Lymphoma
Conditions
Brief summary
This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of obinutuzumab + Atezo + Pola in participants with relapsed or refractory (RR) FL and rituximab + Atezo + Pola in participants with RR DLBCL. The study will include an initial dose-escalation phase designed to determine the recommended Phase 2 dose (RP2D) for Pola in this treatment combination, followed by an expansion phase in which Pola will be given at the RP2D. All participants will receive induction treatment with obinutuzumab + Atezo + Pola for 6 cycles. RR FL participants achieving a complete response (CR), partial response (PR), or stable disease (SD) at the end of induction (EOI) will receive maintenance treatment with obinutuzumab.
Interventions
Atezolizumab will be administered by intravenous (IV) infusion at a flat dose of 1200 milligram (mg) every 3 weeks (Q3W) on Day 1 of Cycles 2-6, given in 21-day cycles during induction treatment. NOTE: Atezolizumab treatment has been discontinued in all participants currently on study treatment.
DRUGObinutuzumab
Obinutuzumab will be administered by IV infusion at a flat dose of 1000 mg on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-6, given in 21-day cycles during induction treatment, and on Day 1 of every other month during maintenance treatment (1 cycle=21 days; infusion rate starts at 50 mg/hour (hr) and increases every 30 min to a maximum of 400 mg/hr).
DRUGPolatuzumab Vedotin
Polatuzumab vedotin will be administered by IV infusion. For relapsed or refractory FL either 1.4 mg/kilogram (kg) or 1.8 mg/kg (dose-escalation phase) and at RP2D (dose-expansion phase) on Day 1 of Cycles 1-6 will be given in 21-day cycles during induction treatment. For relapsed or refactory DLBCL, 1.8 mg/kg will be given during run-in phase and either 1.8 mg/kg or 1.4 mg/kg during the expansion phase (1 cycle=21 days; infusion rate starts with 90 min and decreases to 30 min).
DRUGRituximab
Rituximab will be administered by IV infusion at 375 mg/m˄2 on Day 1 of Cycles 1-6 during induction treatment (1 cycle-21 days; infusion rate starts with 50 mg/hr and increases every 30 min to a maximum of 400 mg/hr).
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 * For obinutuzumab + Atezo + Pola treatment group: relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-Cluster of Differentiation (CD)20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator * For rituximab + Atezo + Pola treatment group: relapsed or refractory DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody, in participants who are not eligible for second line combination (immuno-) chemotherapy and autologous stem-cell transplantation or who have failed second line combination (immuno-) chemotherapy or experienced disease progression following autologous stem-cell transplantation * Histologically documented CD20-positive lymphoma and fluorodeoxyglucose (FDG)-avid lymphoma (that is PET-positive lymphoma) with at least one bi-dimensionally measurable lesion * Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL * For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or to use contraceptive methods that result in a failure rate of less than (\<) 1% per year during the treatment period for greater than or equal to (\>=) 5 months after last dose of Atezo, \>= 12 months after last dose of rituximab, \>= 12 months after last dose of Pola, and \>= 18 months after last dose of obinutuzumab * For men: agreement to remain abstinent or to use contraceptive measures that result in a failure rate of \<1% per year during the treatment period and for at least 3 months after last dose of obinutuzumab, rituximab, and Atezo and for 5 months after last dose of Pola, and agreement to refrain from donating sperm during this same period
Exclusion criteria
* Grade 3b follicular lymphoma * History of transformation of indolent disease to DLBCL * Known CD20-negative status at relapse or progression; CNS lymphoma or leptomeningeal infiltration * Prior allogeneic stem cell transplantation (SCT), completion of autologous SCT within 100 days prior to Day 1 of Cycle 1 (D1C1) * Prior anti-cancer therapy including: Fludarabine or alemtuzumab within 12 months prior to D1C1; radioimmunoconjugate within 12 weeks prior to D1C1; monoclonal antibody or antibody drug conjugate (ADC) within 5 half-lives or 4 weeks prior to D1C1 ; radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks prior to D1C1; anti-programmed death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), anti-CD137/41-BB agonist, or anti-CD40 agonist antibodies * Treatment with systemic immunosuppressive medications, including but not limited to prednisone, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to D1C1 * History of solid organ transplantation and of severe allergic or anaphylactic reaction to humanized, chimeric, or murine monoclonal antibodies * Active infection; positive for hepatitis B surface agent (HbsAg), total hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at screening; known history of HIV positive status, progressive multifocal leukoencephalopathy (PML), autoimmune disease * Vaccination with a live virus