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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

Description:

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).

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • High Grade B-Cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating the Safety and Efficacy of RO7082859 or Mosunetuzumab (RO7030816) in Combination With Gemcitabine Plus Oxaliplatin in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma and High-Grade Large B-Cell Lymphoma
  • Official Title: A Phase Ib, Open-Label, Multicenter Study Evaluating the Safety and Efficacy of RO7082859 or Mosunetuzumab (RO7030816) in Combination With Gemcitabine Plus Oxaliplatin in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma and High-Grade Large B-Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: GO41943
  • NCT ID: NCT04313608

Conditions

  • B-cell Lymphoma

Interventions

DrugSynonymsArms
RO7082859Arm A: CD20-TCB-GemOx
GemcitabineArm A: CD20-TCB-GemOx
OxaliplatinArm A: CD20-TCB-GemOx
MosunetuzumabRO7030816Arm B: Mosun-GemOx
ObinutuzumabArm A: CD20-TCB-GemOx

Purpose

This study is designed to evaluate the safety and efficacy of a CD20-CD3-bispecific antibody in combination with gemcitabine and oxaliplatin in participants with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBCL).

Trial Arms

NameTypeDescriptionInterventions
Arm A: CD20-TCB-GemOxExperimentalParticipants will receive 6 cycles of CD20-TCB-GemOx (RO7082859 in combination with gemcitabine and oxaliplatin) administered in 21-day cycles.
  • RO7082859
  • Gemcitabine
  • Oxaliplatin
  • Obinutuzumab
Arm B: Mosun-GemOxExperimentalParticipants will receive 6 cycles of Mosun-GemOx (mosunetuzumab in combination with gemcitabine and oxaliplatin) administered in 21-day cycles.
  • Gemcitabine
  • Oxaliplatin
  • Mosunetuzumab

Eligibility Criteria

        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, 4 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 RO7082859. 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 RO7082859, 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

          -  In first relapse of B-cell lymphoma and 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
             RO7082859 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

          -  Active autoimmune disease requiring treatment

          -  Prior systemic immunosuppressive medications (including, but not limited to,
             cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents) with
             the exception of corticosteroid treatment consisting of </=10 mg/day prednisone or
             equivalent within 2 weeks prior to the first dose of study treatment

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

          -  Clinically significant history of liver disease, including viral or other hepatitis,
             current alcohol abuse, or cirrhosis
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Adverse Events (AEs)
Time Frame:Up to 12 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Tolerability of Study Treatment as Measured by Dose Interruptions, Dose Reductions, Dose Intensity, and Treatment Discontinuation due to AEs
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure:Complete Response (CR) Based on PET/CT as Determined by the Investigator According to the 2014 Lugano Response Criteria
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure: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
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure:Minimum Serum Concentration (Cmin) of the CD20-CD3-Bispecific Antibody
Time Frame:At pre-defined intervals from baseline up to 12 months
Safety Issue:
Description:
Measure:Maximum Serum Concentration (Cmax) of the CD20-CD3-Bispecific Antibody
Time Frame:At pre-defined intervals from baseline up to 12 months
Safety Issue:
Description:
Measure:Area Under the Concentration-Time Curve (AUC) of the CD20-CD3-Bispecific Antibody
Time Frame:At pre-defined intervals from baseline up to 12 months
Safety Issue:
Description:
Measure:Proportion of Participants with Anti-Drug Antibodies (ADAs) to the CD20-CD3-Bispecific Antibody
Time Frame:Baseline up to 12 months
Safety Issue:
Description:
Measure:Proportion of Participants with ADAs to Mosunetuzumab
Time Frame:Baseline up to 12 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

March 17, 2020