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

Last updated: April 8, 2025
Sponsor: Hoffmann-La Roche
Overall Status: Active - Not Recruiting

Phase

3

Condition

Non-hodgkin's Lymphoma

Hematologic Cancer

Lymphoma, B-cell

Treatment

Oxaliplatin

Tocilizumab

Rituximab

Clinical Study ID

NCT05171647
GO43643
  • Ages > 18
  • All Genders

Study Summary

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).

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

  • CD20+ aggressive lymphoma as determined by the local hemopathology laboratory fromthe following diagnoses by 2016 World Health Organization classification of lymphoidneoplasms: DLBCL, not otherwise specified (NOS); high-grade B-cell lymphoma (NOS ordouble/triple hit); transformed follicular lymphoma; follicular lymphoma Grade 3b

  • Have disease relapsed or refractory to at least one prior systemic therapy foraggressive non-Hodgkin's lymphoma (aNHL)

  • Participants who have received only one prior line of therapy must be ineligible forautologous stem cell transplant (ASCT)

  • Measurable disease

  • Adequate hepatic, hematologic, and renal function

  • Estimated creatinine clearance (CrCl) ≥ 30 mL/min by Cockroft-Gault method or otherinstitutional standard methods

  • Negative HIV test at screening. Participants with a positive HIV test at screeningare eligible provided that, prior to enrollment, they are stable on anti-retroviraltherapy for at least 4 weeks, have a CD4 count of at least 200 microliters, have anundetectable viral load, and have not had a history of opportunistic infectionattributable to AIDS within the last 12 months

Exclusion

Exclusion Criteria:

  • Pregnant or breast feeding, or intending to become pregnant during the study orwithin 3 months after the final dose of mosunetuzumab, 9 months after the final doseof polatuzumab vedotin, 12 months after the final dose of rituximab, 6 months afterthe final dose of gemcitabine, 9 months after the final dose of oxaliplatin, and 3months 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, orR-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 ofpolatuzumab vedotin; participants who received up to 2 doses of a polatuzumabvedotin-containing regimen as bridging to CAR-T therapy, and either has a documenteddisease control (stable disease, partial response, or complete response), or werenot 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-lymphomatreatment (except for alopecia and anorexia, or other toxicities not considered asafety risk for the participant per investigator's judgment)

  • Received anti-lymphoma treatments with monoclonal antibodies, radio-immunoconjugatesor antibody-drug conjugates (ADCs) within 4 weeks before the first dose of studytreatment

  • Treatment with any chemotherapeutic agent, or treatment with any other anti-lymphomaagent (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 studytreatment

  • ASCT within 100 days prior to the first study treatment administration

  • Prior treatment with chimeric antigen receptor (CAR) T cell therapy within 30 daysbefore 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 orinterpretation of results, with the exception of malignancies with a negligible riskof 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, orneurodegenerative disease. Participants with a history of stroke who have notexperienced a stroke or transient ischemic attack in the past 2 years and have noresidual neurologic deficits as judged by the investigator, or with a history ofepilepsy who have had no seizures in the past 2 years while not receiving anyanti-epileptic medications, are allowed

  • Significant cardiovascular disease such as New York Heart Association Class III orIV cardiac disease, myocardial infarction within the last 6 months, unstablearrhythmias, 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 6months 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 majorepisode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 2 weeks prior tothe 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 treatmentadministration

  • 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 firstdose of study treatment administration or anticipation that such a live, attenuatedvaccine 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

Study Design

Total Participants: 242
Treatment Group(s): 6
Primary Treatment: Oxaliplatin
Phase: 3
Study Start date:
April 25, 2022
Estimated Completion Date:
February 28, 2027

