Clinical Trial Results:
A Phase IB/II Study Evaluating the Safety and Efficacy of Atezolizumab in Combination With Either Obinutuzumab Plus Bendamustine or Obinutuzumab Plus CHOP in Patients with Follicular Lymphoma or Rituximab Plus CHOP in Patients With Diffuse Large B-Cell Lymphoma
Summary
|
|
EudraCT number |
2015-001364-19 |
Trial protocol |
IT |
Global end of trial date |
08 May 2020
|
Results information
|
|
Results version number |
v2(current) |
This version publication date |
12 May 2021
|
First version publication date |
25 Apr 2019
|
Other versions |
v1 |
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 |
BO29563
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02596971 | ||
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, global.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 |
08 May 2020
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
08 May 2020
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
A Study of Atezolizumab in Combination With Either Obinutuzumab Plus Bendamustine or Obinutuzumab Plus (+) Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Participants With Follicular Lymphoma (FL) or Rituximab + CHOP in Participants With Diffuse Large B-Cell Lymphoma (DLBCL)
|
||
Protection of trial subjects |
Each subject, or the subject's representative, signed an informed consent form prior to screening.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
22 Dec 2015
|
||
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 |
Australia: 14
|
||
Country: Number of subjects enrolled |
Italy: 16
|
||
Country: Number of subjects enrolled |
United States: 61
|
||
Worldwide total number of subjects |
91
|
||
EEA total number of subjects |
16
|
||
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) |
61
|
||
From 65 to 84 years |
30
|
||
85 years and over |
0
|
|
|||||||||||||||||||||||||
Recruitment
|
|||||||||||||||||||||||||
Recruitment details |
The study was conducted at 15 sites in 3 countries (Italy, Australia, and USA). | ||||||||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||||||||
Screening details |
Out of the 117 subjects who were screened for this study, 91 subjects were enrolled to either FL treatment cohort (Atezo-G-Benda, Atezo-G-CHOP) or DLBCL cohort (Atezo-R-CHOP) and 26 subjects failed screening. | ||||||||||||||||||||||||
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
|
Atezo-G-Benda Cohort (Safety Run-In and Expansion Phases) | ||||||||||||||||||||||||
Arm description |
Safety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Atezolizumab
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
RO5541267; Tecentriq
|
||||||||||||||||||||||||
Pharmaceutical forms |
Solution for infusion
|
||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||
Dosage and administration details |
Atezolizumab 840 milligrams (mg) intravenously (IV) on Days 1 and 15 of Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1, during maintenance treatment.
|
||||||||||||||||||||||||
Investigational medicinal product name |
Obinutuzumab
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
GA101, RO5072759
|
||||||||||||||||||||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||
Dosage and administration details |
Obinutuzumab administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6, during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1, during maintenance treatment.
|
||||||||||||||||||||||||
Investigational medicinal product name |
Bendamustine
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||
Dosage and administration details |
Bendamustine administered at a dose of 90 milligrams per square meter (mg/m^2) IV on Days 1 and 2 of Cycles 1-6, during induction treatment.
|
||||||||||||||||||||||||
Arm title
|
Atezo-G-CHOP Cohort (Safety Run-In Phase) | ||||||||||||||||||||||||
Arm description |
Safety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, obinutuzumab, and CHOP during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (q2m) for 24 months, during maintenance treatment. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Atezolizumab
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
RO5541267; Tecentriq
|
||||||||||||||||||||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||
Dosage and administration details |
Atezolizumab 1200 mg IV on Day 1 Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1.
|
||||||||||||||||||||||||
Investigational medicinal product name |
Obinutuzumab
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
GA101, RO5072759
|
||||||||||||||||||||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||
Dosage and administration details |
Obinutuzumab administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6 during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1 during maintenance treatment.
|
||||||||||||||||||||||||
Investigational medicinal product name |
Cyclophosphamide
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Powder for solution for infusion
|
||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||
Dosage and administration details |
Cyclophosphamide 750 milligrams per square metre (mg/m^2), administered intravenously (IV) on Day 1 of each 21-day cycle.
|
||||||||||||||||||||||||
Investigational medicinal product name |
Doxorubicin
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Powder for solution for infusion
|
||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||
Dosage and administration details |
Doxorubicin will be administered at a dose of 50 mg/m^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.
