A Study to Evaluate Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma

Lymphoma Clinical Trial

— GLOBRYTE  

Official title:

A Phase III, Open-Label, Multicenter Randomized Study Evaluating Glofitamab as a Single Agent Versus Investigator's Choice in Patients With Relapsed/Refractory Mantle Cell Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06084936
• Other study ID #: GO43878
• Status: Recruiting
• Phase: Phase 3
• Start date: October 22, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: GO43878 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 evaluate the efficacy of glofitamab monotherapy compared with an investigator's choice of either rituximab plus bendamustine (BR), or lenalidomide with rituximab (R-Len) in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 182
• Est. completion date: December 31, 2026
• Est. primary completion date: February 2, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Life expectancy at least 12 weeks

• Histologically-confirmed MCL, with documentation of either overexpression of cyclin D1 or the presence of t(11:14)

• Relapsed (disease progression after the last treatment regimen) or refractory (failure to achieve a partial or complete response from the last treatment regimen) disease

• At least 1 line of prior systemic therapy including a BTK inhibitor and additional systemic therapy option

• Confirmed availability of tumor tissue, unless deemed unsafe per investigator assessment

• At least one bi-dimensionally measurable (defined as at least 1.5 cm) nodal lesion, or one bi-dimensionally measurable (at least 1 cm) extranodal lesion, as measured on CT scan

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

• Negative HIV test at screening

• Adequate hematological function

Exclusion Criteria:

• Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 3 months after the final dose of tocilizumab, 2 months after the final dose of glofitamab, whichever is longer

• Leukemic, non-nodal MCL

• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products

• Contraindication to obinutuzumab or rituximab, and either bendamustine or lenalidomide

• Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3

• Prior treatment with CAR-T cell therapy

• Treatment with systemic therapy or BTK inhibitors, or any investigational agent for the purposes of treating cancer within 2 weeks or 5 half-lives (whichever is shorter) prior to first study treatment

• Primary or secondary CNS lymphoma at the time of recruitment or history of CNS lymphoma

• Current or history of CNS disease, such as stroke, epilepisy, CNS vasculitis, or neurodegenerative disease

• History of other malignancy that could affect compliance with the protocol or interpretation of results

• Significant or extensive cardiovascular disease

• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at study enrollment or any major episode of infection within 4 weeks prior to the first study treatment

• Suspected or latent tuberculosis

• Positive test for hepatitis B virus (HBV) or hepatitis C virus (HCV)

• Known or suspected chronic active Epstein-Barr viral infection (EBV)

• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)

• Known history of progressive multifocal leukoencephalopathy (PML)

• Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better

• Administration of a live, attenuated vaccine within 4 weeks before first study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study

• Prior solid organ transplantation or allogenic stem cell transplant

• Eligibility for stem cell transplantation (SCT)

• Active autoimmune disease requiring treatment

• Prior treatment with systemic immunosuppressive medications within 2 weeks or five half-lives (whichever is shorter) prior to the first dose of study treatment

