B-cell Non-Hodgkin Lymphoma
Conditions
Brief summary
This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (M-CHOP) and, subsequently, in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) plus polatuzumab vedotin (CHP-pola) in participants with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL), and in previously untreated participants with diffuse large B-cell lymphoma (DLBCL).
Interventions
DRUGTocilizumab
Participants will receive tocilizumab via IV.
DRUGMosunetuzumab
Participants will receive intravenous (IV) mosunetuzumab.
DRUGPolatuzumab Vedotin
Participants will receive polatuzumab vedotin via IV.
DRUGRituxumab
Participants will receive rituxumab via IV.
DRUGCyclophosphamide
Participants will receive cyclophosphamide via IV.
DRUGDoxorubicin
Participants will receive doxorubicin via IV.
DRUGVincristine
Participants will receive vincristine via IV.
DRUGPrednisone
Participants will receive oral prednisone.
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 Phase Ib and Phase II Portions * 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 * Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2 * Adequate hematologic function Inclusion Criteria for Phase Ib Portion Participants must also meet the following criteria for study entry into the Phase Ib portion: * Histologically confirmed B-cell NHL according to the World Health Organization (WHO) 2016 classification expected to express the cluster of differentiation-20 (CD20) antigen * Relapsed or refractory (R/R) B-cell NHL after at least one prior systemic lymphoma therapy * Treatment with at least one prior CD20-directed therapy * Group B only: no prior treatment with polatuzumab vedotin Inclusion Criteria for Phase II Portion Participants must also meet the following criteria for study entry in the Phase II portion: * Previously untreated, histologically confirmed DLBCL according to WHO 2016 classification * International Prognostic Index (IPI) score of 2-5
Exclusion criteria
* Prior treatment with mosunetuzumab * Prior allogenic stem-cell transplant * Current Grade \>1 peripheral neuropathy * Participants with 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) * Prior solid organ transplantation * History of autoimmune disease * Current or past history of central nervous system (CNS) lymphoma * Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease * Significant cardiovascular disease or pulmonary disease * Clinically significant history of liver disease * Recent major surgery within 4 weeks before the start of C1D1, other than superficial lymph node biopsies for diagnosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) Rate at the Time of Primary Response Assessment (PRA) Based on Positron Emission Tomography - Computed Tomography (PET-CT) as Determined by Independent Review Committee (IRC) | 6-8 weeks after either C6D1 or last dose of study treatment | The CR rate was defined as the percentage of participants with CR. Assessments were made according to the Lugano 2014 Response Criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) at PRA Based on PET-CT as Determined by the Investigator (Phase II) | 6-8 weeks after C6D1 or last dose of study treatment | ORR is defined as a CR or PR at the time of primary assessment based on PET-CT, as determined by the investigator. |
| ORR at PRA Based on CT Only as Determined by the Investigator (Phase II) | 6-8 weeks after C6D1 or last dose of study treatment | ORR is defined as a CR or PR at the time of primary assessment based on CT only, as determined by the investigator. |
| Best ORR Based on PET-CT and/or CT Scan as Determined by the Investigator (Phase II) | Up to approximately 50 months | Best ORR was defined as CR or PR at any time on study and based on PET-CT or CT only as determined by the investigator. |
| Duration of Response (DOR) as Determined by the Investigator (Phase II) | Up to approximately 50 months | DOR is defined as the time from the first occurrence of a documented objective response to disease progression or relapse as determined by the investigator, or death from any cause, whichever occurs first. The range values (min-max) are based on censored observations (if a participant did not experience disease progression or death prior to the end of the trial DOR was censored on the date of the last tumor assessment). |
| Progression-free Survival (PFS) as Determined by the Investigator (Phase II) | Up to approximately 50 months | PFS is defined as the time from randomization to the first occurrence of disease progression or relapse as determined by the investigator, or death from any cause, whichever occurs first. The earliest contributing event to PFS is reported. The range (min-max) values are based on censored observations (participants without a baseline-evaluable tumor assessment were censored at the date of randomization or first study treatment, plus 1 day). |
| PFS at 1 Year as Determined by the Investigator (Phase II) | 1 year | PFS at 1 year is defined as the proportion of participants with disease progression or relapse as determined by the investigator, or death from any cause within 1 year of randomization. |
| Event-free Survival (EFS) as Determined by the Investigator (Phase II) | Up to 50 months | EFS is defined as the time from randomization to the first occurrence of disease progression or relapse, as determined by the investigator, initiation of new anti-lymphoma therapy (NALT), or death from any cause, whichever occurs first. The range values (min-max) are based on censored observations (if a participant did not experience disease progression or death prior to the end of the trial DOR was censored on the date of the last tumor assessment). |
| CR Rate at PRA Based on CT Only as Determined by the Investigator (Phase II) | 6-8 weeks after C6D1 or last dose of study treatment | — |
| Time to Deterioration in Physical Functioning and Fatigue as Measured by the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTC QLQ-C30) | C1D1 through follow-up period (to begin 2 years after PRA or at the time of study drug discontinuation) | — |
| Polatuzumab Vedotin Serum Concentrations | C2D1, C6D1 | — |
| Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C1D1-C6D1 | — |
| Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C1D1-C6D1 | — |
| Mosunetuzumab Serum Concentrations | C1D1-C5D1 | — |
| Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Cycles 1, 2, 6, 16, and at early discontinuation visit or at PRA (6-8 weeks after either C6D1 or last dose of study treatment) | Participants are considered to have treatment-induced ADA responses if they are ADA negative or missing data at baseline and then develop an ADA response following study drug administration. Participants are considered to have treatment-enhanced ADA responses if they are ADA positive at baseline and the titer of one or more post baseline samples is at least 4-fold greater than the titer of the baseline sample. Patients are considered to be negative for ADAs if they are ADA negative at all timepoints or if they are ADA positive at baseline but do not have any post-baseline samples with a titer that is at least 4-fold greater than the titer of the baseline sample (treatment unaffected). |
| Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Cycles 1, 2, 6, and at early discontinuation visit or at PRA (6-8 weeks after either C6D1 or last dose of study treatment) | Participants are considered to have treatment-induced ADA responses if they are ADA negative or missing data at baseline and then develop an ADA response following study drug administration. Participants are considered to have treatment-enhanced ADA responses if they are ADA positive at baseline and the titer of one or more post baseline samples is at least 4-fold greater than the titer of the baseline sample. Patients are considered to be negative for ADAs if they are ADA negative at all timepoints or if they are ADA positive at baseline but do not have any post-baseline samples with a titer that is at least 4-fold greater than the titer of the baseline sample (treatment unaffected). |
| Time to Deterioration in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale | C1D1 through follow-up period (to begin 2 years after PRA or at the time of study drug discontinuation) | — |
Countries
Austria, France, Poland, South Korea, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A1: Phase Ib Mosunetuzumab + CHOP Participants with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) received mosunetuzumab on Cycle 1 Day 1 (C1D1), C1D8, and C1D15, then on Day 1 of subsequent cycles. In addition, participants received cyclophosphamide, doxorubicin, and vincristine on D1, and prednisone on D1-D5 (CHOP). Treatment was given for 6 cycles (cycle length = 21 days). | 3 |
| Group A2: Phase Ib Mosunetuzumab + CHOP Participants with relapsed/refractory (R/R) B-cell NHL received mosunetuzumab on Cycle 1 Day 1 (C1D1), C1D8, and C1D15, then on Day 1 of subsequent cycles. In addition, participants received cyclophosphamide, doxorubicin, and vincristine on D1, and prednisone on D1-D5. Treatment was given for 6 cycles (cycle length = 21 days). | 4 |
| Group B: Phase Ib Mosunetuzumab + CHP-Pola Participants with R/R NHL received 6 cycles of mosunetuzumab (M) + cyclophosphamide, doxorubicin, prednisone (CHP), and polatuzumab vedotin (Pola) (cycle length = 21 days). Participants received M on C1D2, C1D8, C1D15, C2D2, and on D1 of subsequent cycles if well tolerated. CHP-pola was given on D1 of each cycle (D1-D5 for prednisone). | 8 |
| Group C: Phase II Mosunetuzumab + CHOP Participants with previously untreated diffuse large B-cell lymphoma (DLBCL) received mosunetuzumab on Cycle 1 Day 1 (C1D1), C1D8, and C1D15, then on Day 1 of subsequent cycles. In addition, participants received cyclophosphamide, doxorubicin, and vincristine on D1, and prednisone on D1-D5 (CHOP). Treatment was given for 6 cycles (cycle length = 21 days). | 40 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) Participants received M-CHP-Pola for 6 cycles (cycle length = 21 days). Participants received M on C1D1, C1D8, and C1D15, then on D1 of subsequent cycles. CHP-pola was given on D1 of each cycle (D1-D5 for prednisone). | 40 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) Participants received R-CHP-Pola for 6 cycles (cycle length = 21 days). R-CHP-pola was given on D1 of each cycle (D1-D5 for prednisone). | 22 |
| Total | 117 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 1 | 6 | 9 | 5 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 2 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Screen failure or enrolled in error | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Group A1: Phase Ib Mosunetuzumab + CHOP | Group A2: Phase Ib Mosunetuzumab + CHOP | Group B: Phase Ib Mosunetuzumab + CHP-Pola | Group C: Phase II Mosunetuzumab + CHOP | Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 72.0 Years STANDARD_DEVIATION 13 | 71.3 Years STANDARD_DEVIATION 3.4 | 60.1 Years STANDARD_DEVIATION 18 | 63.4 Years STANDARD_DEVIATION 11 | 65.0 Years STANDARD_DEVIATION 10 | 57.7 Years STANDARD_DEVIATION 14.3 | 63.2 Years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 5 Participants | 36 Participants | 35 Participants | 18 Participants | 100 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 10 Participants | 5 Participants | 0 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 4 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) White | 3 Participants | 4 Participants | 8 Participants | 28 Participants | 30 Participants | 20 Participants | 93 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 3 Participants | 18 Participants | 14 Participants | 8 Participants | 44 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 5 Participants | 22 Participants | 26 Participants | 14 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 1 / 4 | 6 / 8 | 9 / 40 | 5 / 40 | 3 / 22 |
| other Total, other adverse events | 3 / 3 | 4 / 4 | 8 / 8 | 40 / 40 | 38 / 38 | 22 / 22 |
| serious Total, serious adverse events | 3 / 3 | 4 / 4 | 6 / 8 | 20 / 40 | 24 / 38 | 3 / 22 |
Outcome results
Primary
Complete Response (CR) Rate at the Time of Primary Response Assessment (PRA) Based on Positron Emission Tomography - Computed Tomography (PET-CT) as Determined by Independent Review Committee (IRC)
The CR rate was defined as the percentage of participants with CR. Assessments were made according to the Lugano 2014 Response Criteria.
