, and thereafter on Day 1 of Cycles 2-8. Polatuzumab vedotin will be administered on Day 1 of each cycle up to Cycle 6. Cycle length = 21 days.

Group Type EXPERIMENTAL

Mosunetuzumab

Intervention Type DRUG

Participants will receive SC mosunetuzumab on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-8 (cycle length = 21 days).

Polatuzumab vedotin

Intervention Type DRUG

Participants will receive IV polatuzumab vedotin every three weeks (Q3W) for 6 cycles (cycle length = 21 days).

Tocilizumab

Intervention Type DRUG

Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events.

R-GemOx (Arm B)

Participants will receive IV rituximab, IV gemcitabine, and IV oxaliplatin (R-GemOx) on Day 1 of each cycle for 8 cycles. Cycle length = 14 days.

Group Type ACTIVE_COMPARATOR

Rituximab

Intervention Type DRUG

Participants will receive IV rituximab on Day 1 of each cycle for 8 cycles (cycle length = 14 days).

Gemcitabine

Intervention Type DRUG

Participants will receive IV gemcitabine on Day 1 of each cycle for 8 cycles (cycle length = 14 days).

Oxaliplatin

Intervention Type DRUG

Participants will receive IV oxaliplatin on Day 1 of each cycle for 8 cycles (cycle length = 14 days).

Interventions

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Mosunetuzumab

Participants will receive SC mosunetuzumab on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-8 (cycle length = 21 days).

Intervention Type DRUG

Polatuzumab vedotin

Participants will receive IV polatuzumab vedotin every three weeks (Q3W) for 6 cycles (cycle length = 21 days).

Intervention Type DRUG

Tocilizumab

Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events.

Intervention Type DRUG

Rituximab

Participants will receive IV rituximab on Day 1 of each cycle for 8 cycles (cycle length = 14 days).

Intervention Type DRUG

Gemcitabine

Participants will receive IV gemcitabine on Day 1 of each cycle for 8 cycles (cycle length = 14 days).

Intervention Type DRUG

Oxaliplatin

Participants will receive IV oxaliplatin on Day 1 of each cycle for 8 cycles (cycle length = 14 days).

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
* CD20+ aggressive lymphoma as determined by the local hemopathology laboratory from the following diagnoses by 2016 World Health Organization classification of lymphoid neoplasms: DLBCL, not otherwise specified (NOS); high-grade B-cell lymphoma (NOS or double/triple hit); transformed follicular lymphoma; follicular lymphoma Grade 3b
* Have disease relapsed or refractory to at least one prior systemic therapy for aggressive non-Hodgkin's lymphoma (aNHL)
* Participants who have received only one prior line of therapy must be ineligible for autologous stem cell transplant (ASCT)
* Measurable disease
* Adequate hepatic, hematologic, and renal function
* Estimated creatinine clearance (CrCl) ≥ 30 mL/min by Cockroft-Gault method or other institutional standard methods
* Negative HIV test at screening. Participants with a positive HIV test at screening are eligible provided that, prior to enrollment, they are stable on anti-retroviral therapy for at least 4 weeks, have a CD4 count of at least 200 microliters, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months

Exclusion Criteria

* Pregnant or breast feeding, or intending to become pregnant during the study or within 3 months after the final dose of mosunetuzumab, 9 months after the final dose of polatuzumab vedotin, 12 months after the final dose of rituximab, 6 months after the final dose of gemcitabine, 9 months after the final dose of oxaliplatin, and 3 months after the final dose of tocilizumab, as applicable
* Inability to comply with protocol-mandated activity restrictions
* Prior treatment with mosunetuzumab or other CD-20-directed bispecific antibodies, or R-GemOx or Gem-Ox
* Prior treatment with polatuzumab vedotin, with the following exceptions: participants who have a documented response (partial response or complete response) to polatuzumab vedotin and an absence of PD within 12 months from the last dose of polatuzumab vedotin; participants who received up to 2 doses of a polatuzumab vedotin-containing regimen as bridging to CAR-T therapy, and either has a documented disease control (stable disease, partial response, or complete response), or were not assessed for response following treatment with polatuzumab vedotin
* Contraindication to any component of the study treatment
* Grade \> 1 peripheral neuropathy
* Participants with Grade \> 1 persistent toxicity related to prior anti-lymphoma treatment (except for alopecia and anorexia, or other toxicities not considered a safety risk for the participant per investigator's judgment)
* Received anti-lymphoma treatments with monoclonal antibodies, radio-immunoconjugates or antibody-drug conjugates (ADCs) within 4 weeks before the first dose of study treatment
* Treatment with any chemotherapeutic agent, or treatment with any other anti-lymphoma agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to the first dose of study treatment
* Treatment with radiotherapy within 2 weeks prior to the first dose of study treatment
* ASCT within 100 days prior to the first study treatment administration
* Prior treatment with chimeric antigen receptor (CAR) T cell therapy within 30 days before the first study treatment administration
* Prior allogenic stem cell transplant (SCT)
* Have had a solid organ transplantation
* Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
* History of confirmed progressive multifocal leukoencephalopathy
* History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombination antibody-related fusion proteins)
* History of other malignancy that could affect compliance with the protocol or interpretation of results, with the exception of malignancies with a negligible risk of metastasis or death
* Currently have or have had a past history of central nervous system (CNS) involvement of lymphoma
* Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. Participants with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurologic deficits as judged by the investigator, or with a history of epilepsy who have had no seizures in the past 2 years while not receiving any anti-epileptic medications, are allowed
* Significant cardiovascular disease such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina
* Significant active pulmonary disease
* Participants with active symptoms of interstitial lung disease and/or pneumonitis, or those with a history of interstitial lung disease and/or pneumonitis within 6 months prior to the first dose of study treatment
* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of the nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 2 weeks prior to the first study treatment administration
* Known or suspected chronic active Epstein-Barr virus (EBV) infection
* Recent major surgery within 4 weeks prior to the first study treatment administration
* Positive test results for chronic hepatitis B infection
* Acute or chronic hepatitis C virus (HCV) infection
* Have been administered a live, attenuated vaccine within 4 weeks before the first dose of study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study
* Participants who have positive SARS-CoV-2 test within 7 days prior to enrollment (rapid antigen test result is acceptable)
* History of autoimmune disease
* Received investigational therapy, whether or not intended for lymphoma treatment, within 7 days prior to initiation of study treatment
* Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis
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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City of Hope Cancer Center