vaccine or live attenuated vaccine within 28 days prior to D1C1 * Pre-existing Grade greater than (\>) 1 neuropathy * Major surgical procedure other than for diagnosis within 28 days prior to D1C1 * Inadequate hematologic function, renal function, and liver function * Pregnant or lactating women * Life expectancy \< 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With CR at EOI, as Determined by the Investigator on the Basis of Positron Emission Tomography and Computed Tomography (PET-CT) Scan | Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months) | Tumor response assessment was performed by the investigator according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake \</=mediastinum), or 3 (uptake \<mediastinum but \</=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of PET-CT Scans | Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months) | Tumor response assessment was performed by investigator according to modified Lugano classification using PET/CT scan. OR: a response of CR or PR. CR: a score of 1 (no uptake above background), 2 (uptake \</=mediastinum), or 3 (uptake \<mediastinum but \</=liver) with or without a residual mass on PET 5-PS, for lymph nodes & extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR with a score 4 (uptake moderately greater than \[\>\] liver) or 5 (uptake markedly \>liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population |
| Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of CT Scans Alone | Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months) | Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to \<= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. PR with \>= 50 percet decrease in SPD of up to six target measurable nodes and extranodal sites, a 5 mm x 5 mm default value when lesions were too small, 0 x0 mm value when lesions were no longer visible, actual measurements were used for nodes greater than 5 mm x 5 mm for lymph nodes & extralymphatic sites; absent/normal, regression for non-measured lesion; spleen enlargement regression by \> 50 percent; no new lesions; reduced residual uptake in bone marrow compared to baseline. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population. |
| Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone | Baseline up to 35 months | Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to \<= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. PR with \>= 50 percet decrease in SPD of up to six target measurable nodes and extranodal sites, a 5 mm x 5 mm default value when lesions were too small, 0 x0 mm value when lesions were no longer visible, actual measurements were used for nodes greater than 5 mm x 5 mm for lymph nodes & extralymphatic sites; absent/normal, regression for non-measured lesion; spleen enlargement regression by \> 50 percent; no new lesions; reduced residual uptake in bone marrow compared to baseline. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population. |
| Percentage of Participants With Adverse Events and Serious Adverse Events | Baseline up to 35 months | An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Grading was completed according to the CTCAE, version 4.0 for severity and tumor flare reactions were graded according to NCI CTCAE v3.0. |
| Serum Obinutuzumab Concentration | Pre-dose (0 hr) up to 35 months | pre-dose (0 hr), 30 min after EOI on Day 1 Cycle 1; pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycles 2, 4, 6; maintenance phase: pre-dose (within 5 hr) on Day 1 of Months 1, 7, 13, 19; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and decreases every 30 min to maximum of 400 mg/hr) |
| Serum Rituximab Concentration | Pre-dose (0 hr) up to 35 months | pre-dose (0 hr), 30 min after EOI on Day 1 Cycle 1; pre-dose (within 5 hr) on Day 1 of Cycles 2, 4; pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycle 6; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increases every 30 min to maximum of 400 mg/hr) |
| Percentage of Participants With CR at EOI, as Determined by Investigator on the Basis of CT Scans Alone | Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months) | Tumor response assessment was performed by investigator according to modified Lugano classification using computed tomography (CT) scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to \<= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population. |
| Serum Pola Concentration | Pre-dose (0 hr) up to 35 months | pre-dose (0 hr) on Day 1 Cycle 1; pre-dose (within 5 hr) on Day 1 of Cycles 2, 4; maintenance phase: pre-dose (within 5 hr) on Day 1 of Months 1; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 90 min and decreases to 30 min) |
| Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | Baseline up to 35 months | Pre-dose (0 hr) on Day 1 of Cycle 1, 6, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increased every 30 min to maximum of 400 mg/hr) |
| Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab | Baseline to 35 months | Pre-dose (0 hr) on Day 1 of Cycle 1, 2, 4, 6, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increased every 30 min to maximum of 400 mg/hr) |
| Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Baseline to 35 months | Pre-dose (0 hr) on Day 1 of Cycle 2, 3, 4, 6, Month 1, 4, 7, 13 and 19, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 60 min and decreases to 30 min) |
| Percentage of Participants With ATAs to Pola | Baseline to 35 months | Pre-dose (0 hr) on Day 1 of Cycle 1, 2, 4, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 90 min and decreases to 30 min) |
| Serum Atezo Concentration | Pre-dose (0 hr) up to 35 months | pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycles 2, 3, 4; pre-dose (within 5 hr) on Day 1 of Cycle 6; maintenance phase: pre-dose (within 5 hr) on Day 1 of Month 1; 30 min after EOI on Day 2 of Month 1; pre-dose (within 5 hr) on Day 1 of Month 4, 7, 13, 19; anytime during treatment discontinuation visit, 120 days after the last dose, and 1-2 years after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 60 min and decreases to 30 min) |
Countries
Germany, Poland, United States
Participant flow
Recruitment details
The study was conducted at 11 investigational centres in Germany (3), Poland (5) and USA (3).
Participants by arm
| Arm | Count |
|---|---|
| Dose-Escalation FL Cohort 1.4 mg During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 milligram (mg) of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and 1.4 mg/kilogram (kg) of pola on Day 1. The 1.4 mg/kg dose was cleared by an Internal Monitoring Committee (IMC) review and escalated to 1.8 mg/kg. This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. | 3 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 mg of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and pola was escalated to 1.8 mg/kg (on Day 1); once cleared by the IMC it was declared as the recommended phase 2 dose (RP2D). This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. | 10 |
| Safety Run-in and Expansion DLBCL Cohort For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants received a 375 mg/m\^2 IV of rituximab on Day 1 and on Day 1 of every other month during consolidation. Participants also received a 1.8 mg/kg IV of Pola on Day 1. Cycles 2-6: participants received 1200 mg of Atezo on Day 1. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. | 23 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 2 | 13 |
| Overall Study | Lost to Follow-up | 0 | 2 | 3 |
| Overall Study | Other | 0 | 2 | 0 |
| Overall Study | Physician Decision | 1 | 2 | 3 |
| Overall Study | Progressive Disease | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 3 |
Baseline characteristics
| Characteristic | Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg | Safety Run-in and Expansion DLBCL Cohort | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 4 Participants | 11 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 6 Participants | 12 Participants | 20 Participants |
| Age, Continuous | 52.3 Years STANDARD_DEVIATION 13.6 | 57.7 Years STANDARD_DEVIATION 11.7 | 64.3 Years STANDARD_DEVIATION 15.3 | 61.5 Years STANDARD_DEVIATION 14.5 |
| Race/Ethnicity, Customized Hispanic or Latino | 0 participants | 1 participants | 3 participants | 4 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 3 participants | 9 participants | 18 participants | 30 participants |
| Race/Ethnicity, Customized Unknown | 0 participants | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized White | 3 participants | 9 participants | 21 participants | 33 participants |
| Sex: Female, Male Female | 0 Participants | 4 Participants | 9 Participants | 13 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 14 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 2 / 10 | 13 / 23 |
| other Total, other adverse events | 3 / 3 | 10 / 10 | 15 / 21 |
| serious Total, serious adverse events | 0 / 3 | 4 / 10 | 2 / 21 |
Outcome results
Primary
Percentage of Participants With CR at EOI, as Determined by the Investigator on the Basis of Positron Emission Tomography and Computed Tomography (PET-CT) Scan
Tumor response assessment was performed by the investigator according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake \</=mediastinum), or 3 (uptake \<mediastinum but \</=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Time frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Population: Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With CR at EOI, as Determined by the Investigator on the Basis of Positron Emission Tomography and Computed Tomography (PET-CT) Scan | 33.33 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With CR at EOI, as Determined by the Investigator on the Basis of Positron Emission Tomography and Computed Tomography (PET-CT) Scan | 14.30 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With CR at EOI, as Determined by the Investigator on the Basis of Positron Emission Tomography and Computed Tomography (PET-CT) Scan | 12.50 Percentage of participants |
Secondary
Percentage of Participants With Adverse Events and Serious Adverse Events
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Grading was completed according to the CTCAE, version 4.0 for severity and tumor flare reactions were graded according to NCI CTCAE v3.0.