Time frame: 6-8 weeks after either C6D1 or last dose of study treatment
Population: The intent-to-treat (ITT) population consisted of all participants. Efficacy analyses for Arms A1, A2, and B were exploratory. The primary efficacy analysis compared Arm 1 vs Arm 2, with participants grouped according to the treatment arm assigned at randomization. Group C was included in secondary efficacy analysis, and efficacy analyses for Arms A1, A2, and B were exploratory.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Complete Response (CR) Rate at the Time of Primary Response Assessment (PRA) Based on Positron Emission Tomography - Computed Tomography (PET-CT) as Determined by Independent Review Committee (IRC) | 72.5 Percentage of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Complete Response (CR) Rate at the Time of Primary Response Assessment (PRA) Based on Positron Emission Tomography - Computed Tomography (PET-CT) as Determined by Independent Review Committee (IRC) | 77.3 Percentage of participants |
95% CI: [-30.61, 21.07]
Secondary
Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin
Participants are considered to have treatment-induced ADA responses if they are ADA negative or missing data at baseline and then develop an ADA response following study drug administration. Participants are considered to have treatment-enhanced ADA responses if they are ADA positive at baseline and the titer of one or more post baseline samples is at least 4-fold greater than the titer of the baseline sample. Patients are considered to be negative for ADAs if they are ADA negative at all timepoints or if they are ADA positive at baseline but do not have any post-baseline samples with a titer that is at least 4-fold greater than the titer of the baseline sample (treatment unaffected).
Time frame: Cycles 1, 2, 6, and at early discontinuation visit or at PRA (6-8 weeks after either C6D1 or last dose of study treatment)
Population: The immunogenicity analysis population included all participants with at least one ADA assessment. The number of participants analyzed are the values for baseline-evaluable participants and post-baseline evaluable participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Positive for treatment-enhanced ADA | 0 Number of participants |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Negative for treatment-emergent ADA | 6 Number of participants |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Positive sample at baseline | 0 Number of participants |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Not positive at baseline | 8 Number of participants |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Positive for treatment-emergent ADA | 0 Number of participants |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Positive for treatment-induced ADA | 0 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Positive for treatment-induced ADA | 0 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Positive for treatment-enhanced ADA | 0 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Not positive at baseline | 32 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Positive for treatment-emergent ADA | 0 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Negative for treatment-emergent ADA | 37 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Positive sample at baseline | 1 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Negative for treatment-emergent ADA | 20 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Positive sample at baseline | 2 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Positive for treatment-induced ADA | 1 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Not positive at baseline | 19 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Positive for treatment-enhanced ADA | 0 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin | Positive for treatment-emergent ADA | 1 Number of participants |
Secondary
Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab
Participants are considered to have treatment-induced ADA responses if they are ADA negative or missing data at baseline and then develop an ADA response following study drug administration. Participants are considered to have treatment-enhanced ADA responses if they are ADA positive at baseline and the titer of one or more post baseline samples is at least 4-fold greater than the titer of the baseline sample. Patients are considered to be negative for ADAs if they are ADA negative at all timepoints or if they are ADA positive at baseline but do not have any post-baseline samples with a titer that is at least 4-fold greater than the titer of the baseline sample (treatment unaffected).
Time frame: Cycles 1, 2, 6, 16, and at early discontinuation visit or at PRA (6-8 weeks after either C6D1 or last dose of study treatment)
Population: The immunogenicity analysis population included all participants with at least one ADA assessment. The number of participants analyzed are the values for baseline-evaluable participants and post-baseline evaluable participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive for treatment-emergent ADA | 0 Number of participants |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Negative for treatment-emergent ADA | 3 Number of participants |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive for treatment-induced ADA | 0 Number of participants |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive for treatment-enhanced ADA | 0 Number of participants |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Not positive at baseline | 3 Number of participants |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive sample at baseline | 0 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive for treatment-emergent ADA | 0 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Not positive at baseline | 4 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Negative for treatment-emergent ADA | 4 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive sample at baseline | 0 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive for treatment-enhanced ADA | 0 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive for treatment-induced ADA | 0 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive for treatment-enhanced ADA | 0 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Negative for treatment-emergent ADA | 6 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Not positive at baseline | 8 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive for treatment-emergent ADA | 0 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive for treatment-induced ADA | 0 Number of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive sample at baseline | 0 Number of participants |
| Group C: Phase II Mosunetuzumab + CHOP | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Negative for treatment-emergent ADA | 39 Number of participants |
| Group C: Phase II Mosunetuzumab + CHOP | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive for treatment-induced ADA | 0 Number of participants |
| Group C: Phase II Mosunetuzumab + CHOP | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive sample at baseline | 0 Number of participants |
| Group C: Phase II Mosunetuzumab + CHOP | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive for treatment-enhanced ADA | 0 Number of participants |
| Group C: Phase II Mosunetuzumab + CHOP | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive for treatment-emergent ADA | 0 Number of participants |
| Group C: Phase II Mosunetuzumab + CHOP | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Not positive at baseline | 38 Number of participants |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Negative for treatment-emergent ADA | 37 Number of participants |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive sample at baseline | 0 Number of participants |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Not positive at baseline | 33 Number of participants |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive for treatment-emergent ADA | 0 Number of participants |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive for treatment-induced ADA | 0 Number of participants |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab | Positive for treatment-enhanced ADA | 0 Number of participants |
Secondary
Best ORR Based on PET-CT and/or CT Scan as Determined by the Investigator (Phase II)
Best ORR was defined as CR or PR at any time on study and based on PET-CT or CT only as determined by the investigator.