|
||||||||||||||||||||||||
Investigational medicinal product name |
Prednisone
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||
Dosage and administration details |
Prednisone will be administered at a dose of 40 mg/m^2 orally on Days 1-5 of Cycle 1-6/8, during induction treatment. Prednisolone may be given if prednisone is unavailable. The 40 mg/m^2 dose of prednisone on Day 1 will be replaced by oral corticosteroids given as premedication on Day 1 of Cycle 1 (and subsequent cycles).
|
||||||||||||||||||||||||
Arm title
|
Atezo-R-CHOP Cohort (Expansion Phase) | ||||||||||||||||||||||||
Arm description |
Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Atezolizumab
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
RO5541267; Tecentriq
|
||||||||||||||||||||||||
Pharmaceutical forms |
Solution for infusion
|
||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||
Dosage and administration details |
Atezolizumab 1200 mg IV on Day 1 Cycles 2-8, during induction treatment, followed by 1200 mg IV on Day 1 of Cycles 9-25.
|
||||||||||||||||||||||||
Investigational medicinal product name |
Cyclophosphamide
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Powder for solution for infusion
|
||||||||||||||||||||||||
Routes of administration |
Intraventricular use , Intravenous use
|
||||||||||||||||||||||||
Dosage and administration details |
Cyclophosphamide will be administered at a dose of 750 mg/m^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.
|
||||||||||||||||||||||||
Investigational medicinal product name |
Prednisone
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||
Dosage and administration details |
Prednisone will be administered at a dose of 40 mg/m^2 orally on Days 1-5 of Cycle 1-6/8, during induction treatment. Prednisolone may be given if prednisone is unavailable. The 40 mg/m^2 dose of prednisone on Day 1 will be replaced by oral corticosteroids given as premedication on Day 1 of Cycle 1 (and subsequent cycles).
|
||||||||||||||||||||||||
Investigational medicinal product name |
Doxorubicin
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Powder for solution for infusion
|
||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||
Dosage and administration details |
Doxorubicin will be administered at a dose of 50 mg/m^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.
|
||||||||||||||||||||||||
Investigational medicinal product name |
Rituximab
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||
Dosage and administration details |
Participants with previously untreated DLBCL will receive rituximab at a dose of 375 mg/m^2 IV on Day 1 of Cycle 1-8, during induction treatment.
|
||||||||||||||||||||||||
Investigational medicinal product name |
Vincristine
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Solution for infusion
|
||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||||||
Dosage and administration details |
Vincristine will be administered at a dose of 1.4 mg/m^2 (maximum 2 mg) IV on Day 1 of Cycle 1-6/8, during induction treatment.
|
||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Atezo-G-Benda Cohort (Safety Run-In and Expansion Phases)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Safety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Atezo-G-CHOP Cohort (Safety Run-In Phase)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Safety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, obinutuzumab, and CHOP during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (q2m) for 24 months, during maintenance treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Atezo-R-CHOP Cohort (Expansion Phase)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Atezo-G-Benda Cohort (Safety Run-In and Expansion Phases)
|
||
Reporting group description |
Safety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase. | ||
Reporting group title |
Atezo-G-CHOP Cohort (Safety Run-In Phase)
|
||
Reporting group description |
Safety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, obinutuzumab, and CHOP during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (q2m) for 24 months, during maintenance treatment. | ||
Reporting group title |
Atezo-R-CHOP Cohort (Expansion Phase)
|
||
Reporting group description |
Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment. |
|
|||||||||||||
End point title |
Percentage of Participants With Complete Response (CR) at End of Induction (EOI), as Determined by the Independent Review Committee (IRC) Using Modified Lugano 2014 Criteria [1] [2] | ||||||||||||
End point description |
Primary end point was positron emission tomography (PET) CR at EOI by IRC according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake less than or equal to [</=] mediastinum), or 3 (uptake less than [<] mediastinum but </=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow; and normal/immunohistochemistry (IHC)-negative bone marrow morphology. All positron emission tomography (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 |
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: Results were reported descriptively and were not planned to be analyzed for statistically significant differences between groups. [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: Results were reported descriptively and were not planned to be analyzed for statistically significant differences between groups. |