Time frame: Baseline up to 35 months
Population: The Safety Evaluable Population that includes patients who received at least one dose of any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Adverse Events and Serious Adverse Events | 100.00 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Adverse Events and Serious Adverse Events | 100.00 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With Adverse Events and Serious Adverse Events | 81.00 Percentage of participants |
Secondary
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo
Pre-dose (0 hr) on Day 1 of Cycle 2, 3, 4, 6, Month 1, 4, 7, 13 and 19, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 60 min and decreases to 30 min)
Time frame: Baseline to 35 months
Population: The Safety Evaluable Population for this outcome measure includes participants in the DLBCL cohort who received at least one dose of any study treatment. Participants in the FL 1.4 mg and FL 1.8 mg were not anazlyed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Atezo PK Immunogenicity Follow up (120D), negative | 0 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 4 Day 1, negative | 0 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 3 Day 1, negative | 0 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 6 Day 1, negative | 0 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Study drug completion, negative | 0 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Consolidation Month 1 Day 1, negative | 0 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 2 Day 1, positive | 0 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 3 Day 1, positive | 0 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 2 Day 1, negative | 0 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Study drug completion, negative | 0 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Atezo PK Immunogenicity Follow up (120D), negative | 0 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 3 Day 1, positive | 0 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 3 Day 1, negative | 0 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 2 Day 1, negative | 0 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 4 Day 1, negative | 0 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 6 Day 1, negative | 0 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 2 Day 1, positive | 0 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Consolidation Month 1 Day 1, negative | 0 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Atezo PK Immunogenicity Follow up (120D), negative | 100.0 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 2 Day 1, positive | 5.3 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 2 Day 1, negative | 94.7 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 3 Day 1, positive | 7.1 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 3 Day 1, negative | 92.9 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 6 Day 1, negative | 100.0 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Consolidation Month 1 Day 1, negative | 100.0 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Study drug completion, negative | 100.0 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo | Induction, Cycle 4 Day 1, negative | 100.0 Percentage of participants |
Secondary
Percentage of Participants With ATAs to Pola
Pre-dose (0 hr) on Day 1 of Cycle 1, 2, 4, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 90 min and decreases to 30 min)
Time frame: Baseline to 35 months
Population: The Safety Evaluable Population that includes patients who received at least one dose of any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With ATAs to Pola | 0 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With ATAs to Pola | 0 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With ATAs to Pola | 0 Percentage of participants |
Secondary
Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone
Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to \<= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. PR with \>= 50 percet decrease in SPD of up to six target measurable nodes and extranodal sites, a 5 mm x 5 mm default value when lesions were too small, 0 x0 mm value when lesions were no longer visible, actual measurements were used for nodes greater than 5 mm x 5 mm for lymph nodes & extralymphatic sites; absent/normal, regression for non-measured lesion; spleen enlargement regression by \> 50 percent; no new lesions; reduced residual uptake in bone marrow compared to baseline. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Time frame: Baseline up to 35 months
