An Open-Label Study Comparing Glofitamab and Polatuzumab Vedotin + Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone Versus Pola-R-CHP in Previously Untreated Patients With Large B-Cell Lymphoma

Large B-Cell Lymphoma Clinical Trial

Official title:

A Phase III, Multicenter, Randomized, Open-Label Study Comparing the Efficacy and Safety of Glofitamab (RO7082859) in Combination With Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (Pola-R-CHP) Versus Pola-R-CHP in Previously Untreated Patients With Large B-Cell Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06047080
• Other study ID #: GO44145
• Status: Recruiting
• Phase: Phase 3
• Start date: September 18, 2023
• Est. completion date: February 28, 2029

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: GO44145 https://forpatients.roche.com
• Phone: 888-662-6728
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the efficacy and safety of glofitamab in combination with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) vs Pola-R-CHP in participants with previously untreated CD20-positive large B-cell lymphoma (LBCL).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1130
• Est. completion date: February 28, 2029
• Est. primary completion date: June 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Previously untreated participants with CD20-positive LBCL
• Ability to provide tumor tissue
• International prognostic index (IPI) score 2-5
• Eastern cooperative oncology group (ECOG) performance status of 0, 1, or 2
• At least one bi-dimensionally measurable lesion, defined as > 1.5 cm in its longest dimension as measured by CT or MRI
• Left ventricular ejection fraction (LVEF) >/=50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
• Adequate hematologic function
• Negative HIV test at screening with exceptions as defined by the protocol
• Negative SARS-CoV-2 antigen or PCR test

Exclusion Criteria:

• Contraindication to any of the individual components of Pola-R-CHP or glofitamab, including prior receipt of anthracyclines, or history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, or known sensitivity or allergy to murine products
• Prior solid organ transplantation
• Participants receiving systemic immunosuppressive agent such as, but not limited to cyclosporin, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 4 weeks prior to first dose of study treatment
• Current Grade > 1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease
• History of indolent lymphoma (e.g., Follicular Lymphoma, Marginal Zone Lymphoma, Waldenstrom macroglobulinemia)
• Current diagnosis of the following: Follicular lymphoma grade 3B; transformations of indolent B-cell lymphomas (e.g., de novo transformed follicular lymphoma); mediastinal grey zone lymphoma; primary mediastinal (thymic) large B-cell lymphoma; Burkitt lymphoma; primary large B-cell lymphoma of immune-privileged sites (encompassing primary diffuse large B-cell lymphoma of the CNS, primary large B-cell lymphoma of the vitreoretina and primary large B-cell lymphoma of the testis); primary effusion DLBCL; and primary cutaneous DLBCL, leg type
• Primary or secondary CNS lymphoma at the time of recruitment or history of CNS lymphoma
• Prior treatment with systemic immunotherapeutic agents
• Prior use of any monoclonal antibody for the purposes of treating cancer within 3 months of the start of Cycle 1
• Any investigational therapy for the purposes of treating cancer within 28 days prior to the start of Cycle 1
• Prior radiotherapy to the mediastinal/pericardial region
• Prior therapy for LBCL, with the exception of corticosteriods
• Corticosteroid use > 50 mg/day of prednisone or equivalent, for purposes other than lymphoma symptom control
• History of other malignancy that could affect compliance with the protocol or interpretation of results
• Significant or extensive history of cardiovascular disease
• Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis
• Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Known or suspected chronic active Epstein-Barr viral infection
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Active autoimmune disease which is not well controlled by therapy
• Clinically significant liver disease
• Live, attenuated vaccine within 4 weeks before study treatment infusion on Day 1 of Cycle 1 or anticipation that such a live, attenuated vaccine will be required during the study. Live vaccines during the study and until participants B cells recover are prohibited
• Any active infection within 7 days prior to Cycle 1 Day 1 that would impact participant safety
• Suspected active or latent tuberculosis
• Positive test results for chronic hepatitis B infection, hepatitis C, or the human T-lymphotropic virus type 1 (HTLV-1)
• History of progressive multifocal leukoencephalopathy

Related Conditions & MeSH terms

• Large B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell

Intervention

Drug:
• Glofitamab
Participants will receive intravenous (IV) glofitamab
• Polatuzumab vedotin
Participants will receive IV polatuzumab vedotin in combination with R-CHP
• Rituximab
Participants will receive IV rituximab
• Cyclophosphamide
Participants will receive cyclophosphamide as part of CHP chemotherapy
• Doxorubicin
Participants will receive IV doxorubicin
• Prednisone
Participants will receive oral prednisone as part of CHP chemotherapy