|||||||||||||
|
|||||||||||||
Notes [3] - 2 subjects excluded from Atezo-G-Benda cohort due to diagnosis of r/r FL. [4] - 2 subjects excluded as they were excluded prior to Cycle 2 and were not treated with atezolizumab. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants With Adverse Events [5] | ||||||||||||
End point description |
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable 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. Preexisting conditions which worsen during a study are also considered as adverse events.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Baseline up to approximately 4 years
|
||||||||||||
Notes [5] - 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 is an adverse event endpoint and did not report statistics. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants With CR at EOI, as Determined by the Investigator Using Lugano 2014 Criteria [6] | ||||||||||||
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% CI for percentage of responders was calculated using Clopper-Pearson method. All positron emission tomography (PET) evaluable 1L FL and 1L DLBCL subjects with at least one dose of atezolizumab were included in efficacy population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to approximately 6 months
|
||||||||||||
Notes [6] - 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: Results were reported descriptively and were not planned to be analyzed for statistically significant differences between groups. |
|||||||||||||
|
|||||||||||||
Notes [7] - 2 subjects excluded from Atezo-G-Benda cohort due to diagnosis of r/r FL. [8] - 2 subjects excluded as they were excluded prior to Cycle 2 and were not treated with atezolizumab. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants With CR at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria [9] | ||||||||||||
End point description |
Complete response according to the modified Cheson 2007 criteria using PET/CT scan: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. All positron emission tomography (PET) evaluable 1L FL and 1L DLBCL subjects with at least one dose of atezolizumab were included in efficacy population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to approximately 6 months
|
||||||||||||
Notes [9] - 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: Results were reported descriptively and were not planned to be analyzed for statistically significant differences between groups. |
|||||||||||||
|
|||||||||||||
Notes [10] - 2 subjects excluded from Atezo-G-Benda cohort due to diagnosis of r/r FL. [11] - 2 subjects excluded as they were excluded prior to Cycle 2 and were not treated with atezolizumab. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants With CR at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria [12] | ||||||||||||
End point description |
Complete response according to modified Cheson 2007 criteria using PET/CT scan: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If bone marrow was involved by lymphoma prior to treatment, infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of other nodes, liver, or spleen; with exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. All positron emission tomography (PET) evaluable 1L FL and 1L DLBCL subjects with at least one dose of atezolizumab were included in efficacy population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to approximately 6 months
|
||||||||||||
Notes [12] - 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: Results were reported descriptively and were not planned to be analyzed for statistically significant differences between groups. |
|||||||||||||
|
|||||||||||||
Notes [13] - 2 subjects excluded from Atezo-G-Benda cohort due to diagnosis of r/r FL. [14] - 2 subjects excluded as they were excluded prior to Cycle 2 and were not treated with atezolizumab. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria [15] | ||||||||||||
End point description |
Objective response: having CR or PR as assessed according to the modified response criteria for iNHL (Modified Cheson et al, 2007). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. All positron emission tomography (PET) evaluable 1L FL and 1L DLBCL subjects with at least one dose of atezolizumab were included in efficacy population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to approximately 6 months
|
||||||||||||
Notes [15] - 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: Results were reported descriptively and were not planned to be analyzed for statistically significant differences between groups. |
|||||||||||||
|
|||||||||||||
Notes [16] - 2 subjecnts excluded from Atezo-G-Benda cohort due to diagnosis of r/r FL. [17] - 2 subjects excluded as they were excluded prior to Cycle 2 and were not treated with atezolizumab. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria [18] | ||||||||||||
End point description |
