Clinical Trial Results:
A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination with Atezolizumab Plus Polatuzumab Vedotin in Patients with Relapsed or Refractory Follicular Lymphoma and Rituximab in Combination with Atezolizumab Plus Polatuzumab Vedotin in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Summary
|
|
EudraCT number |
2015-004845-25 |
Trial protocol |
DE PL |
Global end of trial date |
07 Oct 2019
|
Results information
|
|
Results version number |
v4(current) |
This version publication date |
16 Dec 2020
|
First version publication date |
21 Sep 2019
|
Other versions |
v1 , v2 , v3 |
Version creation reason |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
BO29561
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02729896 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
F. Hoffmann-La Roche AG
|
||
Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
|
||
Public contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
|
||
Scientific contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, globa.trial_information@roche.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
07 Oct 2019
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
07 Oct 2019
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
To Evaluate the Safety and Efficacy of Obinutuzumab in Combination with Atezolizumab plus
Polatuzumab Vedotin in Patients with Relapsed or Refractory Follicular Lymphoma and Rituximab in
Combination with Atezolizumab plus Polatuzumab Vedotin in Patients with Relapsed or Refractory Diffuse Large B Cell Lymphoma.
|
||
Protection of trial subjects |
All study subjects were required to read and sign an Informed Consent Form.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Nov 2016
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Germany: 11
|
||
Country: Number of subjects enrolled |
Poland: 14
|
||
Country: Number of subjects enrolled |
United States: 11
|
||
Worldwide total number of subjects |
36
|
||
EEA total number of subjects |
25
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
20
|
||
From 65 to 84 years |
15
|
||
85 years and over |
1
|
|
|||||||||||||||||||||||||||||||||||||||||
Recruitment
|
|||||||||||||||||||||||||||||||||||||||||
Recruitment details |
- | ||||||||||||||||||||||||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||||||||||||||||||||||||
Screening details |
56 patients were screened and 36 patients enrolled and dosed in the study. | ||||||||||||||||||||||||||||||||||||||||
Period 1
|
|||||||||||||||||||||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||||||||||||||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||||||
Arms
|
|||||||||||||||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||||||||||||||||||||||
Arm title
|
Dose-Escalation FL Cohort 1.4 mg | ||||||||||||||||||||||||||||||||||||||||
Arm description |
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. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Atezolizumab
|
||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
1200 mg
|
||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Obinutuzumab
|
||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
1000 mg
|
||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Polatuzumab Vedotin
|
||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
1.4 mg
|
||||||||||||||||||||||||||||||||||||||||
Arm title
|
Dose-Escalation and Expansion FL Cohort 1.8 mg | ||||||||||||||||||||||||||||||||||||||||
Arm description |
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. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Atezolizumab
|
||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
1200 mg
|
||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Obinutuzumab
|
||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
1000 mg
|
||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Polatuzumab Vedotin
|
||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
1.8 mg
|
||||||||||||||||||||||||||||||||||||||||
Arm title
|
Safety Run-in and Expansion DLBCL Cohort | ||||||||||||||||||||||||||||||||||||||||
Arm description |
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. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Atezolizumab
|
||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
1200 mg
|
||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Polatuzumab Vedotin
|
||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
1.4 mg or 1.8 mg
|
||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Rituximab
|
||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
375 mg/m˄2
|
||||||||||||||||||||||||||||||||||||||||
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Dose-Escalation FL Cohort 1.4 mg
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Dose-Escalation and Expansion FL Cohort 1.8 mg
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Safety Run-in and Expansion DLBCL Cohort
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Dose-Escalation FL Cohort 1.4 mg
|
||
Reporting group description |
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. | ||
Reporting group title |
Dose-Escalation and Expansion FL Cohort 1.8 mg
|
||
Reporting group description |
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. | ||
Reporting group title |
Safety Run-in and Expansion DLBCL Cohort
|
||
Reporting group description |
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. |
|
|||||||||||||||||
End point title |
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 [1] | ||||||||||||||||
End point description |
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.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
|
||||||||||||||||
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint is only reporting the percentage of participants |
|||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of Participants with CR at EOI, as Determined by Investigator on the Basis of CT Scans Alone | ||||||||||||||||
End point description |
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.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of Participants with Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of PET-CT Scans | ||||||||||||||||
End point description |
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
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of Participants with Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of CT Scans Alone | ||||||||||||||||
End point description |
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.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
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 | ||||||||||||||||||||||||||||||||||||
End point description |
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.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline up to 35 months
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of Participants with Adverse Events and Serious Adverse Events | ||||||||||||||||
End point description |
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.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline up to 35 months
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Serum Obinutuzumab Concentration [2] | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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). 99999 represents the upper limit of confidence interval was not estimable due to the low number of subjects within events.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-dose (0 hr) up to 35 months
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only arms treated with Obinutuzumab were included in this endpoint |
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Serum Rituximab Concentration [3] | ||||||||||||||||||||
End point description |
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)
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Pre-dose (0 hr) up to 35 months
|
||||||||||||||||||||
Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only arms treated with Rituximab were included in this endpoint |
|||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Serum Atezo Concentration | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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). 99999 represents the upper limit of confidence interval was not estimable due to the low number of subjects within events.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-dose (0 hr) up to 35 months
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Serum Pola Concentration | ||||||||||||||||||||||||||||||||||||||||
End point description |
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). 99999 represents the upper limit of confidence interval was not estimable due to the low number of subjects within events.
