Diffuse Large B-cell Lymphoma
Conditions
Brief summary
This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab following first-line diffuse large B-cell lymphoma (DLBCL) immunochemotherapy in participants with a best response of stable disease or partial response, or in elderly/unfit participants with previously untreated DLBCL, or subcutaneous mosunetuzumab in combination with polatuzumab vedotin IV in elderly/unfit participants with previously untreated DLBCL.
Interventions
DRUGMosunetuzumab Intravenous (IV)
Participants in cohorts A and B will receive IV mosunetuzumab.
DRUGMosunetuzumab Subcutaneous (SC)
Participants in Cohort C will receive SC mosunetuzumab.
DRUGPolatuzumab Vedotin
Participants in Cohort C will receive IV polatuzumab vedotin.
DRUGTocilizumab
Participants will receive tocilizumab via IV as needed to manage severe cytokine release syndrome (CRS).
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for All Cohorts * At least one bi-dimensionally measurable nodal lesion, defined as \> 1.5 cm in its longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as \> 1.0 cm in its longest diameter * Adequate hematologic function * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2; with the exception of South Korea, where participants 80 years or older with ECOG \>/= 2 will not be eligible Inclusion Criteria Specific to Cohort A Participants in Cohort A must also meet the following criteria for study entry: * Histologically confirmed DLBCL according to World Health Organization (WHO) 2016 expected to express the cluster of differentiation-20 (CD20) antigen * One prior therapy with any systemic anthracycline-based chemoimmunotherapy containing regimen for previously untreated DLBCL * Best response of SD or PR to prior systemic chemoimmunotherapy at the end of induction treatment in accordance with the Lugano 2014 criteria Inclusion Criteria Specific to Cohorts B and C Participants in Cohorts B and C must also meet the following criteria for study entry: * Previously untreated, histologically confirmed, DLBCL according to WHO 2016 classification * Age \>/= 80 years, or * Age 65-79 years and considered ineligible for chemoimmuotherapy (R-CHOP) with at least one of the following: Impairment in at least two activity of daily living (ADL) components as defined in the protocol; impairment in at least two instrumental ADL components as defined in the protocol; cumulative illness rating scale - geriactic (CIRS-G) score of at least one cormorbidity with a severity score of 3-4 (not including lymphoma and hematologic deficiencies due to lymphoma) or a score of 2 in \>/= 8 comorbidities; impairment in cardiac function, renal function, liver function, or other comorbidities such that the participant is unfit for full-dose immunochemotherapy, such as rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) * Participants with an initial ECOG performance status of 3 may be considered during screening if the performance status is DLBCL-related and if pre-phase treatment during the screening phase (not more than 100 mg/day up to 7 days prior to Cycle 1 Day 1) results in an improvement of ECOG performance status to \</= 2 prior to enrollment
Exclusion criteria
for All Cohorts Participants who meet any of the following criteria will be excluded from study entry: * Transformed lymphoma * CNS lymphoma * Prior treatment with mosunetuzumab * Prior stem cell transplant (autologous and allogeneic) * History of confirmed progressive multifocal leukoencephalopathy (PML) * Known or suspected chronic active Epstein Barr virus (CAEBV), hepatitis B, hepatitis C (HCV), or Human Immunodeficiency Virus (HIV) * Known or suspected history of hemophagocytic lymphohistiocytosis (HLH) * Positive SARS-CoV-2 antigen or PCR test within 30 days prior to Cycle 1 Day 1 * Prior solid organ transplantation * Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease * Clinically significant history of liver disease * Prior treatment with radiotherapy within 2 weeks prior to Cycle 1, Day 1 (C1D1) * Significant cardiovascular disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants with Adverse Events | Baseline through approximately 90 days after last study treatment |
| Positron Emission Tomography-Computed Tomography (PET-CT) Complete Response (CR) Rate at Time of Primary Response Assessment (PRA) According to Lugano 2014 Response Criteria (Cohort A) | 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days) |
| PET-CT Objective Response Rate (ORR) at PRA According to Lugano 2014 Response Criteria as Determined by the Investigator (Cohort B) | 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days) |
| PET-CT ORR at PRA According to the Lugano 2014 Criteria as Determined by an Independent Review Committee (IRC) (Cohort C) | 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days) |