Objective response: having CR or PR as assessed according to the modified response criteria for iNHL (Modified Cheson et al, 2007). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. All positron emission tomography (PET) evaluable 1L FL and 1L DLBCL subjects with at least one dose of atezolizumab were included in efficacy population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to approximately 6 months
|
||||||||||||
Notes [18] - 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: Results were reported descriptively and were not planned to be analyzed for statistically significant differences between groups. |
|||||||||||||
|
|||||||||||||
Notes [19] - 2 subjects excluded from Atezo-G-Benda cohort due to diagnosis of r/r FL. [20] - 2 subjects excluded as they were excluded prior to Cycle 2 and were not treated with atezolizumab. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Lugano 2014 Criteria [21] | ||||||||||||
End point description |
Tumor response assessment was performed by IRC according to modified Lugano classification using PET/CT scan. OR defined as 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/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. PR: 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 positron emission tomography (PET) evaluable 1L FL and 1L DLBCL subjects with at least one dose of atezolizumab were included in efficacy population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to approximately 6 months
|
||||||||||||
Notes [21] - 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: Results were reported descriptively and were not planned to be analyzed for statistically significant differences between groups. |
|||||||||||||
|
|||||||||||||
Notes [22] - 2 subjects excluded from Atezo-G-Benda cohort due to diagnosis of r/r FL. [23] - 2 subjects excluded as they were excluded prior to Cycle 2 and were not treated with atezolizumab. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Lugano 2014 Criteria [24] | ||||||||||||
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 positron emission tomography (PET) evaluable 1L FL and 1L DLBCL subjects with at least one dose of atezolizumab were included in efficacy population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to approximately 6 months
|
||||||||||||
Notes [24] - 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: Results were reported descriptively and were not planned to be analyzed for statistically significant differences between groups. |
|||||||||||||
|
|||||||||||||
Notes [25] - 2 subjects excluded from Atezo-G-Benda cohort due to diagnosis of r/r FL. [26] - 2 subjects excluded as they were excluded prior to Cycle 2 and were not treated with atezolizumab. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants With Best Response of CR or PR During Study, as Determined by Investigator Using Modified Cheson 2007 Criteria [27] | ||||||||||||
End point description |
CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. Only Atezo-G-Benda and Atezo-R-Chop cohorts were evaluated for efficacy.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to approximately 4 years (assessed at Baseline, 6 to 8 weeks after Day [D] 1 of Cycle [Cy] 6 or 8 (1Cy: 21 or 28 days), then every 2 months up to 24 months, at 35 days of last dose, and at every 3 months post-treatment follow-up [up 4 years])
|
||||||||||||
Notes [27] - 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: Results were reported descriptively and were not planned to be analyzed for statistically significant differences between groups. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Observed Serum Obinutuzumab Concentration [28] | ||||||||||||||||||||||||
End point description |
Predose time point was "any time prior to dose" for Cycle 1 and "within 5 hour prior to dose" for other cycles (Cycles 2,5,6) and for Months 1 to 24 during maintenance phase. Infusion duration for administration of first infusion should begin at an initial rate of 50 milligrams per hour (mg/hour). If no reaction occurs, increase the infusion rate in 100 mg/hour increments every 30 minutes to a maximum of 400 mg/hour.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Induction: Predose, 0.5 hour (h) postinfusion on D1 of Cy1,2,5,6 (1Cy: 21/28 days); Maintenance: Predose, 0.5h postinfusion on Day 1 of Month 1,3,7,15,23; 120 days & 1 year of last dose or at treatment discontinuation (up to 4 years)
|
||||||||||||||||||||||||
Notes [28] - 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: This is a pharmacokinetic endpoint and did not report statistics. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Observed Serum Atezolizumab Concentration | ||||||||||||||||||||||||||||||||||||
End point description |
Atezo-G-Benda: Induction:Predose on D1 of Cy5,6 & D1,15 of Cy2,3 (1Cy:21/28 days), Cy2D1:0.5h postinfusion; Maintenance:Predose on D1 of Month 1,2,4,7,15,23, Month 2 D1: 0.5h postinfusion; 120 days & 1 year of last dose or at treatment discontinuation (up to 4 years); Atezo-G-CHOP: Induction:Predose on D1 of Cy2,3,5,6 (1Cy:21 days), Cy2D1:0.5h postinfusion; Maintenance:Predose on D1 of Month 1,2,3,4,7,15,23, Month 2 D1: 0.5h postinfusion; 120 days & 1 year of last dose or at treatment discontinuation (up to 4 years). Predose time point was "within 5 hour prior to dose" for Cy2,3,5,6 during induction phase and for Months 1 to 24 during maintenance phase. infusion length: 30-60 minutes. 0 represents no data was collected at that cycle.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Atezo-R-CHOP: Predose on D1 of Cy2,3,5,8,9,10,11,12,16,20,25 (1Cy:21 days), 0.5h postinfusion of D1 of Cy2,9; at 120 days & 1 year of last dose or at treatment discontinuation (up to 4 years)
