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

NCT04313608 | Completed Phase 1 Results FDA Drug

• 1 other identifier: GO41943
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 3

Brief Summary

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).

Conditions

B-cell Lymphoma

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• 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

  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

  Up to approximately 16 months

• Maximum Serum Concentration (Cmax) of Glofitamab

  Cycle 1 Day 8 and Cycle 2 Day 1

Study Arms (2)

Arm A: Glofit-GemOx

EXPERIMENTAL

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: Glofitamab; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Obinutuzumab; Drug: Tocilizumab

Arm B: Mosun-GemOx

EXPERIMENTAL

Participants will receive up to 8 cycles of Mosun-GemOx (mosunetuzumab in combination with gemcitabine and oxaliplatin) administered in 21-day cycles.

Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Mosunetuzumab; Drug: Tocilizumab

Interventions

Glofitamab DRUG

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.

Also known as: RO7082859

Arm A: Glofit-GemOx

Gemcitabine DRUG

Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.

Arm A: Glofit-GemOx; Arm B: Mosun-GemOx

Oxaliplatin DRUG

Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.

Arm A: Glofit-GemOx; Arm B: Mosun-GemOx

Mosunetuzumab DRUG

Participants will receive IV mosunetuzumab in combination with gemcitabine and oxaliplatin for up to 8 cycles.

Also known as: RO7030816

Arm B: Mosun-GemOx

Obinutuzumab DRUG

Participants will receive a single dose of IV obinutuzumab 7 days prior to the first administration of glofitamab.

Also known as: RO5072759

Arm A: Glofit-GemOx

Tocilizumab DRUG

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

Also known as: RO4877533

Arm A: Glofit-GemOx; Arm B: Mosun-GemOx

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (3)

Prince of Wales Hospital; Haematology

Randwick, New South Wales, 2031, Australia

Location

Monash Health Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

glofitamab; Gemcitabine; Oxaliplatin; obinutuzumab; tocilizumab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

1-800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2020
• First Posted: March 18, 2020
• Study Start: June 4, 2020
• Primary Completion: October 26, 2021
• Study Completion: October 26, 2021
• Last Updated: March 25, 2024
• Results First Posted: March 25, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share

Locations

AU (3)