A Study Evaluating the Safety and Efficacy of Glofitamab or Mosunetuzumab in Combination With Gemcitabine Plus Oxaliplatin in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma and High-Grade Large B-Cell Lymphoma

A Phase Ib, Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Glofitamab or Mosunetuzumab in Combination With Gemcitabine Plus Oxaliplatin in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma and High-Grade Large B-Cell Lymphoma

This study is designed to evaluate the safety and efficacy of glofitamab or mosunetuzumab in combination with gemcitabine and oxaliplatin (Glofit-GemOx or Mosun-GemOx) in participants with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBCL).

Study Overview

• Status: Completed
• Conditions: B-cell Lymphoma
• Intervention / Treatment: Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Tocilizumab; Drug: Glofitamab; Drug: Obinutuzumab; Drug: Mosunetuzumab

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital; Haematology
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health Monash Medical Centre
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0,1, or 2
• Histologically confirmed B-cell lymphoma, including one of the following diagnoses per the 2016 World Health Organization (WHO) classification of lymphoid neoplasms: DLBCL, not otherwise specified (NOS); HGBCL with MYC and BCL2 and/or BCL6 rearrangements; HGBCL, NOS
• R/R disease, defined as follows: Relapse: disease that has recurred following a response that lasted >/=6 months after completion of last line of therapy; Refractory: disease that progressed during therapy or progressed within 6 months (<6 months) of prior therapy
• At least one line of prior systemic therapy
• At least one bi-dimensionally measurable nodal lesion or one bi-dimensionally measurable extranodal lesion, as measured on positron emission tomography-computed tomography (PET/CT) scan
• Adequate hematologic function
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as follows: Women must remain abstinent or use contraceptive methods with a failure rate of <1% per year during the treatment period and for at least 18 months after the final dose of obinutuzumab, 6 months after the final dose of gemcitabine, 9 months after the final dose of oxaliplatin, 3 months after the final dose of mosunetuzumab, 3 months after the final dose of tocilizumab, and 2 months after the final dose of glofitamab. Women must refrain from donating eggs during this same period
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm, as follows: With a female partner of childbearing potential or pregnant female partners, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for at least 2 months after the final dose of glofitamab, 2 months after the final dose of mosunetuzumab, 2 months after the final dose of tocilizumab (if applicable), 3 months after the final dose of obinutuzumab, and 6 months after the final dose of oxaliplatin or gemcitabine to avoid exposing the embryo. Men must refrain from donating sperm during this same period.