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Observed Serum Rituximab Concentration [29] | ||||||||||||||||
End point description |
Predose time point was "any time prior to dose" for Cycle 1 and "within 5 hour prior to dose" for other cycles (Cycles 2,5,8) during induction phase and for Months 1 to 24 during maintenance phase. Infusion duration for administration of first infusion should begin at an initial rate of 50 mg/hour. If no infusion-related or hypersensitivity reaction occurs, increase the infusion rate in 50 mg/hour increments every 30 minutes to a maximum of 400 mg/hour. If no reaction occurs, increase the infusion rate in 100 mg/hour increments every 30 minutes to a maximum of 400 mg/hour.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Predose, 0.5h postinfusion on D1 of Cy1,2,5,8 (1Cy: 21 days); at 120 days and 1 year after last rituximab dose or at treatment discontinuation (up to 4 years)
|
||||||||||||||||
Notes [29] - 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: This is a pharmacokinetic endpoint and did not report statistics. |
|||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab [30] | ||||||||||||||||||||
End point description |
Induction: Predose (any time prior to dose) on D1 of Cy1,5,6 (1Cy: 21/28 days); Maintenance: Predose (any time prior to dose) on D1 of Month 1; at 120 days and 1 year of last obinutuzumab dose or at treatment discontinuation (up to 4 years)
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline up to approximately 4 years
|
||||||||||||||||||||
Notes [30] - 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: Results were reported descriptively and were not planned to be analyzed for statistically significant differences between groups. |
|||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||
End point title |
Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab [31] | ||||||||||||||||||||||
End point description |
Induction: Predose (any time prior to dose) on D1 of Cy2,3,5,8 (1Cy: 21 days); Maintenance: Predose (any time prior to dose) on D1 of Month 1; at 120 days and 1 year of last rituximab dose or at treatment discontinuation (up to 4 years)
|
||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||
End point timeframe |
Baseline up to approximately 4 years
|
||||||||||||||||||||||
Notes [31] - 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: Results were reported descriptively and were not planned to be analyzed for statistically significant differences between groups. |
|||||||||||||||||||||||
|
|||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab | ||||||||||||||||||||||||||||||||||||
End point description |
Atezo-G-CHOP: Induction: Predose on D1 of Cy2,3,5,6 (1 Cy: 21 days); Maintenance: Predose on D1 of Month 1,2,4,7,15,23; at 120 days and 1 year of last atezolizumab dose or at treatment discontinuation (up to 4 years); Atezo-R-CHOP: Predose on D1 of Cy 2,3,5,8,16,25 (1 Cy: 21 days); at 120 days and 1 year of last atezolizumab dose or at treatment discontinuation (up to 4 years). Predose time point was "any time prior to dose" for Cycles 2,3,5,6,8 during induction phase, for Cycles 16,25 during consolidation treatment, and for Months 1 to 24 during maintenance phase. Atezo-G-Benda: Induction: Predose on D1 of Cy2,3,5,6 (1Cy: 28 days), Cy3D15: Predose; ; Maintenance: Predose on D1 of Month 1,4,7,15,23; at 120 days and 1 year of last atezolizumab dose or at treatment discontinuation (up to 4 years). The percentage of participants with positive results for ATAs to atezolizumab at baseline and at post-baseline time points are reported.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline up to approximately 4 years
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Baseline up to approximately 4 years
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
The safety population is defined as all patients who received at least one dose of the study medication.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Atezo-G-Benda (Safety Run-In and Expansion Phases)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Safety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Atezo-G-CHOP (Safety Run-In Phase)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Safety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, obinutuzumab, and CHOP during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (q2m) for 24 months, during maintenance treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Atezo-R-CHOP (Expansion Phase)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
23 Oct 2015 |
