Non-Hodgkin's Lymphoma
Conditions
Brief summary
This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment with obinutuzumab, polatuzumab vedotin, and venetoclax in participants with relapsed or refractory FL, and with rituximab, polatuzumab vedotin, and venetoclax in participants with DLBCL. Participants with FL who achieve complete response (CR), partial response (PR), or stable disease (SD) at the end of induction therapy will receive post-induction treatment with obinutuzumab and venetoclax, and participants with DLBCL who achieve CR or PR at the end of induction (EOI) will receive post-induction treatment with rituximab and venetoclax.
Interventions
DRUGObinutuzumab
Participants will receive a fixed dose of obinutuzumab, 1000 milligrams (mg) via intravenous (IV) infusion to be given on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6. Cycle length will be 21 days. For eligible participants, post-induction treatment may be given at a dose of 1000 mg via IV infusion on Day 1 of every other month (starting from Month 2) for up to 24 months, until disease progression or unacceptable toxicity.
DRUGRituximab
Participants will receive a fixed dose of rituximab, 375 milligrams per square meter (mg/m\^2) via IV infusion to be given on Day 1 of Cycles 1 to 6. Cycle length will be 21 days. For eligible participants, post-induction treatment may be given at a dose of 375 mg/m\^2 via IV infusion on Day 1 of every other month (starting from Month 2) for up to 8 months, until disease progression or unacceptable toxicity.
DRUGPolatuzumab Vedotin
Participants will receive polatuzumab vedotin via IV infusion at doses of 1.4 or 1.8 milligrams per kilogram (mg/kg) (for FL), and 1.8 mg/kg (for DLBCL) on Day 1 of each 21-day cycle for up to 18 weeks during induction treatment. Polatuzumab vedotin will not be given during the post-induction period.
DRUGVenetoclax
Participants will receive venetoclax film-coated tablets at doses of 200, 400, 600, or 800 mg (for FL), and 400, 600, or 800 mg (for DLBCL) on Days 1 to 21 of each 21-day cycle. Post-induction venetoclax may continue for up to 8 months, until disease progression or unacceptable toxicity.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * For obinutuzumab + polatuzumab vedotin + venetoclax treatment group, relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-cluster of differentiation 20 (CD20) (anti-CD20) monoclonal antibody (mAb) and for which no other more appropriate treatment option exists, as determined by the investigator * For rituximab + polatuzumab vedotin + venetoclax treatment group, relapsed or refractory DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 mAb and for which no curative option exists as determined by the investigator * At least one bidimensionally measurable lesion
Exclusion criteria
* Known CD20-negative status at relapse or progression * Prior allogeneic stem cell transplantation (SCT), or autologous SCT within 100 days prior to Day 1 of Cycle 1 * Grade 3b FL * History of transformation of indolent disease to DLBCL * Current use of systemic corticosteroids greater than (\>) 20 mg prednisone per day (or equivalent); or prior anti-cancer therapy to include: radioimmunoconjugate within 12 weeks; mAb or antibody-drug conjugate within 4 weeks; or radiotherapy/chemotherapy/hormone therapy/targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1 * Central nervous system (CNS) disease * Active infection * Actual or potential cytochrome P450 (CYP) 3A interactions including: requirement for warfarin; use of strong and moderate CYP3A inhibitors or inducers within 7 days prior to first dose of venetoclax; or consumption of grapefruit, Seville oranges, or star fruit within 3 days prior to first dose of venetoclax * Positive for human immunodeficiency virus (HIV) or hepatitis B or C * Receipt of a live virus vaccine within 28 days prior to Day 1 of Cycle 1 * Poor hematologic, renal, or hepatic function * Pregnant or lactating women * Life expectancy \<3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21 days) | 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. |
| FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From study start to 24 months after last dose of study drug (approximately 56 months) | 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. |
| DLBCL Cohorts: Percentage of Participants With AEs and SAEs | From study start to 3 months after last dose of study drug (approximately 21 months) | 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. |
| Number of Participants With Dose-Limiting Toxicities (DLTs) | Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase | 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. |
| RP2D of Polatuzumab Vedotin | Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase | 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. |
| RP2D of Venetoclax | Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of CT Scans Alone | 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days) | 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. |
| Percentage of Participants With Best Overall Response (BOR) of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone | 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) | 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. |
| 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) | — |
| 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) | — |
| Observed Serum Concentration of Total Antibody to 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) | Total antibody is an analyte of polatuzumab vedotin. |
| Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans | 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days) | 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. |
| Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | 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) | MMAE is an analyte of polatuzumab vedotin. |
| 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) | — |
| Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | Baseline up to approximately 2 years after last dose (up to approximately 56 months) | 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. |
| Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline up to 1 year post last dose (up to approximately 16 months) | 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. |
| Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | 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) | acMMAE is an analyte of polatuzumab vedotin. |
| Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone | 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days) | 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. |
| Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of CT Scans Alone | 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days) | 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. |
| Percentage of Participants With Objective Response (OR) at EOI, Determined by an IRC on the Basis of PET and CT Scans | 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days) | 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. |
| Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of PET and CT Scans | 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days) | 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. |
| Percentage of Participants With OR at EOI, Determined by an IRC on the Basis of CT Scans Alone | 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days) | 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. |
Countries
Australia, Italy, United States
Participant flow
Recruitment details
Participants took part in this study at 23 investigative centers in Australia, Italy, and the United States from 09 March 2016 up to 04 August 2022. The study consisted of two phases: a dose-escalation phase and a dose-expansion phase. All eligible participants in both dose-escalation and expansion phases received induction treatment, and post-induction treatment as indicated.