Locations

Country	Name	City	State
Argentina	Fundaleu; Haematology	Buenos Aires
Argentina	Hospital Aleman de Buenos Aires; Servicio de Oncologia	Buenos Aires
Argentina	Instituto Alexander Fleming	Buenos Aires
Argentina	Sanatorio Allende; Haematology	Cordoba
Australia	Flinders Medical Centre; Dept of Haematology	Bedford Park	South Australia
Australia	Eastern Health	Box Hill	Victoria
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Townsville Hospital; Haematology and Oncology	Douglas	Queensland
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Barwon Health	Geelong	Victoria
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Peter Maccallum Cancer Centre	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Prince of Wales Hospital- Department of Hematology	Randwick	New South Wales
Australia	Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology	Woolloongabba	Queensland
Belgium	Institut Jules Bordet	Anderlecht
Belgium	UZ Brussel	Brussel
Belgium	UZ Antwerpen	Edegem
Belgium	UZ Gent	Gent
Belgium	AZ Groeninge	Kortrijk
Belgium	CHU Sart-Tilman	Liège
Brazil	Hospital Erasto Gaertner	Curitiba	PR
Brazil	Instituto D'Or Pesquisa e Ensino	Sao Paulo	SP
Canada	Centre Hospitalier de l'Universite de Montreal (CHUM)	Montreal	Quebec
Canada	CHA Hopital de I enfant-Jesus	Quebec City	Quebec
Canada	BC Cancer ? Victoria	Victoria	British Columbia
China	Beijing Cancer Hospital	Beijing
China	Peking University Third Hospital	Beijing
China	The First Hospital of Jilin University	Changchun City
China	Hunan Cancer Hospital	Changsha CITY
China	Sichuan Provincial People's Hospital	Chengdu
China	West China Hospital, Sichuan University	Chengdu
China	Second Affiliated Hospital of Third Military Medical University	Chongqing
China	Fujian Cancer Hospital	Fuzhou
China	Southern Medical University Nanfang Hospital	Guangdong Province Guangzhou City
China	Sun yat-sen University Cancer Center; Internal Medicine of Oncology	Guangzhou
China	Zhujiang Hospital, Southern Medical University	Guangzhou
China	Harbin Medical University Cancer Hospital	Harbin
China	Anhui Province Cancer Hospital	Hefei City
China	Shandong Cancer Hospital	Jinan
China	Jiangxi Cancer Hospital	Nanchang City
China	Jiangsu Cancer Hospital	Nanjing City
China	Guangxi Cancer Hospital of Guangxi Medical University	Nanning City
China	Fudan University Shanghai Cancer Center	Shanghai City
China	First Hospital of China Medical University	Shenyang
China	Shengjing Hospital of China Medical University	Shenyang City
China	First Affiliated Hospital of Soochow University	Suzhou
China	Tianjin Cancer Hospital	Tianjin
China	Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences	Tianjin City
China	Tongji Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
China	First Affiliated Hospital of Medical College of Xi'an Jiaotong University	Xi'an
China	The First Affiliated Hospital of Xiamen University	Xiamen
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou
Denmark	Aalborg Universitetshospital; Hæmatologisk afdeling	Aalborg
Denmark	Aarhus Universitetshospital Skejby; Blodsygdomme	Aarhus N
Denmark	Regionshospitalet Gødstrup; Medicinsk Afdeling, Klinik for Blodsygdomme	Herning
France	CHRU de Lille - Hopital Claude Huriez	Lille
France	Hospices Civils de Lyon	Lyon
France	Institut Paoli Calmettes	Marseille
France	CHU Montpellier	Montpellier
France	CHU de Nantes - Hotel Dieu	Nantes
France	CHU de Bordeaux	Pessac
France	CHU DE RENNES - CHU Pontchaillou; Service d'Hématologie Clinique Adulte	Rennes
France	Centre Henri Becquerel	Rouen
France	CHU Strasbourg Hôpital Hautepierre	Strasbourg
France	IUCT Oncopole	Toulouse
Germany	Charité Universitätsmedizin Berlin; Hämatologie/Onkologie und Tumorimmunologie	Berlin
Germany	Staedisches Klinikum Brandenburg	Brandenburg an der Havel
Germany	Klinikum Chemnitz gGmbH, Klinik f. Innere Medizin III	Chemnitz
Germany	Universitätsklinikum Erlangen, Medizinische Klinik 5, Hämatologie und Internistische Onkologie	Erlangen
Germany	Universitätsklinikum Essen; Klinik für Hämatologie	Essen
Germany	UKE Universitätsklinikum Hamburg-Eppendorf; II. Medizinische Klinik und Poliklinik	Hamburg
Germany	Städtisches Krankenhaus Kiel GmbH	Kiel
Germany	Universitätsklinikum Köln; Klinik I für Innere Medizin - Onkologie, Hämatologie	Koeln
Germany	Universitaetsklinikum Schleswig Holstein - Campus Luebeck; Haematologie, Onkologie	Luebeck
Germany	Otto von Guericke Uni Magdeburg Uniklinik; Hämatologie/Onkologie	Magdeburg
Germany	Klinikum rechts der Isar der TU München, III. Medizinische Klinik; Hämatologie und intern. Onkologie	München
Germany	Universitätsklinikum Münster; Med. Klinik A; Hämatologie, Hämostaseologie, Onkologie & Pneumologie	Münster
Germany	Klinikum Ernst von Bergman; Klinik für Hämatologie, Onkologie und Palliativmedizin	Potsdam
Germany	Klinikum Stuttgart Katharinenhospital; Klinik f. Hämatologie, Onkologie u. Palliativmedizin	Stuttgart