MPDL3280A was changed to atezolizumab throughout the protocol. The management of gastrointestinal, dermatologic, endocrine, pulmonary toxicity, hepatotoxicity, potential pancreatic or ocular events, and other immune mediated adverse events was updated. Guidance on investigations for the differential diagnosis of Systemic immune activation (SIA) was added. An exclusion criterion was added: “Known history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug induced pneumonitis or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) was allowed.” The exclusion criterion related to infections was clarified as follows: “Active bacterial, viral, fungal, or other infection or any major episode of infection requiring treatment with IV antibiotics within 4 weeks of Day 1 of Cycle 1”. The use of receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor (denosumab) was updated. Clarifications were made on the use of vaccines. The exclusion criterion related to prior treatment in relapse or refractory FL subjects (enrolled in safety run-in) was clarified. The administration sequence of the monoclonal antibodies and bendamustine in the Atezo-G-Benda treatment group was clarified. The administration sequence of the monoclonal antibodies and bendamustine in the Atezo-G-Benda treatment group was clarified. |
||
07 Sep 2016 |
Further enrollment into the atezolizumab in combination with obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) treatment group at the end of the safety run-in phase is stopped. In the expansion phase, subjects with previously untreated diffuse large B-cell lymphoma (DLBCL) will receive atezolizumab in combination with rituximab plus CHOP. The rationale for this change is based on results from the Phase III BO21005/GOYA study showing that the addition of obinutuzumab to CHOP chemotherapy in subjects with previously untreated DLBCL did not improve the primary endpoint progression-free survival (PFS) compared with the standard regimen of rituximab plus CHOP chemotherapy. Obinutuzumab exposure data has been updated. Guidance for the administration of atezolizumab on Day 15 for the atezolizumab in combination with obinutuzumab plus bendamustine treatment group has been clarified.
Atezolizumab can be given on Day 15 of Cycles 2−6 regardless of cytopenia. The rationale for this update to the guidance is based on the mechanism of action of atezolizumab in conjunction with the available clinical experience showing minimal cytopenic effect of atezolizumab as a single agent, with an incidence of neutropenia of < 0.1%. Pharmacokinetic (PK) sampling schedule has been updated to include the “after
atezolizumab infusion” serum atezolizumab PK samples at certain timepoints as well as to clarify the sampling time windows. |
||
26 May 2017 |
The classification of second malignancies was changed from a selected adverse event to adverse event of special interest to more closely monitor this adverse event. Conditions for resuming study treatment in case of Grade ≥ 3 laboratory abnormalities was clarified. The list of adverse events of special interest for atezolizumab was updated. Language was modified to clarify the induction treatment with atezolizumab and CHOP. "Influenza-like illness" was added as an adverse event of special interest immediately reportable to the Sponsor. The protocol was modified to prohibit use of the term "sudden death" on the Adverse Event eCRF, unless it was combined with the presumed cause of death (e.g., "sudden cardiac death"). |
||
22 Dec 2017 |
Rationale for Treatment Combination section has been updated with the most recent efficacy and safety results from Study GO29383. Risks Associated with Obinutuzumab) has been updated to reflect recent updates to the Obinutuzumab treatment: Hypersensitivity reactions with delayed onset (e.g., serum sickness) have been added to previous warns related to hypersensitivity with immediate onset. The following observation has been added to warnings related to infections: In FL studies, a high incidence of infections was observed in all phases of the studies, including follow-up, with the highest incidence seen in maintenance. Section 5.1.3 (Risks Associated with Atezolizumab) have been revised to remove detailed presentation of the risks associated with atezolizumab. Section 5.1.7 (Management of Specific Adverse Events) management guidelines for atezolizumab-associated adverse events have been updated. |
||
07 Nov 2018 |
Lists of risks for atezolizumab and guidelines for managing participants who experienced atezolizumab-associated adverse events was revised to include nephritis; regular Internal Monitoring Committee assessments would no longer take place as no new safety signals were identified with atezolizumab in
combination with obinutuzumab plus CHOP or with atezolizumab in combination with rituximab plus CHOP. Ad hoc meetings could be called at the discretion of the Medical Monitor in case of new safety signals; Language regarding post-trial access was changed allowing particpants still under study treatment to enter an extension study in case there was an early closure of Study BO29563; Medical Monitor information was updated. |
||
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. | |||
Development of the atezolizumab combination treatment was discontinued as there was insufficient evidence regarding the additive efficacy of this therapy. |