Population: Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone | Progressive disease | 33.3 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone | Stable disease | 33.3 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone | Complete response | 33.3 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone | Partial response | 0 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone | Not available | 0 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone | Stable disease | 14.3 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone | Complete response | 14.3 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone | Partial response | 42.9 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone | Progressive disease | 14.3 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone | Not available | 14.3 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone | Not available | 37.5 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone | Progressive disease | 31.3 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone | Complete response | 12.5 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone | Stable disease | 6.3 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone | Partial response | 12.5 Percentage of participants |
Secondary
Percentage of Participants With CR at EOI, as Determined by Investigator on the Basis of CT Scans Alone
Tumor response assessment was performed by investigator according to modified Lugano classification using computed tomography (CT) scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to \<= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Time frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Population: Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With CR at EOI, as Determined by Investigator on the Basis of CT Scans Alone | 0.00 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With CR at EOI, as Determined by Investigator on the Basis of CT Scans Alone | 57.14 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With CR at EOI, as Determined by Investigator on the Basis of CT Scans Alone | 12.50 Percentage of participants |
Secondary
Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab
Pre-dose (0 hr) on Day 1 of Cycle 1, 2, 4, 6, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increased every 30 min to maximum of 400 mg/hr)
Time frame: Baseline to 35 months
Population: The Safety Evaluable Population that includes patients who received at least one dose of any study treatment. (FL cohorts not applicable as rituximab was only administered in the Safety Run- in phase).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab | Induction Cycle 2 Day 1, negative | 94.4 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab | Induction Cycle 4 Day 1 | 100 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab | Baseline, positive | 5.6 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab | Baseline, negative | 94.4 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab | Induction Cycle 2 Day 1, positive | 5.6 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab | Induction Cycle 6 Day 1 | 100 Percentage of participants |
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab | Study drug completion | 100 Percentage of participants |
Secondary
Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab
Pre-dose (0 hr) on Day 1 of Cycle 1, 6, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increased every 30 min to maximum of 400 mg/hr)
Time frame: Baseline up to 35 months
Population: The Safety Evaluable Population that includes patients who received at least one dose of any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | 0 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | 0 Percentage of participants |
Secondary
Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of CT Scans Alone
Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to \<= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. PR with \>= 50 percet decrease in SPD of up to six target measurable nodes and extranodal sites, a 5 mm x 5 mm default value when lesions were too small, 0 x0 mm value when lesions were no longer visible, actual measurements were used for nodes greater than 5 mm x 5 mm for lymph nodes & extralymphatic sites; absent/normal, regression for non-measured lesion; spleen enlargement regression by \> 50 percent; no new lesions; reduced residual uptake in bone marrow compared to baseline. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Time frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Population: Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of CT Scans Alone | 33.33 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of CT Scans Alone | 57.14 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of CT Scans Alone | 25.00 Percentage of participants |
Secondary
Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of PET-CT Scans