Germany	Universitätsklinikum Ulm; Medizinische Uni-Klinik III Abt. Innere Medizin III Hämatologie u. Onkolo.	Ulm
Germany	Universitätsklinikum Würzburg; Medizinische Klinik und Poliklinik II; Hämatologie / Onkologie	Würzburg
Italy	ASST PAPA GIOVANNI XXIII; Ematologia	Bergamo	Lombardia
Italy	Policlinico S.Orsola-Malpighi;Istituto di Ematologia "Seragnoli"	Bologna	Emilia-Romagna
Italy	A. O. U. Policlinico G. Rodolico; Ematologia	Catania	Sicilia
Italy	A.O. Universitaria S. Martino Di Genova; Ematologia 1	Genova	Liguria
Italy	Fond. IRCCS Istituto Nazionale Tumori; S. C. Ematologia	Milano	Lombardia
Italy	A.O. Universitaria Policlinico Di Modena; Ematologia	Modena	Emilia-Romagna
Italy	Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica	Napoli	Campania
Italy	USL 4 di Prato - Nuovo Ospeale di Prato	Prato	Toscana
Italy	Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia	Rozzano	Lombardia
Italy	Ospedale San Bortolo; UOC di Ematologia'	Vicenza	Veneto
Japan	Aichi Cancer Center	Aichi
Japan	Kobe City Medical Center General Hospital	Hyogo
Japan	Tokai University Hospital	Kanagawa
Japan	University Hospital Kyoto Prefectural University of Medicine	Kyoto
Japan	Kindai University Hospital	Osaka
Japan	National Cancer Center Hospital	Tokyo
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	Yamagata University Hospital	Yamagata
Korea, Republic of	Inje university Haeundae Paik Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Chonnam National University Hwasun Hospital	Jeollanam-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St Mary's Hospital	Seoul
Korea, Republic of	Severance Hospital; Yonsei University Health System	Seoul
Korea, Republic of	Yeouido St. Mary's Hospital	Seoul
Mexico	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)
Mexico	Hospital General de Mexico	Mexico	Tlaxcala
Mexico	Inst. Nacional de Cancerologia; Investigacion Clinica	Mexico City	Mexico CITY (federal District)
Poland	Szpital Specjalistyczny Podkarpacki O?rodek Onkologiczny	Brzozów
Poland	Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii	Gda?sk
Poland	Pratia Onkologia Katowice	Katowice
Poland	?wi?tokrzyskie Centrum Onkologii SPZOZ; Klinika Hematologii i Transplantacji Szpiku	Kielce
Poland	PRATIA MCM Kraków	Kraków
Poland	Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku	Wroc?aw
Spain	Hospital Universitari Vall d'Hebron; Servicio de Hematologia	Barcelona
Spain	Clinica Universidad de Navarra Madrid; Servicio de Hematología	Madrid
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Hematología	Madrid
Spain	Clinica Universitaria de Navarra; Servicio de Hematologia	Pamplona	Navarra
Spain	Hospital Quiron de Madrid; Servicio de Hematologia	Pozuelo de Alarcon	Madrid
Spain	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Hematologia	Santiago de Compostela	LA Coruña
Spain	Hospital Universitario Virgen del Rocio; Servicio de Hematologia	Sevilla
Spain	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia
Taiwan	CHANG GUNG MEDICAL FOUNDATION - CHAI YI;HEMATOLOGY and ONCOLOGY	Chai Yi
Taiwan	Chang Gung Medical Foundation - Kaohsiung; Oncology; Division of Hematology-Oncology	Kaoisung
Taiwan	E-Da Cancer Hospital; Hematology- Oncology Department	Kaoshiung
Taiwan	China Medical University Hospital; Oncology and Hematology	Taichung
Taiwan	Chi-Mei Hospital, Liouying	Tainan
Taiwan	National Taiwan University Hospital; Internal Medicince	Taipei
Turkey	Abdurrahman Yurtarslan Onkoloji Training and Research Hospital	Ankara
Turkey	Ankara Universitesi Tip Fakultesi Hastaneleri - Cebeci Hastanesi	Ankara
Turkey	Istanbul VKV American Hospital; Haematology	Istanbul
Turkey	Marmara University Pendik Training and Research Hospital	Istanbul
Turkey	Kocaeli Univesity Medical Faculty; Department of Internal Medicine	Izmit
United Kingdom	Barnet Hospital; ROYAL FREE LONDON NHS FOUNDATION TRUST	Barnet
United Kingdom	BLACKPOOL VICTORIA HOSPITAL; Clinical Research Centre	Blackpool
United Kingdom	East Kent Hospitals University NHS Foundation Trust	Canterbury
United Kingdom	Royal Devon and Exeter Hospital; Oncology	Exeter
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Leeds Teaching Hosp NHS Trust;St James's Institute of Onc	Leeds
United Kingdom	Guy'S Hospital; Oncology Unit	London
United Kingdom	University College London Hospitals NHS Foundation Trust - University College Hospital	London
United Kingdom	Newcastle University; Northern Institute For Cancer Research Paul O'gorman Building	Newcastle
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Churchill Hospital - Oxford Cancer & Haematology Centre; Department of Oncology	Oxford
United States	Alaska Oncology & Hematology, LLC	Anchorage	Alaska
United States	Medstar Franklin Square Medical Center	Baltimore	Maryland
United States	St. Luke's Hospital	Chesterfield	Missouri
United States	University of California, San Francisco-Fresno	Fresno	California
United States	Avera Cancer Institute	Sioux Falls	South Dakota