Pre-assignment details
A total of 133 participants with relapsed or refractory (R/R) follicular lymphoma (FL) and R/R diffuse large B-cell lymphoma (DLBCL) were enrolled in this study. Out of the 133, two participants did not receive any study treatment. Of the 131 treated participants, 74 participants with FL received Obinutuzumab (G) in combination with polatuzumab vedotin (P) and venetoclax (V) and 57 participants with DLBCL received rituximab (R) in combination with polatuzumab vedotin and venetoclax.
Participants by arm
| Arm | Count |
|---|---|
| FL Dose Escalation: 1.4P+400V+1000G Participants received venetoclax, 400 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with obinutuzumab, 1000 mg, IV infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, 1.4 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, 400 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months. | 7 |
| FL Dose Escalation: 1.4P+200V+1000G Participants received venetoclax, 200 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with obinutuzumab, 1000 mg, IV infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, 1.4 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, 200 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months. | 3 |
| FL Dose Escalation: 1.8P+400V+1000G Participants received venetoclax, 400 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with obinutuzumab, 1000 mg, IV infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, 400 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months. | 3 |
| FL Dose Escalation: 1.4P+600V+1000G Participants received venetoclax, 600 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with obinutuzumab, 1000 mg, IV infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, 1.4 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, 600 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months. | 3 |
| FL Dose Escalation: 1.8P+600V+1000G Participants received venetoclax, 600 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with obinutuzumab, 1000 mg, IV infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, 600 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months. | 9 |
| FL Dose Escalation: 1.8P+800V+1000G Participants received venetoclax, 800 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with obinutuzumab, 1000 mg, IV infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, 800 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months. | 8 |
| FL: Dose Expansion: 1.8P+800V+1000G Participants received venetoclax, 800 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with obinutuzumab, 1000 mg, IV infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, 800 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months. | 41 |
| DLBCL: Dose Escalation: 1.8P+400V+375R Participants received venetoclax, 400 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with rituximab, 375 milligrams per square meter (mg/m\^2), IV infusion, on Day 1 of Cycles 1-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR or PR at EOI received consolidation treatment until disease progression or unacceptable toxicity for up to 8 months. During consolidation treatment participants received venetoclax, 400 mg, QD, for up to 8 months and rituximab, 375 mg/m\^2 on Day 1 of every other month (1 month=28 days) starting from Month 2 up to 8 months. | 3 |
| DLBCL Dose Escalation: 1.8P+600V+375R Participants received venetoclax, 600 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with rituximab, 375 mg/m\^2, IV infusion, on Day 1 of Cycles 1-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR or PR at EOI received consolidation treatment until disease progression or unacceptable toxicity for up to 8 months. During consolidation treatment participants received venetoclax, 600 mg, QD, for up to 8 months and rituximab, 375 mg/m\^2 on Day 1 of every other month (1 month=28 days) starting from Month 2 up to 8 months. | 6 |