Tumor response assessment was performed by investigator according to modified Lugano classification using PET/CT scan. OR: a response of CR or PR. CR: a score of 1 (no uptake above background), 2 (uptake \</=mediastinum), or 3 (uptake \<mediastinum but \</=liver) with or without a residual mass on PET 5-PS, for lymph nodes & extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR with a score 4 (uptake moderately greater than \[\>\] liver) or 5 (uptake markedly \>liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population
Time frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Population: Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalation FL Cohort 1.4 mg | Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of PET-CT Scans | 33.33 Percentage of participants |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of PET-CT Scans | 57.14 Percentage of participants |
| Safety Run-In Phase | Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of PET-CT Scans | 25.00 Percentage of participants |
Secondary
Serum Atezo Concentration
pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycles 2, 3, 4; pre-dose (within 5 hr) on Day 1 of Cycle 6; maintenance phase: pre-dose (within 5 hr) on Day 1 of Month 1; 30 min after EOI on Day 2 of Month 1; pre-dose (within 5 hr) on Day 1 of Month 4, 7, 13, 19; anytime during treatment discontinuation visit, 120 days after the last dose, and 1-2 years after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 60 min and decreases to 30 min)
Time frame: Pre-dose (0 hr) up to 35 months
Population: The Safety Evaluable Population that includes patients who received at least one dose of any study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-Escalation FL Cohort 1.4 mg | Serum Atezo Concentration | Maintenance Month 1 Day 1 Pre-dose | 100 mcg/mL | Standard Deviation 66 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Atezo Concentration | Induction Cycle 4 Day 1 Pre-dose | 139 mcg/mL | Standard Deviation 33.1 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Atezo Concentration | Maintenance Month 13 Pre-dose | 106 mcg/mL | Standard Deviation 83 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Atezo Concentration | Induction Cycle 6 Day 1 Pre-dose | 194 mcg/mL | Standard Deviation 67.7 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Atezo Concentration | Induction Cycle 4 Day 1 Post-dose | 462 mcg/mL | Standard Deviation 82 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Atezo Concentration | Maintenance Month 4 Pre-dose | 240 mcg/mL | Standard Deviation 101 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Atezo Concentration | Induction Cycle 2 Day 1 Pre-dose | NA mcg/mL | — |
| Dose-Escalation FL Cohort 1.4 mg | Serum Atezo Concentration | Maintenance Month 7 Pre-dose | 226 mcg/mL | Standard Deviation 134 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Atezo Concentration | Maintenance Month 1 Day 2 Post-dose | 577 mcg/mL | Standard Deviation 144 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Atezo Concentration | Induction Cycle 2 Day 1 Post-dose | 332 mcg/mL | Standard Deviation 56.7 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Atezo Concentration | Induction Cycle 3 Day 1 Pre-dose | 86.9 mcg/mL | Standard Deviation 28.8 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Atezo Concentration | PK and Immunogenicity followup 120D | 61.4 mcg/mL | Standard Deviation 60.3 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Atezo Concentration | PK and Immunogenicity followup 1 Year | NA mcg/mL | — |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Atezo Concentration | Maintenance Month 7 Pre-dose | 221 mcg/mL | Standard Deviation 90.5 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Atezo Concentration | Induction Cycle 2 Day 1 Pre-dose | NA mcg/mL | — |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Atezo Concentration | Induction Cycle 3 Day 1 Pre-dose | 78.7 mcg/mL | Standard Deviation 18.4 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Atezo Concentration | Induction Cycle 4 Day 1 Pre-dose | 125 mcg/mL | Standard Deviation 47.3 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Atezo Concentration | Induction Cycle 4 Day 1 Post-dose | 450 mcg/mL | Standard Deviation 136 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Atezo Concentration | Induction Cycle 6 Day 1 Pre-dose | 181 mcg/mL | Standard Deviation 112 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Atezo Concentration | Maintenance Month 1 Day 1 Pre-dose | 70.7 mcg/mL | Standard Deviation 55.5 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Atezo Concentration | Maintenance Month 1 Day 2 Post-dose | 473 mcg/mL | Standard Deviation 177 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Atezo Concentration | Maintenance Month 4 Pre-dose | 140 mcg/mL | Standard Deviation 141 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Atezo Concentration | Study drug completion or early discontinuation | 127 mcg/mL | — |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Atezo Concentration | PK and Immunogenicity followup 120D | 16.8 mcg/mL | Standard Deviation 26.8 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Atezo Concentration | Induction Cycle 2 Day 1 Post-dose | 365 mcg/mL | Standard Deviation 80.7 |