• Corticosteroid therapy within 2 weeks prior to first dose of study treatment

• Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis

• Clinically significant history of cirrhotic liver disease

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell

Intervention

Drug:
• Obinutuzumab
Participants will receive two 1000 mg pretreatments of intravenous (IV) obinutuzumab from Cycle 1 Day 1
• Glofitamab
Participants will receive IV glofitamab beginning Cycle 1 Day 8 for 12 cycles (cycle length = 21 days).
• Rituximab
Participants will receive IV rituximab every 28 days for up to 6 cycles (when in combination with bendamustine), or until disease progression (when in combination with lenalidomide).
• Bendamustine
Participants will receive IV bendamustine on Days 1 and 2 Q4W for 6 cycles (cycle length = 28 days).
• Lenalidomide
Participants will receive oral lenalidomide once daily on Days 1-21 Q4W until disease progression.
• Tocilizumab
Participants will receive IV tocilizumab as required to manage cytokine release syndrome (CRS) events.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital; Haematology Clinical Trials	Adelaide	South Australia
Australia	Epworth Hospital	Richmond	Victoria
Australia	Calvary Mater Newcastle; Medical Oncology	Waratah	New South Wales
Brazil	ICTR Curitiba	Curitiba	PR
Brazil	Hospital Mae de Deus	Porto Alegre	RS
Brazil	Americas Medical City	Rio de Janeiro	RJ
Brazil	Hospital A. C. Camargo; Oncologia	Sao Paulo	SP
Brazil	Hospital Alemao Oswaldo Cruz	Sao Paulo	SP
Brazil	Hospital Paulistano	Sao Paulo	SP
Brazil	Instituto D'Or Pesquisa e Ensino	Sao Paulo	SP
Brazil	Beneficencia Portuguesa de Sao Paulo	São Paulo	SP
Canada	Victoria Hospital - London Health Sciences Centre	London	Ontario
Canada	The Ottawa Hospital - General Campus	Ottawa	Ontario
China	Beijing Tong Ren Hospital, Capital Medical University	Beijing
China	The First Hospital of Jilin University	Changchun City
China	West China Hospital of Sichuan University	Chengdu City
China	Chongqing Cancer Hospital	Chongqing
China	Fujian Provincial Cancer Hospital	Fuzhou City
China	Sun yat-sen University Cancer Center; Internal Medicine of Oncology	Guangzhou
China	Guangxi Cancer Hospital of Guangxi Medical University	Nanning City
China	Fudan University Shanghai Cancer Center; Medical Oncology	Shanghai City
China	The First Affiliated Hospital of China Medical University	Shenyang City
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou City
China	The First Affiliated Hospital of Zhengzhou University; Branch Hospital in NEW ZHENGDONG District	Zhengzhou
China	Henan Cancer Hospital; Hematology department	Zhengzhou City
France	Hopital Claude Huriez; Hematologie	Lille
France	Hopital Saint Eloi; Hematologie Oncologie Medicale	Montpellier
France	CHU NANTES - Hôtel Dieu; Service d'Hematologie Clinique	Nantes
France	INSTITUT CURIE_SITE PARIS - Service d'Oncologie Médicale.	St Cloud
Italy	SC Ematologia, AO SS. Antonio e Biagio e C. Arrigo	Alessandria	Piemonte
Italy	Humanitas Gavazzeni;U.O. Oncologia Medica	Bergamo	Lombardia
Italy	Irccs Istituto Europeo Di Oncologia (IEO); Emato-Oncologia	Milano	Lombardia
Italy	A.O. Città della Salute e della Scienza D - Osp. S. Giov. Battista Molinette; Ematologia I	Torino	Piemonte
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron; Servicio de Hematologia	Barcelona
Spain	Hospital Universitario Puerta del Mar; Servicio de Hematologia	Cádiz	Cadiz
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Hematologia	La Coruna	LA Coruña
Spain	Hospital General Universitario J.M Morales Meseguer; Servicio de Hematología	Murcia
Sweden	Skånes University Hospital, Skånes Department of Onclology	Lund
Sweden	Akademiska sjukhuset, Onkologkliniken	Uppsala
Taiwan	National Taiwan Universtiy Hospital; Division of Hematology	Taipei
Taiwan	Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology	Taoyuan
United Kingdom	Oxford Churchill Hospital; Cancer and Haematology Centre,Level 2	Oxford
United Kingdom	Derriford Hospital; Haematology	Plymouth
United States	St. Luke's Hospital	Chesterfield	Missouri
United States	City of Hope Cancer Center	Duarte	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,  Australia,  Brazil,  Canada,  China,  France,  Italy,  Korea, Republic of,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)		From randomization to the first occurrence of disease progression or death from any cause (up to approximately 24 months)
Secondary	Complete response (CR) rate		Up to approximately 24 months
Secondary	Objective response rate (ORR)		Up to approximately 24 months
Secondary	Overall survival (OS)		From randomization to death from any cause (up to approximately 24 months)
Secondary	Time to deterioration in physical functioning/fatigue		From randomization to a 10-point decrease in physical functioning/10-point increase in fatigue compared to baseline (up to approximately 24 months)
Secondary	Investigator-assessed PFS		From randomization to disease progression or death from any cause (up to approximately 24 months)
Secondary	Investigator-assessed CR rate		Up to approximately 24 months
Secondary	Investigator-assessed ORR		Up to approximately 24 months
Secondary	Duration of Complete Response (DOCR)		From the initial occurrence of a documented CR until documented disease progression or death due to any cause, whichever occurs first (up to approximately 24 months)
Secondary	Duration of Response (DOR)		From the initial occurrence of a documented CR until documented disease progression or death due to any cause, whichever occurs first (up to approximately 24 months)
Secondary	Proportion of participants reporting each response option for item GP5 from the Functional Assessment of Cancer Therapy - General (FACT-G) subscale		Up to approximately 24 months
Secondary	Time to deterioration in lymphoma symptoms		From randomization to the first documentation of a 3-point or more decrease in score as assessed by the FACT-Lym lymphoma subscale (LymS) questionnaire (up to approximately 24 months)
Secondary	Proportion of participants experiencing a clinically meaningful improvement (3-point or more increase) in lymphoma symptoms as assessed through use of the FACT-Lym LymS		Up to approximately 24 months
Secondary	Change from baseline in physical functioning and fatigue at each cycle as assessed by the European Organization for Research and Treatment (EORTC) core Quality of Life Questionnaire (QLQ-C30)	The EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, and pain), global health status and quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The functioning and symptoms items are scored on a 4-point scale that ranges from "not at all" to "very much," and the global health status and QoL items are scored on a 7-point scale that ranges from "very poor" to "excellent."	Up to approximately 24 months
Secondary	Change from baseline in lymphoma symptoms at each cycle as assessed by the FACT-Lym LymS		Up to approximately 24 months
Secondary	Serum concentration of glofitamab		Up to approximately 24 months
Secondary	Incidence of anti-drug antibodies (ADAs)		Up to approximately 24 months