Duarte, California, United States

Site Status

St. Luke's Hospital

Chesterfield, Missouri, United States

Site Status

Ascension Seton Infusion Center

Austin, Texas, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Hospital Aleman

Buenos Aires, , Argentina

Site Status

Instituto Alexander Fleming

Buenos Aires, , Argentina

Site Status

FUNDALEU

Buenos Aires, , Argentina

Site Status

Hospital Italiano de Buenos Aires

Ciudad Autonoma Buenos Aires, , Argentina

Site Status

Hospital Erasto Gaertner

Curitiba, Paraná, Brazil

Site Status

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Hospital das Clínicas FMRP-USP

Ribeirão Preto, São Paulo, Brazil

Site Status

Hospital Sao Jose

São Paulo, São Paulo, Brazil

Site Status

D'or Instituto de Pesquisa e Educação

São Paulo, , Brazil

Site Status

Hamilton Health Sciences - Juravinski Cancer Centre

Hamilton, Ontario, Canada

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Chum Hopital Notre Dame

Montreal, Quebec, Canada

Site Status

Sichuan Cancer Hospital

Chengdu, , China

Site Status

Fujian Medical University Union Hospital

Fuzhou, , China

Site Status

Cancer Center, Sun Yat-sen University of Medical Sciences

Guangzhou, , China

Site Status

Tianjin Cancer Hospital

Tianjin, , China

Site Status

Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech

Wuhan, , China

Site Status

Henan Cancer Hospital

Zhengzhou, , China

Site Status

Soroka Medical Center

Beersheba, , Israel

Site Status

Ichilov Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Kyushu University Hospital

Fukuoka, , Japan

Site Status

Hokkaido University Hospital

Hokkaido, , Japan

Site Status

Tohoku University Hospital

Miyagi, , Japan

Site Status

Kindai University Hospital

Osaka, , Japan

Site Status

The Cancer Institute Hospital of JFCR

Tokyo, , Japan

Site Status

Yamagata University Hospital

Yamagata, , Japan

Site Status

Health Pharma Professional Research

Mexico City, Mexico CITY (federal District), Mexico

Site Status

Superare Centro de Infusion S.A. de C.V.

Mexico City, Mexico CITY (federal District), Mexico

Site Status

Hospital Universitario Dr. Jose E. Gonzalez

Monterrey, Nuevo León, Mexico

Site Status

Instituto Nacional de Cancerologia

Distrito Federal, , Mexico

Site Status

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

México, , Mexico

Site Status

Middlemore Clinical Trials

Auckland, , New Zealand

Site Status

Instituto Regional de Enfermedades Neoplásicas del Sur

Arequipa, , Peru

Site Status

Oncosalud Sac

Lima, , Peru

Site Status

Pusan National University Hospital

Busan, , South Korea

Site Status

Chungnam National University Hospital

Daejeon, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Yeouido St. Mary's Hospital

Seoul, , South Korea

Site Status

Chulalongkorn University Hospital

Bangkok, , Thailand

Site Status

Siriraj Hospital

Bangkok, , Thailand

Site Status

Chiang Mai Uni Hospital

Chiang Mai, , Thailand

Site Status

Srinagarind Hospital, Khon Kaen Uni

Khon Kaen, , Thailand

Site Status

Ankara University Medical Faculty

Ankara, , Turkey (Türkiye)

Site Status

Medipol Mega Üniversite Hastanesi Göztepe

Istanbul, , Turkey (Türkiye)

Site Status

Anadolu Health Center

Kocaeli, , Turkey (Türkiye)

Site Status

Dokuz Eylul Universitesi Tip Fakultesi

Lzmir, , Turkey (Türkiye)

Site Status

Countries

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Russia United States Argentina Brazil Canada China Israel Japan Mexico New Zealand Peru South Korea Thailand Turkey (Türkiye)

References

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Budde LE, Zhang H, Kim WS, Maruyama D, Rego EM, Norasetthada L, Hong H, Ozcan M, Jeon YW, Cordeiro de Farias DL, Fogliatto LM, Pavlovsky A, Goto H, Olszewski AJ, Shah N, Hu B, Yin S, Wu H, To I, Ead WS, Ashby J, Janousek M, Pham S, Wang J, Kwan A, Batlevi CL, Wei MC, Westin J. Mosunetuzumab plus polatuzumab vedotin in transplant-ineligible refractory/relapsed large B-cell lymphoma: primary results of the phase 3 SUNMO trial. J Clin Oncol. 2025 Oct 2:101200JCO2501957. doi: 10.1200/JCO-25-01957. Online ahead of print.

Reference Type DERIVED
PMID: 41037766 (View on PubMed)

Other Identifiers

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GO43643

Identifier Type: -

Identifier Source: org_study_id