| DLBCL Dose Escalation: 1.8P+800V+375R Participants received venetoclax, 800 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with rituximab, 375 mg/m\^2, IV infusion, on Day 1 of Cycles 1-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR or PR at EOI received consolidation treatment until disease progression or unacceptable toxicity for up to 8 months. During consolidation treatment participants received venetoclax, 800 mg, QD, for up to 8 months and rituximab, 375 mg/m\^2 on Day 1 of every other month (1 month=28 days) starting from Month 2 up to 8 months. | 8 |
| DLBCL Dose Expansion: 1.8P+800V+375R Participants received venetoclax, 800 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with rituximab, 375 mg/m\^2, IV infusion, on Day 1 of Cycles 1-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR or PR at EOI received consolidation treatment until disease progression or unacceptable toxicity for up to 8 months. During consolidation treatment participants received venetoclax, 800 mg, QD, for up to 8 months and rituximab, 375 mg/m\^2 on Day 1 of every other month (1 month=28 days) starting from Month 2 up to 8 months. | 40 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 3 | 1 | 0 | 0 | 1 | 1 | 8 | 0 | 4 | 6 | 26 |
| Overall Study | Found Another Malignancy After Starting Trial | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 2 |
| Overall Study | Progressive Disease | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | FL Dose Escalation: 1.4P+200V+1000G | Total | DLBCL Dose Expansion: 1.8P+800V+375R | DLBCL Dose Escalation: 1.8P+800V+375R | DLBCL Dose Escalation: 1.8P+600V+375R | DLBCL: Dose Escalation: 1.8P+400V+375R | FL Dose Escalation: 1.4P+400V+1000G | FL: Dose Expansion: 1.8P+800V+1000G | FL Dose Escalation: 1.8P+800V+1000G | FL Dose Escalation: 1.8P+600V+1000G | FL Dose Escalation: 1.4P+600V+1000G | FL Dose Escalation: 1.8P+400V+1000G |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 61.3 years STANDARD_DEVIATION 8.5 | 62.8 years STANDARD_DEVIATION 11.1 | 65.8 years STANDARD_DEVIATION 9.6 | 67.4 years STANDARD_DEVIATION 15.2 | 58.7 years STANDARD_DEVIATION 17.4 | 56.0 years STANDARD_DEVIATION 16.5 | 58.9 years STANDARD_DEVIATION 6.8 | 62.2 years STANDARD_DEVIATION 11.3 | 58.0 years STANDARD_DEVIATION 11.9 | 64.6 years STANDARD_DEVIATION 6.1 | 58.3 years STANDARD_DEVIATION 10.3 | 56.7 years STANDARD_DEVIATION 13.6 |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 3 Participants | 109 Participants | 31 Participants | 7 Participants | 6 Participants | 3 Participants | 7 Participants | 30 Participants | 8 Participants | 8 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Stated | 0 Participants | 14 Participants | 6 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 5 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 4 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 15 Participants | 6 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 109 Participants | 30 Participants | 6 Participants | 6 Participants | 2 Participants | 7 Participants | 34 Participants | 7 Participants | 8 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 61 Participants | 18 Participants | 5 Participants | 4 Participants | 2 Participants | 3 Participants | 20 Participants | 4 Participants | 4 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 70 Participants | 22 Participants | 3 Participants | 2 Participants | 1 Participants | 4 Participants | 21 Participants | 4 Participants | 5 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 7 | 1 / 3 | 0 / 3 | 0 / 3 | 1 / 9 | 1 / 8 | 8 / 41 | 0 / 3 | 4 / 6 | 6 / 8 | 26 / 40 |
| other Total, other adverse events | 7 / 7 | 3 / 3 | 3 / 3 | 3 / 3 | 9 / 9 | 8 / 8 | 41 / 41 | 3 / 3 | 6 / 6 | 7 / 8 | 38 / 40 |
| serious Total, serious adverse events | 4 / 7 | 1 / 3 | 1 / 3 | 0 / 3 | 2 / 9 | 6 / 8 | 14 / 41 | 3 / 3 | 4 / 6 | 2 / 8 | 12 / 40 |
Outcome results
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.