Time frame: Up to approximately 50 months
Population: The intent-to-treat (ITT) population consisted of all participants. Efficacy analyses for Arms A1, A2, and B were exploratory.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Best ORR Based on PET-CT and/or CT Scan as Determined by the Investigator (Phase II) | 95.0 Percentage of responders |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Best ORR Based on PET-CT and/or CT Scan as Determined by the Investigator (Phase II) | 85.0 Percentage of responders |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Best ORR Based on PET-CT and/or CT Scan as Determined by the Investigator (Phase II) | 95.5 Percentage of responders |
Secondary
CR Rate at PRA Based on CT Only as Determined by the Investigator (Phase II)
Time frame: 6-8 weeks after C6D1 or last dose of study treatment
Population: The intent-to-treat (ITT) population consisted of all participants. Efficacy analyses for Arms A1, A2, and B were exploratory.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | CR Rate at PRA Based on CT Only as Determined by the Investigator (Phase II) | 50.0 Percentage of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | CR Rate at PRA Based on CT Only as Determined by the Investigator (Phase II) | 47.5 Percentage of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | CR Rate at PRA Based on CT Only as Determined by the Investigator (Phase II) | 31.8 Percentage of participants |
Secondary
Duration of Response (DOR) as Determined by the Investigator (Phase II)
DOR is defined as the time from the first occurrence of a documented objective response to disease progression or relapse as determined by the investigator, or death from any cause, whichever occurs first. The range values (min-max) are based on censored observations (if a participant did not experience disease progression or death prior to the end of the trial DOR was censored on the date of the last tumor assessment).
Time frame: Up to approximately 50 months
Population: The number of participants analyzed was the number of participants with a PR or CR in each arm. The range values (min-max) are based on censored observations (if a participant did not experience disease progression or death prior to the end of the trial DOR was censored on the date of the last tumor assessment). Efficacy analyses for Arms A1, A2, and B were exploratory.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Duration of Response (DOR) as Determined by the Investigator (Phase II) | NA Months |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Duration of Response (DOR) as Determined by the Investigator (Phase II) | NA Months |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Duration of Response (DOR) as Determined by the Investigator (Phase II) | NA Months |
Secondary
Event-free Survival (EFS) as Determined by the Investigator (Phase II)
EFS is defined as the time from randomization to the first occurrence of disease progression or relapse, as determined by the investigator, initiation of new anti-lymphoma therapy (NALT), or death from any cause, whichever occurs first. The range values (min-max) are based on censored observations (if a participant did not experience disease progression or death prior to the end of the trial DOR was censored on the date of the last tumor assessment).
Time frame: Up to 50 months
Population: Efficacy analyses for Arms A1, A2, and B were exploratory. The number of participants analyzed reflects the number of participants with the event. The range (min-max) values are based on censored observations (participants without a baseline-evaluable tumor assessment or documentation of NALT were censored at the date of randomization or first study treatment, plus 1 day).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Event-free Survival (EFS) as Determined by the Investigator (Phase II) | NA Months |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Event-free Survival (EFS) as Determined by the Investigator (Phase II) | NA Months |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Event-free Survival (EFS) as Determined by the Investigator (Phase II) | NA Months |
Secondary
Mosunetuzumab Serum Concentrations
Time frame: C1D1-C5D1
Population: Participants with at least one pharmacokinetic (PK) sample were included in analysis. Arms in which participants did not receive mosunetuzumab were not included in this endpoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D8 pre-dose | 0.0331 ug/mL | Geometric Coefficient of Variation 49 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C3D1 pre-dose | 0.458 ug/mL | Geometric Coefficient of Variation 36.3 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D15 pre-dose | 0.0866 ug/mL | Geometric Coefficient of Variation 47.9 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C2D1 2 hrs post-dose | 2.38 ug/mL | Geometric Coefficient of Variation 1.2 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C5D1 pre-dose | 0.426 ug/mL | Geometric Coefficient of Variation 51.7 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D8 post-dose | 0.342 ug/mL | Geometric Coefficient of Variation 18.8 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C4D1 post-dose | 3.24 ug/mL | Geometric Coefficient of Variation 31.3 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D8 2hrs post-dose | 0.32 ug/mL | Geometric Coefficient of Variation 28.5 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D2 24 hrs post-dose | 0.103 ug/mL | Geometric Coefficient of Variation 23.3 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C4D1 pre-dose | 0.502 ug/mL | Geometric Coefficient of