| Safety Run-In Phase | Serum Atezo Concentration | Consolidation Month 1 Day 2 Post-dose | 503 mcg/mL | Standard Deviation 214 |
| Safety Run-In Phase | Serum Atezo Concentration | Study drug completion or early discontinuation | 93.0 mcg/mL | Standard Deviation 14.2 |
| Safety Run-In Phase | Serum Atezo Concentration | Induction Cycle 2 Day 1 Post-dose | 355 mcg/mL | Standard Deviation 78.8 |
| Safety Run-In Phase | Serum Atezo Concentration | Induction Cycle 4 Day 1 Post-dose | 489 mcg/mL | Standard Deviation 131 |
| Safety Run-In Phase | Serum Atezo Concentration | Induction Cycle 4 Day 1 Pre-dose | 139 mcg/mL | Standard Deviation 56.4 |
| Safety Run-In Phase | Serum Atezo Concentration | PK and Immunogenicity followup 120D | 19.9 mcg/mL | Standard Deviation 0.778 |
| Safety Run-In Phase | Serum Atezo Concentration | Induction Cycle 6 Day 1 Pre-dose | 180 mcg/mL | Standard Deviation 90.6 |
| Safety Run-In Phase | Serum Atezo Concentration | Induction Cycle 3 Day 1 Pre-dose | 79.7 mcg/mL | Standard Deviation 30.6 |
| Safety Run-In Phase | Serum Atezo Concentration | Consolidation Month 1 Day 1 Pre-dose | 132 mcg/mL | Standard Deviation 43.3 |
| Safety Run-In Phase | Serum Atezo Concentration | Induction Cycle 2 Day 1 Pre-dose | NA mcg/mL | — |
Secondary
Serum Obinutuzumab Concentration
pre-dose (0 hr), 30 min after EOI on Day 1 Cycle 1; pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycles 2, 4, 6; maintenance phase: pre-dose (within 5 hr) on Day 1 of Months 1, 7, 13, 19; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and decreases every 30 min to maximum of 400 mg/hr)
Time frame: Pre-dose (0 hr) up to 35 months
Population: The Safety Evaluable Population that includes patients who received at least one dose of any study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-Escalation FL Cohort 1.4 mg | Serum Obinutuzumab Concentration | Induction cycle 1 Day 1 Pre-dose | NA mcg/mL | — |
| Dose-Escalation FL Cohort 1.4 mg | Serum Obinutuzumab Concentration | Induction cycle 1 Day 1 Post-dose | 308 mcg/mL | Standard Deviation 41.6 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Obinutuzumab Concentration | Induction cycle 2 Day 1 Pre-dose | 351 mcg/mL | Standard Deviation 81.3 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Obinutuzumab Concentration | Induction cycle 2 Day 1 Post-dose | 616 mcg/mL | Standard Deviation 115 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Obinutuzumab Concentration | Induction cycle 6 Day 1 Pre-dose | 288 mcg/mL | Standard Deviation 123 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Obinutuzumab Concentration | Induction cycle 4 Day 1 Pre-dose | 433 mcg/mL | Standard Deviation 322 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Obinutuzumab Concentration | Induction cycle 4 Day 1 Post-dose | 583 mcg/mL | Standard Deviation 189 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Obinutuzumab Concentration | Induction cycle 6 Day 1 Post-dose | 514 mcg/mL | Standard Deviation 121 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Obinutuzumab Concentration | Maintenance Month 1 Day 1 Pre-dose | 221 mcg/mL | — |
| Dose-Escalation FL Cohort 1.4 mg | Serum Obinutuzumab Concentration | Maintenance Month 7 Pre-dose | 90.4 mcg/mL | Standard Deviation 58.8 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Obinutuzumab Concentration | Maintenance Month 13 Pre-dose | 78.8 mcg/mL | Standard Deviation 42.8 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Obinutuzumab Concentration | PK and Immunogenicity follow up | 110 mcg/mL | Standard Deviation 120 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Obinutuzumab Concentration | Maintenance Month 7 Pre-dose | 83.8 mcg/mL | Standard Deviation 59.6 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Obinutuzumab Concentration | Induction cycle 6 Day 1 Pre-dose | 308 mcg/mL | Standard Deviation 194 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Obinutuzumab Concentration | Induction cycle 1 Day 1 Pre-dose | NA mcg/mL | — |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Obinutuzumab Concentration | PK and Immunogenicity follow up | 15.4 mcg/mL | Standard Deviation 3.2 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Obinutuzumab Concentration | Induction cycle 1 Day 1 Post-dose | 295 mcg/mL | Standard Deviation 171 