Time frame: From study start to 3 months after last dose of study drug (approximately 21 months)
Population: Safety-evaluable population included all participants who received at least one dose of any component of the combination. The safety-evaluable population in the DLBCL cohorts were assessed in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | DLBCL Cohorts: Percentage of Participants With AEs and SAEs | AEs | 100 percentage of participants |
| FL Dose Escalation: 1.8P+800V+1000G | DLBCL Cohorts: Percentage of Participants With AEs and SAEs | SAEs | 100 percentage of participants |
| FL: Dose Expansion: 1.8P+800V+1000G | DLBCL Cohorts: Percentage of Participants With AEs and SAEs | SAEs | 66.7 percentage of participants |
| FL: Dose Expansion: 1.8P+800V+1000G | DLBCL Cohorts: Percentage of Participants With AEs and SAEs | AEs | 100 percentage of participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | DLBCL Cohorts: Percentage of Participants With AEs and SAEs | AEs | 87.5 percentage of participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | DLBCL Cohorts: Percentage of Participants With AEs and SAEs | SAEs | 25.0 percentage of participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | DLBCL Cohorts: Percentage of Participants With AEs and SAEs | AEs | 97.5 percentage of participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | DLBCL Cohorts: Percentage of Participants With AEs and SAEs | SAEs | 30.0 percentage of participants |
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.
Time frame: From study start to 24 months after last dose of study drug (approximately 56 months)
Population: Safety-evaluable population included all participants who received at least one dose of any component of the combination. The safety-evaluable population in the FL cohorts were assessed in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 100 percentage of participants |
| FL Dose Escalation: 1.8P+800V+1000G | FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 57.1 percentage of participants |
| FL: Dose Expansion: 1.8P+800V+1000G | FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 100 percentage of participants |
| FL: Dose Expansion: 1.8P+800V+1000G | FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 33.3 percentage of participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 100 percentage of participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 33.3 percentage of participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 100 percentage of participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 percentage of participants |
| FL Dose Escalation: 1.8P+600V+1000G | FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 100 percentage of participants |
| FL Dose Escalation: 1.8P+600V+1000G | FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 22.2 percentage of participants |
| FL Dose Escalation: 1.8P+800V+1000G | FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 100 percentage of participants |
| FL Dose Escalation: 1.8P+800V+1000G | FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 75.0 percentage of participants |
| FL: Dose Expansion: 1.8P+800V+1000G | FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 100 percentage of participants |
| FL: Dose Expansion: 1.8P+800V+1000G | FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 34.1 percentage of participants |
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.
Time frame: Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase
Population: Safety-evaluable population included all participants who received at least one dose of any component of the combination. The safety-evaluable population in the dose-escalation cohorts cohorts were assessed in this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | Number of Participants With Dose-Limiting Toxicities (DLTs) | 1 Participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| FL Dose Escalation: 1.8P+600V+1000G | Number of Participants With Dose-Limiting Toxicities (DLTs) | 2 Participants |
| FL Dose Escalation: 1.8P+800V+1000G | Number of Participants With Dose-Limiting Toxicities (DLTs) | 1 Participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| DLBCL Dose Escalation: 1.8P+600V+375R | Number of Participants With Dose-Limiting Toxicities (DLTs) | 1 Participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
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.
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21 days)
Population: Efficacy evaluable population included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at recommended phase 2 dose (RP2D) in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | 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 | 100 percentage of participants |
| FL: Dose Expansion: 1.8P+800V+1000G | 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 | 51.2 percentage of participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | 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 | 25 percentage of participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | 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 | 32.5 percentage of participants |
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.
Time frame: Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase
Population: Safety-evaluable population included all participants who received at least one dose of any component of the combination. The safety-evaluable population in the FL cohorts were assessed in this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | RP2D of Polatuzumab Vedotin | 1.8 mg/kg |
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.
Time frame: Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase
Population: Safety-evaluable population included all participants who received at least one dose of any component of the combination. The safety-evaluable population in the DLBCL cohorts were assessed in this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | RP2D of Venetoclax | 800 mg |
| FL: Dose Expansion: 1.8P+800V+1000G | RP2D of Venetoclax | 800 mg |
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.
Time frame: Baseline up to 1 year post last dose (up to approximately 16 months)
Population: Immunogenicity population included participants with at least one predose and one postdose HAHA or ATA assessment, with participants grouped according to histology. Number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 1 Participants |
| FL Dose Escalation: 1.8P+800V+1000G | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 1 Participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 0 Participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 0 Participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 0 Participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
| FL Dose Escalation: 1.8P+600V+1000G | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 0 Participants |
| FL Dose Escalation: 1.8P+600V+1000G | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
| FL Dose Escalation: 1.8P+800V+1000G | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
| FL Dose Escalation: 1.8P+800V+1000G | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 0 Participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 0 Participants |
| DLBCL Dose Escalation: 1.8P+600V+375R | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 0 Participants |
| DLBCL Dose Escalation: 1.8P+600V+375R | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 0 Participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 0 Participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 0 Participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
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.