Variation 36.9 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C3D1 post-dose | 3.37 ug/mL | Geometric Coefficient of Variation 23.4 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C2D1 pre-dose | 0.549 ug/mL | Geometric Coefficient of Variation 24.3 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D1 2 hrs post-dose | 0.152 ug/mL | Geometric Coefficient of Variation 27.8 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C2D1 post-dose | 2.86 ug/mL | Geometric Coefficient of Variation 7.2 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D15 post-dose | 2.83 ug/mL | Geometric Coefficient of Variation 22.6 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D1 post-dose | 0.157 ug/mL | Geometric Coefficient of Variation 22.1 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D15 2 hrs post-dose | 2.28 ug/mL | Geometric Coefficient of Variation 7.5 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D1 2 hrs post-dose | 0.163 ug/mL | Geometric Coefficient of Variation 25.8 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C3D1 pre-dose | 1.08 ug/mL | Geometric Coefficient of Variation 53.3 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C3D1 post-dose | 7.19 ug/mL | Geometric Coefficient of Variation 30.8 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D2 24 hrs post-dose | 0.112 ug/mL | Geometric Coefficient of Variation 8.1 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C5D1 pre-dose | 1.02 ug/mL | Geometric Coefficient of Variation 62 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D8 pre-dose | 0.0218 ug/mL | Geometric Coefficient of Variation 153.2 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D15 2 hrs post-dose | 5.66 ug/mL | Geometric Coefficient of Variation 38.7 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D8 post-dose | 0.427 ug/mL | Geometric Coefficient of Variation 36.2 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D1 post-dose | 0.181 ug/mL | Geometric Coefficient of Variation 26.7 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D8 2hrs post-dose | 0.409 ug/mL | Geometric Coefficient of Variation 50.1 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D15 pre-dose | 0.0884 ug/mL | Geometric Coefficient of Variation 52.8 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C4D1 post-dose | 7.38 ug/mL | Geometric Coefficient of Variation 26.3 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D15 post-dose | 5.71 ug/mL | Geometric Coefficient of Variation 38.6 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C2D1 pre-dose | 1.52 ug/mL | Geometric Coefficient of Variation 49.4 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C2D1 2 hrs post-dose | 7.33 ug/mL | Geometric Coefficient of Variation 44.7 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C2D1 post-dose | 6.75 ug/mL | Geometric Coefficient of Variation 42.2 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C4D1 pre-dose | 1.09 ug/mL | Geometric Coefficient of Variation 44.4 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C5D1 pre-dose | 0.33 ug/mL | Geometric Coefficient of Variation 176.6 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C4D1 pre-dose | 0.782 ug/mL | Geometric Coefficient of Variation 90 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D2 24 hrs post-dose | 0.0947 ug/mL | Geometric Coefficient of Variation 60.2 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C2D2 pre-dose | 1.37 ug/mL | Geometric Coefficient of Variation 38.6 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D15 post-dose | 5.72 ug/mL | Geometric Coefficient of Variation 44 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C3D1 post-dose | 6.66 ug/mL | Geometric Coefficient of Variation 41.3 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C3D1 pre-dose | 1.21 ug/mL | Geometric Coefficient of Variation 45.1 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C2D2 post-dose | 8.9 ug/mL | Geometric Coefficient of Variation 34.1 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C4D1 post-dose | 4.09 ug/mL | Geometric Coefficient of Variation 83 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D8 post-dose | 0.354 ug/mL | Geometric Coefficient of Variation 36.9 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C2D1 2 hrs post-dose | 7.65 ug/mL | Geometric Coefficient of Variation 35.1 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D8 2hrs post-dose | 0.349 ug/mL | Geometric Coefficient of Variation 43.1 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D15 2 hrs post-dose | 5.92 ug/mL | Geometric Coefficient of Variation 18.5 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D8 pre-dose | 0.0334 ug/mL | Geometric Coefficient of Variation 113.6 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D2 2 hrs post-dose | 0.145 ug/mL | Geometric Coefficient of Variation 80 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D15 pre-dose | 0.0911 ug/mL | Geometric Coefficient of Variation 57.7 |
| Group C: Phase II Mosunetuzumab + CHOP | Mosunetuzumab Serum Concentrations | C1D8 pre-dose | 0.0253 ug/mL | Geometric Coefficient of Variation 62.2 |
| Group C: Phase II Mosunetuzumab + CHOP | Mosunetuzumab Serum Concentrations | C1D15 2 hrs post-dose | 6.56 ug/mL | Geometric Coefficient of Variation 28.4 |
| Group C: Phase II Mosunetuzumab + CHOP | Mosunetuzumab Serum Concentrations | C1D1 post-dose | 0.155 ug/mL | Geometric Coefficient of Variation 34.1 |
| Group C: Phase II Mosunetuzumab + CHOP | Mosunetuzumab Serum Concentrations | C1D1 2 hrs post-dose | 0.151 ug/mL | Geometric Coefficient of Variation 28.1 |
