Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Percentage of Participants With CR at EOI Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans |
CR at EOI was assessed by the IRC according to modified Lugano Response Criteria (MLRC) for Malignant Lymphoma 2014 using PET-CT scan. Per MLRC, CR was defined as complete metabolic response (MR) in lymph nodes and extra lymphatic sites (ELS) with a score of 1, 2, or 3, with or without a residual mass on PET 5-point scale (5-PS), where 1=no uptake above background; 2= uptake =mediastinum; 3= uptake > mediastinum but = liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions. No new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point. |
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21 days) |
|
| Primary |
FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
An AE was defined as 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 AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any new disease or worsening of an existing disease were also considered as AEs. An SAE was defined as any AE that was fatal, life threatening, requires prolonged inpatient hospitalization, resulted in significant disability or resulted in a congenital anomaly to a mother exposed to study treatment. AEs and SAEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0). Percentages have been rounded off to the first decimal point. |
From study start to 24 months after last dose of study drug (approximately 56 months) |
|
| Primary |
DLBCL Cohorts: Percentage of Participants With AEs and SAEs |
An AE was defined as 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 AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any new disease or worsening of an existing disease were also considered as AEs. An SAE was defined as any AE that was fatal, life threatening, requires prolonged inpatient hospitalization, resulted in significant disability or resulted in a congenital anomaly to a mother exposed to study treatment. AEs and SAEs were reported based on the NCI-CTCAE, v4.0. Percentages have been rounded off to the first decimal point. |
From study start to 3 months after last dose of study drug (approximately 21 months) |
|
| Primary |
Number of Participants With Dose-Limiting Toxicities (DLTs) |
DLT=any one of the events that occurred in first treatment cycle & per the investigator was related to study treatment. Any AE that lead to a delay of > 14 days in start of next treatment cycle; Any Grade 3/4 non-hematologic AE with few exceptions; Any increase in hepatic transaminase >3×baseline(BL) & increase in direct bilirubin >2×upper limit of normal (ULN), without any findings of cholestasis/jaundice/signs of hepatic dysfunction & in absence of other contributory factors; Grade1 alanine transaminase (ALT)/aspartate transaminase (AST) elevation at BL as result of liver metastases, only a Grade =3 elevation, also =3×BL lasting >7 days; Hematologic AE meeting protocol specified criteria. Events were graded per NCI CTCAE v4.0. Grade 1:Mild; asymptomatic/mild symptoms; Grade 2:Moderate;minimal,local/non-invasive intervention indicated; Grade 3:Severe/medically significant, but not immediately life-threatening; Grade 4:Life-threatening consequences/urgent intervention indicated. |
Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase |
|
| Primary |
RP2D of Polatuzumab Vedotin |
RP2D was defined as the highest dose with acceptable toxicity as determined from dose-escalation phase. The RP2D of polatuzumab vedotin when given in combination with fixed dose of obinutuzumab in participants with FL was determined. |
Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase |
|
| Primary |
RP2D of Venetoclax |
RP2D was defined as the highest dose with acceptable toxicity as determined from dose-escalation phase. The RP2D of venetoclax when given in combination with fixed dose of polatuzumab vedotin in participants with FL and DLBCL was determined. |
Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase |
|
| Secondary |
Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans |
CR at EOI was assessed by Investigator according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake = mediastinum; 3=uptake > mediastinum but = liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions; no evidence of FDG-avid disease in bone marrow. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point. |
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days) |
|
| Secondary |
Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone |
CR at EOI was determined by IRC according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to = 1.5 centimeters (cm) in longest transverse diameter (LDi) and no ELS of disease; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, immunohistochemistry (IHC) negative. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point. |
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days) |
|
| Secondary |
Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of CT Scans Alone |
CR at EOI was determined by Investigator according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to = 1.5 cm in LDi and no ELS of disease; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. 90% CI for percentage of responders was calculated using Clopper-Pearson method. |
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days) |
|
| Secondary |
Percentage of Participants With Objective Response (OR) at EOI, Determined by an IRC on the Basis of PET and CT Scans |