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-dose (0 hr) up to 35 months
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Percentage of Participants with Human Anti-Human Antibodies (HAHAs) to Obinutuzumab [4] | |||||||||
End point description |
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)
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Baseline up to 35 months
|
|||||||||
Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only arms treated with Obinutuzumab were included in this endpoint |
||||||||||
|
||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||
End point title |
Percentage of Participants with Human Anti-Chimeric Antibodies (HACAs) to Rituximab [5] | ||||||||||||||||||||||
End point description |
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)
|
||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||
End point timeframe |
Baseline to 35 months
|
||||||||||||||||||||||
Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only arms treated with Rituximab were included in this endpoint |
|||||||||||||||||||||||
|
|||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Atezo | ||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline to 35 months
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants with ATAs to Pola | ||||||||||||
End point description |
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)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to 35 months
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From randomization up to 35 months
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
All adverse events that occurred on or after the first dose of study treatment are summarized by mapped term, appropriate thesaurus levels, and National Cancer Institute Common Terminology Criteria (NCI CTCAE) v4.0 grade. All-Cause Mortality is reported for the ITT population.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Dose-Escalation FL Cohort 1.4 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Dose-Escalation and Expansion FL Cohort 1.8 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Safety Run-in and Expansion DLBCL Cohort
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [16] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [17] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [18] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [19] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [20] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [21] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [22] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [23] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [24] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [25] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [26] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [27] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [28] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [29] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [30] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [31] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [32] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [33] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [34] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [35] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [36] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [37] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [38] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [39] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [40] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [41] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [42] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [43] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [44] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [45] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [46] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [47] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [48] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [49] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [50] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [51] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [52] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [53] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [54] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [55] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [56] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [57] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [58] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [59] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [60] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [61] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [62] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [63] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [64] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [65] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [66] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [67] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [68] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [69] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [70] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [71] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [72] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [73] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [74] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [75] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [76] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [77] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [78] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [79] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [80] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [81] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [82] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [83] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [84] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [85] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [86] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [87] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [88] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [89] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [90] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [91] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [92] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [93] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [94] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [95] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [96] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [97] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [98] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [99] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [100] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [101] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [102] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [103] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [104] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [105] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [106] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [107] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [108] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [109] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [110] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). [111] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: In the DLBCL Safety Run in phase 23 subjects enrolled in study. However two patients did not receive any study treatment and therefore were not included in the Safety Evaluable population (n=21). |
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
14 Jan 2016 |
Version 2: The protocol has been revised to update the DLT window and to clarify inclusion/exclusion and stopping criteria.
Additional minor changes have been made to improve clarity and consistency. |
||
28 Jun 2016 |
Version 3: The inclusion criterion on contraception requirements for women of childbearing potential has been revised to include the duration of contraception for atezolizumab and polatuzumab vedotin. Enrollment rules into the dose escalation phase have been updated, for patients’ safety considerations. A sequential enrollment instead of a parallel enrollment will be used for each of the two dosing groups, |
||
17 Nov 2016 |
Version 4: “Immune-mediated” was revised to “immune-related” when referring to adverse events. Cut-off date for Atezolizumab was changed to 15 December 2016. The title has been revised. Study treatment has been modified to include Rituximab (RO0452294) in combination with atezolizumab plus polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma. |
||
04 May 2017 |
Version 5: The protocol has been modified to prohibit use of the term "sudden death" on the Adverse Event eCRF, unless it is combined with the presumed cause of death. Language has been added to clarify that the Sponsor will review all protocol
deviations, and clarification has been added that prospective requests to deviate from the protocol are not allowed. |
||
21 Dec 2017 |
Version 6: Clinical Data) has been updated with the most recent efficacy and safety results from Study GO29383. Aligned the protocol with the current atezolizumab Investigator’s Brochure,
Version 10. A few exclusion criteria updated. |
||
01 May 2018 |
Version 7: The study design and treatment schedule has been revised to reflect discontinuation of atezolizumab in patients still receiving study treatment. In addition, the post-induction (rituximab + atezolizumab consolidation) treatment phase has been removed from the treatment schedule (rituximab + atezolizumab + polatuzumab vedotin [R+Atezo+Pola] treatment group) of patients with RR DLBCL. |
||
07 Nov 2018 |
Version 8: Lists of risks for atezolizumab-associated adverse events were revised to include nephritis. Regular Internal Monitoring Committee assessments stopped taking place as no new safety signals identified. Language was changed allowing patients still under treatment to enter the extension study. Medical Moniter information was updated. Survival follow-up period for assessment of new anti-lymphoma treatment re-added. PK sampling one year after last dose for polatuzumab vedotin was removed. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
A safety signal was observed during the study in two patients in the R/R FL cohort. As a result, enrollment was permanently discontinued and atezolizumab was discontinued for all patients still receiving study treatment. |