| Group C: Phase II Mosunetuzumab + CHOP | Mosunetuzumab Serum Concentrations | C1D2 24 hrs post-dose | 0.096 ug/mL | Geometric Coefficient of Variation 35.7 |
| Group C: Phase II Mosunetuzumab + CHOP | Mosunetuzumab Serum Concentrations | C1D8 post-dose | 0.426 ug/mL | Geometric Coefficient of Variation 30.3 |
| Group C: Phase II Mosunetuzumab + CHOP | Mosunetuzumab Serum Concentrations | C1D8 2hrs post-dose | 0.388 ug/mL | Geometric Coefficient of Variation 27.6 |
| Group C: Phase II Mosunetuzumab + CHOP | Mosunetuzumab Serum Concentrations | C1D15 pre-dose | 0.0953 ug/mL | Geometric Coefficient of Variation 41.8 |
| Group C: Phase II Mosunetuzumab + CHOP | Mosunetuzumab Serum Concentrations | C1D15 post-dose | 7.13 ug/mL | Geometric Coefficient of Variation 27.7 |
| Group C: Phase II Mosunetuzumab + CHOP | Mosunetuzumab Serum Concentrations | C2D1 pre-dose | 1.67 ug/mL | Geometric Coefficient of Variation 32.1 |
| Group C: Phase II Mosunetuzumab + CHOP | Mosunetuzumab Serum Concentrations | C2D1 post-dose | 8.31 ug/mL | Geometric Coefficient of Variation 27.4 |
| Group C: Phase II Mosunetuzumab + CHOP | Mosunetuzumab Serum Concentrations | C2D1 2 hrs post-dose | 8.28 ug/mL | Geometric Coefficient of Variation 26.7 |
| Group C: Phase II Mosunetuzumab + CHOP | Mosunetuzumab Serum Concentrations | C3D1 pre-dose | 1.11 ug/mL | Geometric Coefficient of Variation 30.2 |
| Group C: Phase II Mosunetuzumab + CHOP | Mosunetuzumab Serum Concentrations | C3D1 post-dose | 7.3 ug/mL | Geometric Coefficient of Variation 39.2 |
| Group C: Phase II Mosunetuzumab + CHOP | Mosunetuzumab Serum Concentrations | C4D1 pre-dose | 1.03 ug/mL | Geometric Coefficient of Variation 33.9 |
| Group C: Phase II Mosunetuzumab + CHOP | Mosunetuzumab Serum Concentrations | C4D1 post-dose | 7.41 ug/mL | Geometric Coefficient of Variation 44 |
| Group C: Phase II Mosunetuzumab + CHOP | Mosunetuzumab Serum Concentrations | C5D1 pre-dose | 1.12 ug/mL | Geometric Coefficient of Variation 31.6 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C2D1 pre-dose | 1.46 ug/mL | Geometric Coefficient of Variation 62.8 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D1 post-dose | 0.132 ug/mL | Geometric Coefficient of Variation 73.2 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C4D1 pre-dose | 0.932 ug/mL | Geometric Coefficient of Variation 52 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D15 post-dose | 6.31 ug/mL | Geometric Coefficient of Variation 34.8 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D15 pre-dose | 0.102 ug/mL | Geometric Coefficient of Variation 47.7 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D8 post-dose | 0.376 ug/mL | Geometric Coefficient of Variation 38.8 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C5D1 pre-dose | 0.935 ug/mL | Geometric Coefficient of Variation 106.1 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C4D1 post-dose | 5.55 ug/mL | Geometric Coefficient of Variation 80.3 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D8 pre-dose | 0.0263 ug/mL | Geometric Coefficient of Variation 77 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C1D2 24 hrs post-dose | 0.0825 ug/mL | Geometric Coefficient of Variation 46.1 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C3D1 post-dose | 6.76 ug/mL | Geometric Coefficient of Variation 28.9 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C3D1 pre-dose | 0.885 ug/mL | Geometric Coefficient of Variation 43 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Mosunetuzumab Serum Concentrations | C2D1 post-dose | 7.69 ug/mL | Geometric Coefficient of Variation 38.3 |
Secondary
ORR at PRA Based on CT Only as Determined by the Investigator (Phase II)
ORR is defined as a CR or PR at the time of primary assessment based on CT only, as determined by the investigator.
Time frame: 6-8 weeks after C6D1 or last dose of study treatment
Population: The intent-to-treat (ITT) population consisted of all participants. Efficacy analyses for Arms A1, A2, and B were exploratory.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | ORR at PRA Based on CT Only as Determined by the Investigator (Phase II) | 85.0 Percentage of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | ORR at PRA Based on CT Only as Determined by the Investigator (Phase II) | 72.5 Percentage of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | ORR at PRA Based on CT Only as Determined by the Investigator (Phase II) | 81.8 Percentage of participants |
Secondary
Overall Response Rate (ORR) at PRA Based on PET-CT as Determined by the Investigator (Phase II)
ORR is defined as a CR or PR at the time of primary assessment based on PET-CT, as determined by the investigator.
Time frame: 6-8 weeks after C6D1 or last dose of study treatment
Population: The intent-to-treat (ITT) population consisted of all participants. Efficacy analyses for Arms A1, A2, and B were exploratory.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Overall Response Rate (ORR) at PRA Based on PET-CT as Determined by the Investigator (Phase II) | 87.5 Percentage of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Overall Response Rate (ORR) at PRA Based on PET-CT as Determined by the Investigator (Phase II) | 80.0 Percentage of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Overall Response Rate (ORR) at PRA Based on PET-CT as Determined by the Investigator (Phase II) | 77.3 Percentage of participants |
Secondary
PFS at 1 Year as Determined by the Investigator (Phase II)
PFS at 1 year is defined as the proportion of participants with disease progression or relapse as determined by the investigator, or death from any cause within 1 year of randomization.