Connect with a study center

  • FUNDALEU

    Buenos Aires, C1114AAN
    Argentina

    Site Not Available

  • Fundaleu; Haematology

    Buenos Aires, C1114AAN
    Argentina

    Site Not Available

  • Hospital Aleman

    Buenos Aires, 1118
    Argentina

    Site Not Available

  • Instituto Alexander Fleming

    Buenos Aires, 1426
    Argentina

    Site Not Available

  • Hospital Aleman

    Ciudad Autonoma Buenos Aires, C1118AAT
    Argentina

    Site Not Available

  • Hospital Italiano de Buenos Aires

    Ciudad Autonoma Buenos Aires, C1181ACH
    Argentina

    Site Not Available

  • Hospital Italiano de Buenos Aires

    Ciudad Autónoma de Buenos Aires, C1181ACH
    Argentina

    Site Not Available

  • Hospital Erasto Gaertner

    Curitiba, Paraná 81520-060
    Brazil

    Site Not Available

  • Hospital das Clinicas - UFRGS

    Porto Alegre, Rio Grande Do Sul 90035-903
    Brazil

    Site Not Available

  • D'or Instituto de Pesquisa e Educação

    Sao Paulo, SP 04062-001
    Brazil

    Site Not Available

  • Hospital das Clínicas FMRP-USP

    Ribeirao Preto, São Paulo 14048-900
    Brazil

    Site Not Available

  • Hospital Sao Jose

    Sao Paulo, São Paulo 01323-030
    Brazil

    Site Not Available

  • D'or Instituto de Pesquisa e Educação

    São Paulo, 04062-001
    Brazil

    Site Not Available

  • Hamilton Health Sciences - Juravinski Cancer Centre

    Hamilton, Ontario L8V 5C2
    Canada

    Site Not Available

  • Princess Margaret Hospital

    Toronto, Ontario M5G 2M9
    Canada

    Site Not Available

  • Princess Margaret Hospital; Department of Med Oncology

    Toronto, Ontario M5G 2M9
    Canada

    Site Not Available

  • Chum Hopital Notre Dame

    Montreal, Quebec H2L 4M1
    Canada

    Site Not Available

  • Chum Hopital Notre Dame; Centre D'Oncologie

    Montreal, Quebec H2L 4M1
    Canada

    Site Not Available

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

    Saskatoon, Saskatchewan S7N 4H4
    Canada

    Site Not Available

  • Sichuan Cancer Hospital

    Chengdu, 610041
    China

    Site Not Available

  • Sichuan Cancer Hospital

    Chengdu City, 610041
    China

    Site Not Available

  • Fujian Medical University Union Hospital

    Fuzhou, 350001
    China

    Site Not Available

  • Fujian Medical University Union Hospital

    Fuzhou City, 350001
    China

    Site Not Available

  • Cancer Center, Sun Yat-sen University of Medical Sciences; Department of Medical Oncology

    Guangzhou, 510060
    China

    Site Not Available

  • Cancer Center, Sun Yat-sen University of Medical Sciences

    Guangzhou City, 510060
    China

    Site Not Available

  • Cancer Center, Sun Yat-sen University of Medical Sciences; Department of Medical Oncology