OR=percentage of participants with CR or PR as assessed by the IRC according to MLRC. Per MLRC CR based on PET-CT=complete MR in lymph nodes & ELS with score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake = mediastinum; 3=uptake> mediastinum but = liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions; no new lesions & no evidence of FDG-avid disease in bone marrow. PR based on PET-CT=partial MR in lymph nodes & ELS with score of 4 or 5 with reduced uptake compared with baseline & residual masses of any size: at interim (suggest responding disease) or at end of treatment (indicate residual disease), residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed). 90% CI was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point. |
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days) |
|
| Secondary |
Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of PET and CT Scans |
OR=percentage of participants with CR or PR as assessed by the IRC according to MLRC. Per MLRC CR based on PET-CT=complete MR in lymph nodes & ELS with score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake = mediastinum; 3=uptake> mediastinum but = liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions;no new lesions & no evidence of FDG-avid disease in bone marrow. PR based on PET-CT=partial MR in lymph nodes & ELS with score of 4 or 5 with reduced uptake compared with baseline & residual masses of any size: at interim (suggest responding disease) or at end of treatment (indicate residual disease), residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed). 90% CI was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point. |
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days) |
|
| Secondary |
Percentage of Participants With OR at EOI, Determined by an IRC on the Basis of CT Scans Alone |
OR was defined as the percentage of participants with CR or PR, as assessed by the IRC based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to = 1.5 cm in LDi and no ELS of disease; organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with =50% decrease in the sum of the products of greatest diameters (SPD) of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by =50% in length beyond normal, no new sites of lesions. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point. |
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days) |
|
| Secondary |
Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of CT Scans Alone |
OR was defined as the percentage of participants with CR or PR, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to = 1.5 cm in LDi and no ELS of disease; organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with =50% decrease in the SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by =50% in length beyond normal, no new sites of lesions. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point. |
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days) |
|
| Secondary |
Percentage of Participants With Best Overall Response (BOR) of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone |
BOR=CR or PR as assessed by investigator per CT per MLRC. Per MLRC, CR based on CT was defined as a complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to = 1.5 cm in LDi and no ELS of disease; organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with =50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by =50% in length beyond normal, no new sites of lesions. Percentages have been rounded off to the first decimal point. |
Up to every 6 months until disease progression, the start of new anti-lymphoma treatment, or the end of the study, whichever occurs first (approximately 77 months) |
|
| Secondary |
Observed Serum Obinutuzumab Concentration |
|
Pre-dose & 0.5 hours post-dose on Day 1 Cycles 1, 2, 4, & 6; and pre-dose on Day 1 of Months 2, 8, 14, 20; study drug discontinuation, Day 120 &1 year post-last dose (up to approximately 40 months) (1 cycle = 21 days) |
|
| Secondary |
Observed Serum Rituximab Concentration |
|
Pre-dose and 0.5 hours post-dose on Day 1 of Cycles 1 and 6; pre-dose on Day 1 of Cycles 2 and 4; (1 cycle = 21 days) |
|
| Secondary |
Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin |
Total antibody is an analyte of polatuzumab vedotin. |
Pre-dose on Day 1 of Cycles 1, 2 and 4; study drug discontinuation visit; Day 120 and 1 year post-last dose (up to approximately 16 months) (1 cycle=21 days) |
|
| Secondary |
Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) |
acMMAE is an analyte of polatuzumab vedotin. |
Pre-dose and 0.5 hours post-dose on Day 1 of Cycles 1, 2 and 4; post-dose on Days 8 and 15 of Cycle 1; predose on Day 1 of Cycle 6 (1 cycle=21 days) |
|
| Secondary |
Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE |
MMAE is an analyte of polatuzumab vedotin. |
Pre-dose and 0.5 hours post-dose on Day 1 of Cycles 1, 2 and 4; post-dose on Days 8 and 15 of Cycle 1; predose on Day 1 of Cycle 6 (1 cycle=21 days) |
|
| Secondary |
Observed Plasma Venetoclax Concentration |
|
Pre-dose and 4 hours post-dose on Day 1 Cycle 1, pre-dose & 2, 4, 6, & 8 hours post-dose on Day 1 Cycle 2, pre-dose & 4hours post-dose on Day 1 Cycle 4 & pre-dose on Day 1 Cycle 6; (1 cycle = 21 days) |
|
| Secondary |
Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab |
The number of participants with positive results for HAHAs, also called anti-drug antibodies (ADAs) against obinutuzumab at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result. |
Baseline up to approximately 2 years after last dose (up to approximately 56 months) |
|
| Secondary |
Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin |
The number of participants with positive results for ATAs, also called ADAs against polatuzumab vedotin at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. |
Baseline up to 1 year post last dose (up to approximately 16 months) |
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