Secondary
| Measure | Time frame |
|---|---|
| Volume of Distribution at Steady State (Vss) of Mosunetuzumab IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| Maximum Serum Concentration (Cmax) of Mosunetuzumab SC | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| Time to Maximum Serum Concentration (Tmax) of Mosunetuzumab SC | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| Minimum Serum Concentration (Cmin) of Mosunetuzumab SC | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| Area Under the Curve (AUC) of Mosunetuzumab SC | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| Clearance (CL) of Mosunetuzumab SC | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| Volume of Distribution at Steady State (Vss) of Mosunetuzumab SC | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| Maximum Serum Concentration (Cmax) of Polatuzumab Vedotin IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| Minimum Serum Concentration (Cmin) of Polatuzumab Vedotin IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| Area Under the Curve (AUC) of Polatuzumab Vedotin IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| Clearance (CL) of Polatuzumab Vedotin IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| Volume of Distribution at Steady State (Vss) of Polatuzumab Vedotin IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| End of Infusion Concentration (Ceoi) of Polatuzumab Vedotin IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| Trough Concentration (Ctrough) of Polatuzumab Vedotin IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| Maximum Serum Concentration (Cmax) of Mosunetuzumab IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| Objective Response Rate (ORR), Defined as the Proportion of Participants with a Complete Response (CR) or Partial Response (PR) at PRA as Determined by the Investigator (Cohorts A and C) | Baseline through 2 years after PRA (up to a total of approximately 2.5 years) |
| Best ORR (CR or PR at any time) During the Study Based on PET-CT and/or CT Scans as Determined by the Investigator (All Cohorts) and by IRC (Cohort C) | Baseline through 2 years after PRA (up to a total of approximately 2.5 years) |
| Duration of Response (DOR) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C) | From the first occurrence of a documented objective response to disease progression, relapse, or death, whichever occurs first (up to approximately 2.5 years) |
| Duration of Confirmed Response (DOCR) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C) | From the first occurrence of a documented CR to disease progression or relapse, or death from any cause, whichever occurs first (up to approximately 2.5 years) |
| Progression-Free Survival (PFS) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C) | From the first study treatment to the first occurrence of disease progression, relapse, or death, whichever occurs first (up to approximately 2.5 years) |
| Overall Survival (OS) | From the first study treatment to death from any cause |
| Time to Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Physical Functioning and Fatigue (Cohorts B and C) | From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years) |
| Time to Deterioration in European Organization for Research and Treatment of Cancer Item Library (EORTC-IL17) Physical Functioning (Cohorts B and C) | From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years) |
| Time to Deterioration in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale (Cohorts B and C) | From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years) |
| Proportion of Participants Achieving a Clinically Meaningful Improvement in Physical Functioning as Measured by EORTC QLQ-C30 (Cohorts B and C) | From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years) |
| Proportion of Participants Achieving a Clinically Meaningful Improvement in Physical Functioning as Measured by EORTC IL17 (Cohorts B and C) | From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years) |
| Anti-Drug Antibodies (ADAs) to Mosunetuzumab | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin (Cohort C) | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| PET-CT Rate According to the Lugano 2014 Criteria at PRA as Determined by the Investigator (Cohorts B and C) and IRC (Cohort C) | 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days) |
| Minimum Serum Concentration (Cmin) of Mosunetuzumab IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| Area Under the Curve (AUC) of Mosunetuzumab IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
| Clearance (CL) of Mosunetuzumab IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
Countries
Israel, Poland, South Korea, Spain, Taiwan, United States
Outcome results
None listed