    Guangzhou City, 510060
    China

    Site Not Available

  • The First Affiliated Hospital of College of Medicine, Zhejiang University

    Hangzhou, 310003
    China

    Site Not Available

  • The Second Affiliated Hospital to Nanchang University

    Nanchang, 330006
    China

    Site Not Available

  • Tianjin Cancer Hospital

    Tianjin, 300060
    China

    Site Not Available

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

    Wuhan, 430030
    China

    Site Not Available

  • Henan Cancer Hospital

    Zhengzhou, 450008
    China

    Site Not Available

  • Soroka Medical Center

    Beer Sheva, 8410101
    Israel

    Site Not Available

  • Soroka Medical Center; Hematology Deptartment

    Beer Sheva, 8410101
    Israel

    Site Not Available

  • Meir Medical Center; Heamatology Dept

    Kfar Saba, 4428164
    Israel

    Site Not Available

  • Ichilov Sourasky Medical Center

    Tel Aviv, 6423906
    Israel

    Site Not Available

  • Ichilov Sourasky Medical Center; Heamatology

    Tel Aviv, 6423906
    Israel

    Site Not Available

  • Kyushu University Hospital

    Fukuoka, 812-8582
    Japan

    Site Not Available

  • Hokkaido University Hospital

    Hokkaido, 060-8648
    Japan

    Site Not Available

  • Kobe City Medical Center General Hospital

    Hyogo, 650-0047
    Japan

    Site Not Available

  • Tokai University Hospital

    Kanagawa, 259-1193
    Japan

    Site Not Available

  • Mie University Hospital

    Mie, 514-8507
    Japan

    Site Not Available

  • Tohoku University Hospital

    Miyagi, 980-8574
    Japan

    Site Not Available

  • Kindai University Hospital

    Osaka, 589-8511
    Japan

    Site Not Available

  • The Cancer Institute Hospital of JFCR

    Tokyo, 135-8550
    Japan

    Site Not Available

  • Yamagata University Hospital

    Yamagata, 990-9585
    Japan

    Site Not Available

  • Pusan National University Hospital

    Busan, 49241
    Korea, Republic of

    Site Not Available

  • Chungnam National University Hospital

    Daejeon, 35015
    Korea, Republic of

    Site Not Available

  • Samsung Medical Center

    Seoul, 06351
    Korea, Republic of

    Site Not Available

  • Seoul National University Hospital

    Seoul, 03080
    Korea, Republic of

    Site Not Available

  • Severance Hospital, Yonsei University Health System

    Seoul, 03722
    Korea, Republic of

    Site Not Available

  • Yeouido St. Mary's Hospital

    Seoul, 07345
    Korea, Republic of

    Site Not Available

  • Health Pharma Professional Research

    Cdmx, Mexico CITY (federal District) 03100
    Mexico

    Site Not Available

  • Health Pharma Professional Research

    Ciudad de México, Mexico CITY (federal District) 03100
    Mexico

    Site Not Available

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

    Ciudad de México, Mexico CITY (federal District) 11550
    Mexico

    Site Not Available

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

    Mexico, Mexico CITY (federal District) 06760
    Mexico

    Site Not Available

  • Hospital Universitario Dr. Jose E. Gonzalez

    Monterrey, Nuevo LEON 64460
    Mexico

    Site Not Available

  • Hospital Universitario Dr. Jose E. Gonzalez; Haematology

    Monterrey, Nuevo LEON 64460
    Mexico

    Site Not Available

  • Instituto Nacional de Cancerologia

    Distrito Federal, 14080
    Mexico

    Site Not Available

  • Instituto Nacional de Cancerologia; Oncology

    Distrito Federal, 14080
    Mexico

    Site Not Available

  • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

    Mexico,
    Mexico

    Site Not Available

  • Instituto Nacional de Cancerologia; Oncology

    Mexico City, 14080
    Mexico

    Site Not Available

  • Middlemore Clinical Trials

    Auckland,
    New Zealand

    Site Not Available

  • Instituto Regional de Enfermedades Neoplásicas del Sur

    Arequipa, 5154
    Peru

    Site Not Available

  • Instituto Regional de Enfermedades Neoplásicas del Sur; Centro de Inv. de Medicina Oncológica