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Obinutuzumab Concentration | Induction cycle 6 Day 1 Post-dose | 605 mcg/mL | Standard Deviation 161 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Obinutuzumab Concentration | Induction cycle 2 Day 1 Pre-dose | 403 mcg/mL | Standard Deviation 143 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Obinutuzumab Concentration | Maintenance Month 13 Pre-dose | 158 mcg/mL | Standard Deviation 1.41 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Obinutuzumab Concentration | Induction cycle 2 Day 1 Post-dose | 672 mcg/mL | Standard Deviation 130 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Obinutuzumab Concentration | Induction cycle 4 Day 1 Post-dose | 619 mcg/mL | Standard Deviation 160 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Obinutuzumab Concentration | Maintenance Month 1 Day 1 Pre-dose | 171 mcg/mL | Standard Deviation 131 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Obinutuzumab Concentration | Study drug completion or early discontinuation | 37.2 mcg/mL | — |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Obinutuzumab Concentration | Induction cycle 4 Day 1 Pre-dose | 311 mcg/mL | Standard Deviation 177 |
Secondary
Serum Pola Concentration
pre-dose (0 hr) on Day 1 Cycle 1; pre-dose (within 5 hr) on Day 1 of Cycles 2, 4; maintenance phase: pre-dose (within 5 hr) on Day 1 of Months 1; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 90 min and decreases to 30 min)
Time frame: Pre-dose (0 hr) up to 35 months
Population: The Safety Evaluable Population that includes patients who received at least one dose of any study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-Escalation FL Cohort 1.4 mg | Serum Pola Concentration | Maintenance Month 1 Day 1 Pre-dose | 1.30 mcg/mL | Standard Deviation 0.696 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Pola Concentration | Induction Cycle 4 Day 1 Pre-dose | 4.73 mcg/mL | Standard Deviation 2.1 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Pola Concentration | Induction Cycle 2 Day 1 Pre-dose | 2.54 mcg/mL | Standard Deviation 0.918 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Pola Concentration | Induction Cycle 2 Day 1 Pre-dose | 2.62 mcg/mL | Standard Deviation 1.22 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Pola Concentration | Pre Day 120 Follow-up | 0.136 mcg/mL | — |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Pola Concentration | Induction Cycle 1 Day 1 Pre-dose | 0.847 mcg/mL | — |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Pola Concentration | Induction Cycle 4 Day 1 Pre-dose | 4.27 mcg/mL | Standard Deviation 1.63 |
| Dose-Escalation and Expansion FL Cohort 1.8 mg | Serum Pola Concentration | Maintenance Month 1 Day 1 Pre-dose | 1.63 mcg/mL | Standard Deviation 1.75 |
| Safety Run-In Phase | Serum Pola Concentration | Study drug completion or early discontinuation | 0.716 mcg/mL | Standard Deviation 0.2 |
| Safety Run-In Phase | Serum Pola Concentration | Induction Cycle 4 Day 1 Pre-dose | 4.92 mcg/mL | Standard Deviation 2.65 |
| Safety Run-In Phase | Serum Pola Concentration | Pre Day 120 Follow-up | 2.91 mcg/mL | — |
| Safety Run-In Phase | Serum Pola Concentration | Induction Cycle 1 Day 1 Pre-dose | 35.9 mcg/mL | — |
| Safety Run-In Phase | Serum Pola Concentration | Induction Cycle 2 Day 1 Pre-dose | 3.37 mcg/mL | Standard Deviation 3.6 |
Secondary
Serum Rituximab Concentration
pre-dose (0 hr), 30 min after EOI on Day 1 Cycle 1; pre-dose (within 5 hr) on Day 1 of Cycles 2, 4; pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycle 6; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increases every 30 min to maximum of 400 mg/hr)
Time frame: Pre-dose (0 hr) up to 35 months
Population: The Safety Evaluable Population that includes patients who received at least one dose of any study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-Escalation FL Cohort 1.4 mg | Serum Rituximab Concentration | Induction Cycle 6 Day 1 Pre-dose | 101 mcg/mL | Standard Deviation 45.5 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Rituximab Concentration | Induction Cycle 1 Day 1 Pre-dose | 30.4 mcg/mL | Standard Deviation 28.8 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Rituximab Concentration | Induction Cycle 1 Day 1 Post-dose | 197 mcg/mL | Standard Deviation 56.9 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Rituximab Concentration | Induction Cycle 2 Day 1 Pre-dose | 43.5 mcg/mL | Standard Deviation 28.7 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Rituximab Concentration | Induction Cycle 4 Day 1 Pre-dose | 84.8 mcg/mL | Standard Deviation 35.7 |
| Dose-Escalation FL Cohort 1.4 mg | Serum Rituximab Concentration | Induction Cycle 6 Day 1 Post-dose | 239 mcg/mL | Standard Deviation 42.8 |