Time frame: 1 year
Population: Efficacy analyses for Arms A1, A2, and B were exploratory.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | PFS at 1 Year as Determined by the Investigator (Phase II) | 77.47 Percentage of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | PFS at 1 Year as Determined by the Investigator (Phase II) | 70.83 Percentage of participants |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | PFS at 1 Year as Determined by the Investigator (Phase II) | 81.82 Percentage of participants |
Secondary
Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations
Time frame: C1D1-C6D1
Population: Participants with at least one pharmacokinetic (PK) sample were included in analysis. Arms in which participants did not receive polatuzumab vedotin were not included in this endpoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C5D1 pre-dose | 7.14 ng/mL | Geometric Coefficient of Variation 343.5 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C5D1 post-dose | 544 ng/mL | Geometric Coefficient of Variation 37.6 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C6D1 pre-dose | 11.8 ng/mL | Geometric Coefficient of Variation 476.6 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C2D1 pre-dose | 4.87 ng/mL | Geometric Coefficient of Variation 626 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C3D1 pre-dose | 19.2 ng/mL | Geometric Coefficient of Variation 58.7 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C3D1 post-dose | 144 ng/mL | Geometric Coefficient of Variation 112947.3 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C4D1 pre-dose | 16.8 ng/mL | Geometric Coefficient of Variation 79.6 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C2D1 post-dose | 656 ng/mL | Geometric Coefficient of Variation 21.1 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C4D1 post-dose | 783 ng/mL | Geometric Coefficient of Variation 26.5 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C1D1 post-dose | 620 ng/mL | Geometric Coefficient of Variation 54.5 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C1D2 pre-dose | 219 ng/mL | Geometric Coefficient of Variation 412.2 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C1D2 24hrs post-dose | 115 ng/mL | Geometric Coefficient of Variation 658.3 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C1D8 pre-dose | 23 ng/mL | Geometric Coefficient of Variation 1040.4 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C1D15 pre-dose | 8.22 ng/mL | Geometric Coefficient of Variation 550.4 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C5D1 pre-dose | 19 ng/mL | Geometric Coefficient of Variation 39.7 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C5D1 post-dose | 605 ng/mL | Geometric Coefficient of Variation 21.6 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C1D1 post-dose | 668 ng/mL | Geometric Coefficient of Variation 21.2 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C6D1 pre-dose | 21.2 ng/mL | Geometric Coefficient of Variation 34.7 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C2D1 post-dose | 653 ng/mL | Geometric Coefficient of Variation 18 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C1D15 pre-dose | 13.2 ng/mL | Geometric Coefficient of Variation 87.4 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C3D1 pre-dose | 15.8 ng/mL | Geometric Coefficient of Variation 39.5 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C4D1 post-dose | 614 ng/mL | Geometric Coefficient of Variation 15.4 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C3D1 post-dose | 544 ng/mL | Geometric Coefficient of Variation 90.7 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C1D2 24hrs post-dose | 275 ng/mL | Geometric Coefficient of Variation 28.2 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C4D1 pre-dose | 16.8 ng/mL | Geometric Coefficient of Variation 50.3 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C2D1 pre-dose | 6.81 ng/mL | Geometric Coefficient of Variation 80.1 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C1D8 pre-dose | 42 ng/mL | Geometric Coefficient of Variation 82 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C6D1 pre-dose | 17.3 ng/mL | Geometric Coefficient of Variation 40.8 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C2D1 pre-dose | 7.09 ng/mL | Geometric Coefficient of Variation 95.5 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C2D1 post-dose | 654 ng/mL | Geometric Coefficient of Variation 21 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C4D1 pre-dose | 15.6 ng/mL | Geometric Coefficient of Variation 41.4 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C1D1 post-dose | 584 ng/mL | Geometric Coefficient of Variation 23.1 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations | C4D1 post-dose | 696 ng/mL | Geometric Coefficient of Variation 24.1 |
Secondary
Polatuzumab Vedotin Serum Concentrations
Time frame: C2D1, C6D1
Population: Participants with at least one pharmacokinetic (PK) sample were included in analysis. Arms in which participants did not receive polatuzumab vedotin were not included in this endpoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Serum Concentrations | C2D1 pre-dose | 0.993 ug/mL | Geometric Coefficient of Variation 779.4 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Serum Concentrations | C6D1 pre-dose | 2.76 ug/mL | Geometric Coefficient of Variation 820.1 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Serum Concentrations | C2D1 pre-dose | 1.99 ug/mL | Geometric Coefficient of Variation 80.7 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Serum Concentrations | C6D1 pre-dose | 8.13 ug/mL | Geometric Coefficient of Variation 34.5 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Serum Concentrations | C2D1 pre-dose | 1.73 ug/mL | Geometric Coefficient of Variation 107.9 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Serum Concentrations | C6D1 pre-dose | 5.8 ug/mL | Geometric Coefficient of Variation 42 |
Secondary
Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations
Time frame: C1D1-C6D1