    Arequipa, 5154
    Peru

    Site Not Available

  • Hospital Nacional Edgardo Rebagliati Martins, Servicio de Gastroenterologia

    Lima, 11
    Peru

    Site Not Available

  • Instituto Nacional de Enfermedades Neoplasicas

    Lima, 15038
    Peru

    Site Not Available

  • Oncosalud Sac

    Lima, 41
    Peru

    Site Not Available

  • Oncosalud Sac; Oncología

    Lima, 41
    Peru

    Site Not Available

  • Hospital De Alta Complejidad Virgen De La Puerta - Essalud; Oncology

    Trujillo, 13013
    Peru

    Site Not Available

  • Regional Clinical Hospital N.A. Semashko; Hematology

    Nizhny Novgorod, Niznij Novgorod 603126
    Russian Federation

    Site Not Available

  • Blokhin Cancer Research Center; Clinical Oncology

    Moscow, 115478
    Russian Federation

    Site Not Available

  • Penza Regional Oncology Dispensary

    Penza, 440071
    Russian Federation

    Site Not Available

  • St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta

    Saint-Petersburg, 197022
    Russian Federation

    Site Not Available

  • Chulalongkorn University Hospital

    Bangkok, 10330
    Thailand

    Site Not Available

  • Chulalongkorn University Hospital; Hematology

    Bangkok, 10330
    Thailand

    Site Not Available

  • Siriraj Hospital

    Bangkok, 10700
    Thailand

    Site Not Available

  • Siriraj Hospital; Division of Hematology, Department of Medicine

    Bangkok, 10700
    Thailand

    Site Not Available

  • Chiang Mai Uni Hospital

    Chiang Mai, 50200
    Thailand

    Site Not Available

  • Chiang Mai Uni Hospital; Division of Hematology,Dept of Medicine,Faculty of Medicine

    Chiang Mai, 50200
    Thailand

    Site Not Available

  • Srinagarind Hospital, Khon Kaen Uni

    Khon Kaen, 40002
    Thailand

    Site Not Available

  • Srinagarind Hospital, Khon Kaen Uni ; Dept of Medicine

    Khon Kaen, 40002
    Thailand

    Site Not Available

  • Chulalongkorn University Hospital; Hematology

    Pathum Wan, 10330
    Thailand

    Site Not Available

  • Ankara University Medical Faculty

    Ankara, 06100
    Turkey

    Site Not Available

  • Medipol Mega Üniversite Hastanesi Göztepe

    Istanbul, 34214
    Turkey

    Site Not Available

  • Dokuz Eylul Universitesi Tip Fakultesi

    Izmir, 35340
    Turkey

    Site Not Available

  • Anadolu Health Center

    Kocaeli, 41400
    Turkey

    Site Not Available

  • Anadolu Health Center; Heamathology Department

    Kocaeli, 41400
    Turkey

    Site Not Available

  • Dokuz Eylul Universitesi Tip Fakultesi

    Lzmir, 35340
    Turkey

    Site Not Available

  • Ondokuz Mayis Univ. Med. Fac.

    Samsun, 55139
    Turkey

    Site Not Available

  • Alaska Oncology & Hematology, LLC

    Anchorage, Alaska 99508
    United States

    Site Not Available

  • Ironwood cancer and research center

    Chandler, Arizona 85224
    United States

    Site Not Available

  • City of Hope Cancer Center

    Duarte, California 91010
    United States

    Site Not Available

  • City of Hope Cancer Center; Division of Medical Oncology & Experimental Therapeutics

    Duarte, California 91010
    United States

    Site Not Available

  • Kaiser Permanente - Irvine

    Irvine, California 92618
    United States

    Site Not Available

  • Cancer Blood and Specialty Clinic

    Los Alamitos, California 90720
    United States

    Site Not Available

  • USC School of Medicine

    Los Angeles, California 90033
    United States

    Site Not Available

  • University of Miami - Clinical Research Services

    Miami, Florida 33136
    United States

    Site Not Available

  • Investigative Clinical Research of Indiana, LLC

    Noblesville, Indiana 46062
    United States

    Site Not Available

  • St. Luke's Hospital

    Chesterfield, Missouri 63017
    United States

    Site Not Available

  • Levine Cancer Institute - Clincal Trials Administration

    Charlotte, North Carolina 28204
    United States

    Site Not Available

  • Rhode Island Hospital; Comprehensive Cancer Center

    Providence, Rhode Island 02903
    United States

    Site Not Available

  • Ascension Seton Infusion Center

    Austin, Texas 78712
    United States

    Site Not Available

  • MD Anderson Cancer Center

    Houston, Texas 77030
    United States

    Site Not Available

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