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Denmark,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS) as determined by Independent Review Facility (IRF)		From randomization to the first occurrence of disease progression or relapse, or death due to any cause, whichever occurs first (up to approximately 65 months)
Secondary	PFS as determined by the investigator		From randomization to the first occurrence of disease progression or relapse or death from any cause, whichever occurs first (up to approximately 65 months)
Secondary	PFS as determined by the investigator and IRF for participants with international prognostic index (IPI) 3-5		From randomization to the first occurrence of disease progression or relapse or death from any cause, whichever occurs first (up to 65 months)
Secondary	Event-free survival efficacy causes (EFSeff)		From randomization to the earliest occurrence of disease progression or relapse; death due to any cause; initiation of new anti-lymphoma treatment; or positive biopsy for residual disease after treatment completion (up to approximately 65 months)
Secondary	Complete response (CR) rate		At the end of treatment (up to approximately 65 months)
Secondary	Objective response rate (ORR)		At treatment completion or discontinuation (up to approximately 65 months)
Secondary	Overall survival (OS)		From randomization to death from any cause (up to approximately 65 months)
Secondary	Duration of response (DOR)		From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 65 months)
Secondary	Duration of complete response (DOCR)		From the first occurrence of a documented complete response (CR) to disease progression or death, whichever occurs first (up to approximately 65 months)
Secondary	Disease-free survival (DFS)		From a documented CR at the end of treatment to disease progression or death, whichever occurs first (up to approximately 65 months)
Secondary	Serum concentration of glofitamab		Up to approximately 65 months
Secondary	Incidence of anti-drug antibodies (ADAs)		Baseline up to approximately 65 months
Secondary	Proportion of participants experiencing a clinically meaningful improvement in physical functioning and fatigue (EORTC QLQ-C30) and lymphoma symptoms (FACT-Lym LymS)		Up to approximately 65 months
Secondary	Time to deterioration in physical functioning and fatigue (EORTC QLQ-C30) and lymphoma symptoms (FACT-Lym LymS)		Up to approximately 65 months
Secondary	Percentage of Participants with Adverse Events (AEs)		From randomization to the end of study (up to approximately 65 months)