Exclusion Criteria

• Participant has failed only one prior line of therapy and is a candidate for stem cell transplantation
• 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, gemcitabine, oxaliplatin, or tocilizumab
• Prior treatment with a bispecific antibody targeting both CD20 and CD3, including glofitamab and mosunetuzumab
• Grade >1 peripheral neuropathy
• Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to first study treatment
• Treatment with monoclonal antibodies for the purposes of treating cancer within 4 weeks prior to the first study treatment
• Primary or secondary central nervous system (CNS) lymphoma at the time of recruitment or history of CNS lymphoma
• Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• History of other malignancy that could affect compliance with the protocol or interpretation of results
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including 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) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection (as evaluated by the investigator) within 4 weeks prior to first study treatment
• Suspected or latent tuberculosis
• Positive test results for chronic hepatitis B virus (HBV) infection
• Positive test results for hepatitis C virus (HCV) antibody
• Known HIV-seropositive status
• Known or suspected chronic active Epstein-Barr virus infection
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• History of progressive multifocal leukoencephalopathy
• Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better (with the exception of alopecia and anorexia)
• Administration of a live, attenuated vaccine within 4 weeks prior to the first study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study
• Prior solid organ transplantation
• Prior allogenic stem cell transplant
• Active autoimmune disease requiring treatment
• Prior treatment with systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 4 weeks prior to the first dose of study treatment
• Corticosteroid therapy within 2 weeks prior to first dose of study treatment, with exceptions defined by the study protocol
• Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis
• Clinically significant history of liver disease, including cirrhosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Glofit-GemOx; Participants will receive up to 8 cycles of Glofit-GemOx (glofitamab in combination with gemcitabine and oxaliplatin) administered in 21-day cycles, followed by up to 4 cycles of glofitamab monotherapy. A single dose of obinutuzumab will be administered 7 days prior to the first dose of glofitamab.	Drug: Gemcitabine; Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.; Drug: Oxaliplatin; Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.; Drug: Tocilizumab; Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).; Other Names: RO4877533; Drug: Glofitamab; Participants will receive intravenous (IV) glofitamab in combination with gemcitabine and oxaliplatin for up to 8 cycles, followed by up to 4 cycles of glofitamab monotherapy.; Other Names: RO7082859; Drug: Obinutuzumab; Participants will receive a single dose of IV obinutuzumab 7 days prior to the first administration of glofitamab.; Other Names: RO5072759
Experimental: Arm B: Mosun-GemOx; Participants will receive up to 8 cycles of Mosun-GemOx (mosunetuzumab in combination with gemcitabine and oxaliplatin) administered in 21-day cycles.	Drug: Gemcitabine; Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.; Drug: Oxaliplatin; Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.; Drug: Tocilizumab; Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).; Other Names: RO4877533; Drug: Mosunetuzumab; Participants will receive IV mosunetuzumab in combination with gemcitabine and oxaliplatin for up to 8 cycles.; Other Names: RO7030816

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Deaths Due to Adverse Events (AEs)	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events.	Baseline - 90 days after last dose of study treatment
Number of Treatment Discontinuations Due to AE	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events.	Baseline - 90 days after last dose of study treatment
Proportion of Participants With Serious Adverse Events (SAEs)	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events.	Baseline - 90 days after last dose of study treatment
Proportion of Participants With Cytokine Release Syndrome (CRS) by Grade of Severity	Severity of CRS was determined according to the American Society for Transplantation and Cell Therapy (ASTCT) Consensus Grading Criteria, in which Grade 1 as fever (≥38.0°C) with or without other symptoms; Grade 2 as fever with hypotension not requiring vasopressors and/or hypoxia requiring the use of oxygen (low-flow); and Grade 3 as fever with hypotension requiring one vasopressor with or without vasopressin and/or hypoxia requiring the use of oxygen (high-flow).	Baseline - 90 days after last dose of study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability of Study Treatment as Measured by Dose Interruptions, Dose Reductions, and Treatment Discontinuation Due to AEs		Up to approximately 16 months
Complete Response (CR) Based on PET/CT as Determined by the Investigator According to the 2014 Lugano Response Criteria	Per the 2014 Lugano Response Criteria for malignant lymphoma a CR = complete metabolic response with a score of 1, 2, or 3 on a 5-point scale (5PS), with higher scores indicating more extensive disease.	Up to approximately 16 months
Objective Response Rate (ORR), Defined as the Proportion of Participants With a Best Overall Response of Partial Response (PR) or CR, as Determined by the Investigator According to the 2014 Lugano Response Criteria	Per the 2014 Lugano Response Criteria for malignant lymphoma a CR = complete metabolic response with a score of 1, 2, or 3 on a 5-point scale (5PS), while a PR = partial metabolic response with a score of 4 or 5 on 5PS with higher scores indicating more extensive disease.	Up to approximately 16 months
Maximum Serum Concentration (Cmax) of Glofitamab		Cycle 1 Day 8 and Cycle 2 Day 1

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2020
• Primary Completion (Actual): October 26, 2021
• Study Completion (Actual): October 26, 2021

Study Registration Dates

• First Submitted: March 17, 2020
• First Submitted That Met QC Criteria: March 17, 2020
• First Posted (Actual): March 18, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Oxaliplatin; Obinutuzumab; Gemcitabine
• Other Study ID Numbers: GO41943

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No