Time frame: Baseline up to approximately 2 years after last dose (up to approximately 56 months)
Population: The immunogenicity population included participants with at least one predose and one postdose HAHA or ATA assessment, with participants grouped according to histology. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | Baseline prevalence of ADAs | 0 Participants |
| FL Dose Escalation: 1.8P+800V+1000G | Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | Post baseline incidence of ADAs | 0 Participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | Baseline prevalence of ADAs | 0 Participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | Post baseline incidence of ADAs | 0 Participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | Baseline prevalence of ADAs | 0 Participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | Post baseline incidence of ADAs | 0 Participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | Post baseline incidence of ADAs | 0 Participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | Baseline prevalence of ADAs | 0 Participants |
| FL Dose Escalation: 1.8P+600V+1000G | Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | Baseline prevalence of ADAs | 0 Participants |
| FL Dose Escalation: 1.8P+600V+1000G | Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | Post baseline incidence of ADAs | 0 Participants |
| FL Dose Escalation: 1.8P+800V+1000G | Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | Baseline prevalence of ADAs | 0 Participants |
| FL Dose Escalation: 1.8P+800V+1000G | Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | Post baseline incidence of ADAs | 0 Participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | Post baseline incidence of ADAs | 0 Participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab | Baseline prevalence of ADAs | 0 Participants |
Secondary
Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE)
acMMAE is an analyte of polatuzumab vedotin.
Time frame: 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)
Population: PK-evaluable population included all participants who had at least one evaluable PK sample post dose for at least one analyte. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 6 Day 1: Pre-dose | 13.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 58.5 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: 0.5 hours Post Dose | 491 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 28.1 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: 0.5 hours Post Dose | 131 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19054.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 15: Post Dose | 6.67 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 421.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: Pre-dose | 3.69 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 296.8 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: Pre-dose | NA nanograms per milliliter (ng/mL) | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 8: Post Dose | 19.1 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 890.8 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: Pre-dose | 10.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 69.4 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: 0.5 hours Post Dose | 527 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.3 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 15: Post Dose | 22.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 18.1 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: Pre-dose | 12.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 36.9 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 6 Day 1: Pre-dose | 4.62 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 5273.1 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: 0.5 hours Post Dose | 530 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 22.2 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: Pre-dose | NA nanograms per milliliter (ng/mL) | — |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: 0.5 hours Post Dose | 587 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 16.3 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: Pre-dose | 18.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 24.9 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 8: Post Dose | 57.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19.3 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: 0.5 hours Post Dose | 594 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 18.7 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: Pre-dose | NA nanograms per milliliter (ng/mL) | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: Pre-dose | 29.4 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 10.1 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: 0.5 hours Post Dose | 602 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 36.8 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: 0.5 hours Post Dose | 768 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 29.5 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 15: Post Dose | 4.56 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 5235.8 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: 0.5 hours Post Dose | 451 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 48 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: Pre-dose | 3.25 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 2446.9 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 8: Post Dose | 9.87 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 43972.4 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 6 Day 1: Pre-dose | 23.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 42.5 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: Pre-dose | 9.34 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 44.7 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: Pre-dose | 19.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 8.2 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 6 Day 1: Pre-dose | 20.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 3.7 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 15: Post Dose | 18.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 24.2 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 8: Post Dose | 49.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 33.6 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: 0.5 hours Post Dose | 555 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 3 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: 0.5 hours Post Dose | 610 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 3.4 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: Pre-dose | NA nanograms per milliliter (ng/mL) | — |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: 0.5 hours Post Dose | 620 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 7.4 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: Pre-dose | 8.27 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 62.6 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: Pre-dose | NA nanograms per milliliter (ng/mL) | — |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: 0.5 hours Post Dose | 645 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 24.6 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 8: Post Dose | 58.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 39.7 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 15: Post Dose | 17.