Population: Participants with at least one pharmacokinetic (PK) sample were included in analysis. Arms in which participants did not receive polatuzumab vedotin were not included in this endpoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C1D1 post-dose | 0.535 ng/mL | Geometric Coefficient of Variation 464.6 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C1D2 pre-dose | 1.94 ng/mL | Geometric Coefficient of Variation 114.2 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C1D2 24hrs post-dose | 3.3 ng/mL | Geometric Coefficient of Variation 97.8 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C1D8 pre-dose | 2.95 ng/mL | Geometric Coefficient of Variation 80.9 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C1D15 pre-dose | 0.604 ng/mL | Geometric Coefficient of Variation 113.3 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C2D1 pre-dose | 0.187 ng/mL | Geometric Coefficient of Variation 47.3 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C2D1 post-dose | 0.238 ng/mL | Geometric Coefficient of Variation 64 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C3D1 pre-dose | 0.168 ng/mL | Geometric Coefficient of Variation 92 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C3D1 post-dose | 0.111 ng/mL | Geometric Coefficient of Variation 173.9 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C4D1 pre-dose | 0.0491 ng/mL | — |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C4D1 post-dose | 0.0825 ng/mL | Geometric Coefficient of Variation 188.3 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C5D1 pre-dose | 0.0741 ng/mL | Geometric Coefficient of Variation 247 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C5D1 post-dose | 0.212 ng/mL | Geometric Coefficient of Variation 54.2 |
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C6D1 pre-dose | 0.0967 ng/mL | Geometric Coefficient of Variation 194.2 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C2D1 post-dose | 0.137 ng/mL | Geometric Coefficient of Variation 84 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C1D2 24hrs post-dose | 2.82 ng/mL | Geometric Coefficient of Variation 51.9 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C1D8 pre-dose | 1.27 ng/mL | Geometric Coefficient of Variation 93.6 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C5D1 post-dose | 0.17 ng/mL | Geometric Coefficient of Variation 38.1 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C1D15 pre-dose | 0.301 ng/mL | Geometric Coefficient of Variation 104.1 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C4D1 post-dose | 0.186 ng/mL | Geometric Coefficient of Variation 66.1 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C2D1 pre-dose | 0.0773 ng/mL | Geometric Coefficient of Variation 110.2 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C3D1 pre-dose | 0.146 ng/mL | Geometric Coefficient of Variation 96.9 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C5D1 pre-dose | 0.137 ng/mL | Geometric Coefficient of Variation 74.4 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C3D1 post-dose | 0.203 ng/mL | Geometric Coefficient of Variation 92.7 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C1D1 post-dose | 0.55 ng/mL | Geometric Coefficient of Variation 71.1 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C6D1 pre-dose | 0.142 ng/mL | Geometric Coefficient of Variation 63.8 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C4D1 pre-dose | 0.14 ng/mL | Geometric Coefficient of Variation 93.8 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C2D1 post-dose | 0.116 ng/mL | Geometric Coefficient of Variation 56.3 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C6D1 pre-dose | 0.0974 ng/mL | Geometric Coefficient of Variation 82.4 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C1D1 post-dose | 0.432 ng/mL | Geometric Coefficient of Variation 78.8 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C4D1 pre-dose | 0.106 ng/mL | Geometric Coefficient of Variation 88.9 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C4D1 post-dose | 0.164 ng/mL | Geometric Coefficient of Variation 43.6 |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations | C2D1 pre-dose | 0.0697 ng/mL | Geometric Coefficient of Variation 87 |
Secondary
Progression-free Survival (PFS) as Determined by the Investigator (Phase II)
PFS is defined as the time from randomization to the first occurrence of disease progression or relapse as determined by the investigator, or death from any cause, whichever occurs first. The earliest contributing event to PFS is reported. The range (min-max) values are based on censored observations (participants without a baseline-evaluable tumor assessment were censored at the date of randomization or first study treatment, plus 1 day).
Time frame: Up to approximately 50 months
Population: Efficacy analyses for Arms A1, A2, and B were exploratory. The number of participants analyzed reflects the number of participants with the event. The range (min-max) values are based on censored observations (participants without a baseline-evaluable tumor assessment were censored at the date of randomization or first study treatment, plus 1 day).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Progression-free Survival (PFS) as Determined by the Investigator (Phase II) | NA Months |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Progression-free Survival (PFS) as Determined by the Investigator (Phase II) | NA Months |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Progression-free Survival (PFS) as Determined by the Investigator (Phase II) | NA Months |
Secondary
Time to Deterioration in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale
Time frame: C1D1 through follow-up period (to begin 2 years after PRA or at the time of study drug discontinuation)
Population: The intent-to-treat (ITT) population consisted of all participants. Efficacy analyses for Arms A1, A2, and B were exploratory. Patient-reported outcomes (PROs) were evaluated only for Arm 1 and Arm 2 per protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Time to Deterioration in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale | NA Months |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Time to Deterioration in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale | 6.5 Months |
Secondary
Time to Deterioration in Physical Functioning and Fatigue as Measured by the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTC QLQ-C30)
Time frame: C1D1 through follow-up period (to begin 2 years after PRA or at the time of study drug discontinuation)
Population: The intent-to-treat (ITT) population consisted of all participants. Efficacy analyses for Arms A1, A2, and B were exploratory. Patient-reported outcomes (PROs) were evaluated only for Arm 1 and Arm 2 per protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized) | Time to Deterioration in Physical Functioning and Fatigue as Measured by the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTC QLQ-C30) | 2.3 Months |
| Arm 2: Phase II Rituximab + CHP-Pola (Randomized) | Time to Deterioration in Physical Functioning and Fatigue as Measured by the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTC QLQ-C30) | 2.3 Months |