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 56.9 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: 0.5 hours Post Dose | 682 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: Pre-dose | 23.4 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: 0.5 hours Post Dose | 553 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 90.9 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 6 Day 1: Pre-dose | 28.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: 0.5 hours Post Dose | 844 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19.7 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 8: Post Dose | 88.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 20.7 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 6 Day 1: Pre-dose | 27.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35.9 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: Pre-dose | NA nanograms per milliliter (ng/mL) | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: 0.5 hours Post Dose | 474 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 299.3 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: Pre-dose | 16.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 40.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 15: Post Dose | 31.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 15.3 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: 0.5 hours Post Dose | 825 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 20.8 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: Pre-dose | 27.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 37 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 15: Post Dose | 14.4 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 176.9 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: Pre-dose | 7.71 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 209.4 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 8: Post Dose | 41.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 192.1 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 6 Day 1: Pre-dose | 25.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 56.9 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: 0.5 hours Post Dose | 688 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 20.7 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: Pre-dose | 21.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 53.3 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: 0.5 hours Post Dose | 613 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 38.2 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: 0.5 hours Post Dose | 644 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 66.8 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: Pre-dose | NA nanograms per milliliter (ng/mL) | — |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: 0.5 hours Post Dose | 968 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 33.7 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 15: Post Dose | 26.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 69.8 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: Pre-dose | 24.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 25.8 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: 0.5 hours Post Dose | 722 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 25.3 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 8: Post Dose | 45.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.7 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: Pre-dose | NA nanograms per milliliter (ng/mL) | — |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 6 Day 1: Pre-dose | 24.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 24.4 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: Pre-dose | 14.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 66.9 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: 0.5 hours Post Dose | 749 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 23 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: Pre-dose | NA nanograms per milliliter (ng/mL) | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 6 Day 1: Pre-dose | 3.73 nanograms per milliliter (ng/mL) | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 8: Post Dose | 50.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 42.6 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: 0.5 hours Post Dose | 341 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 353.1 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: 0.5 hours Post Dose | 722 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 1.8 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: 0.5 hours Post Dose | 628 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.1 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: Pre-dose | 8.94 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 100.6 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: Pre-dose | 8.16 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 245.5 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 15: Post Dose | 19.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 50.5 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: Pre-dose | NA nanograms per milliliter (ng/mL) | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: 0.5 hours Post Dose | 748 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 17.7 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: 0.5 hours Post Dose | 683 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 22.2 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: Pre-dose | 30.1 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 12.3 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 6 Day 1: Pre-dose | 31.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 46 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 15: Post Dose | 30.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 21.5 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: 0.5 hours Post Dose | 775 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 15.2 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 8: Post Dose | 77.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 25.3 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: Pre-dose | 14.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 29.2 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: Pre-dose | 22.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49.8 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 15: Post Dose | 22.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 40.6 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: 0.5 hours Post Dose | 481 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 226.7 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: 0.5 hours Post Dose | 628 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.6 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 8: Post Dose | 57.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 42.2 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 2 Day 1: Pre-dose | 13.1 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 45.3 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 6 Day 1: Pre-dose | 24.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 54.4 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 4 Day 1: 0.5 hours Post Dose | 680 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 25.9 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) | Cycle 1 Day 1: Pre-dose | NA nanograms per milliliter (ng/mL) | — |
Secondary
Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE
MMAE is an analyte of polatuzumab vedotin.
Time frame: 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)
Population: PK-evaluable population included all participants who had at least one evaluable PK sample post dose for at least one analyte. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: 0.5 hours Post Dose | 0.152 ng/mL | Geometric Coefficient of Variation 46.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 6 Day 1: Pre-dose | 0.107 ng/mL | Geometric Coefficient of Variation 73.4 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: 0.5 hours Post Dose | 0.313 ng/mL | Geometric Coefficient of Variation 725.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 15: Post Dose | 0.225 ng/mL | Geometric Coefficient of Variation 87.4 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: Pre-dose | NA ng/mL | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.0575 ng/mL | Geometric Coefficient of Variation 117 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.131 ng/mL | Geometric Coefficient of Variation 58.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 8: Post Dose | 1.14 ng/mL | Geometric Coefficient of Variation 34.8 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: 0.5 hours Post Dose | 0.235 ng/mL | Geometric Coefficient of Variation 84.2 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: Pre-dose | NA ng/mL | — |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.103 ng/mL | Geometric Coefficient of Variation 47.1 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 6 Day 1: Pre-dose | 0.120 ng/mL | Geometric Coefficient of Variation 62.3 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: 0.5 hours Post Dose | 0.236 ng/mL | Geometric Coefficient of Variation 31.1 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: 0.5 hours Post Dose | 0.163 ng/mL | Geometric Coefficient of Variation 50.6 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 8: Post Dose | 57.5 ng/mL | Geometric Coefficient of Variation 1.46 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.106 ng/mL | Geometric Coefficient of Variation 48.3 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 15: Post Dose | 0.310 ng/mL | Geometric Coefficient of Variation 60.2 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: 0.5 hours Post Dose | 0.184 ng/mL | Geometric Coefficient of Variation 29 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: 0.5 hours Post Dose | 0.255 ng/mL | Geometric Coefficient of Variation 48.6 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: 0.5 hours Post Dose | 1.04 ng/mL | Geometric Coefficient of Variation 575.7 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: 0.5 hours Post Dose | 0.399 ng/mL | Geometric Coefficient of Variation 104.7 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.180 ng/mL | Geometric Coefficient of Variation 62.4 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.0565 ng/mL | Geometric Coefficient of Variation 132.5 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 15: Post Dose | 0.213 ng/mL | Geometric Coefficient of Variation 174.3 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 8: Post Dose | 1.57 ng/mL | Geometric Coefficient of Variation 63.6 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 6 Day 1: Pre-dose | 0.0715 ng/mL | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: Pre-dose | NA ng/mL | — |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: 0.5 hours Post Dose | 0.270 ng/mL | Geometric Coefficient of Variation 31.6 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: 0.5 hours Post Dose | 0.175 ng/mL | Geometric Coefficient of Variation 57 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 6 Day 1: Pre-dose | 0.239 ng/mL | Geometric Coefficient of Variation 17.2 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 8: Post Dose | 1.06 ng/mL | Geometric Coefficient of Variation 43.6 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: Pre-dose | NA ng/mL | — |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.172 ng/mL | Geometric Coefficient of Variation 46.8 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.0982 ng/mL | Geometric Coefficient of Variation 75.3 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 15: Post Dose | 0.341 ng/mL | Geometric Coefficient of Variation 55.9 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: 0.5 hours Post Dose | 0.417 ng/mL | Geometric Coefficient of Variation 60.3 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 8: Post Dose | 1.66 ng/mL | Geometric Coefficient of Variation 69.9 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 15: Post Dose | 0.461 ng/mL | Geometric Coefficient of Variation 76.6 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: Pre-dose | NA ng/mL | — |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: 0.5 hours Post Dose | 0.231 ng/mL | Geometric Coefficient of Variation 76.5 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.155 ng/mL | Geometric Coefficient of Variation 46.5 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: 0.5 hours Post Dose | 0.209 ng/mL | Geometric Coefficient of Variation 42 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.0866 ng/mL | Geometric Coefficient of Variation 141.8 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: 0.5 hours Post Dose | 0.507 ng/mL | Geometric Coefficient of Variation 112 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 6 Day 1: Pre-dose | 0.189 ng/mL | Geometric Coefficient of Variation 37.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.688 ng/mL | Geometric Coefficient of Variation 73.8 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: Pre-dose | NA ng/mL | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: 0.5 hours Post Dose | NA ng/mL | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 8: Post Dose | 0.323 ng/mL | Geometric Coefficient of Variation 79.3 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 15: Post Dose | 2.26 ng/mL | Geometric Coefficient of Variation 76.3 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: 0.5 hours Post Dose | 0.150 ng/mL | Geometric Coefficient of Variation 41.9 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.263 ng/mL | Geometric Coefficient of Variation 46.5 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: 0.5 hours Post Dose | 0.206 ng/mL | Geometric Coefficient of Variation 36.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 6 Day 1: Pre-dose | 0.289 ng/mL | Geometric Coefficient of Variation 55.2 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.167 ng/mL | Geometric Coefficient of Variation 81 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: 0.5 hours Post Dose | 0.441 ng/mL | Geometric Coefficient of Variation 208.3 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.113 ng/mL | Geometric Coefficient of Variation 136.1 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 6 Day 1: Pre-dose | 0.162 ng/mL | Geometric Coefficient of Variation 94.9 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 8: Post Dose | 1.81 ng/mL | Geometric Coefficient of Variation 65.3 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: 0.5 hours Post Dose | 0.260 ng/mL | Geometric Coefficient of Variation 56.2 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: Pre-dose | NA ng/mL | — |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: 0.5 hours Post Dose | 0.257 ng/mL | Geometric Coefficient of Variation 63.8 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 15: Post Dose | 0.444 ng/mL | Geometric Coefficient of Variation 99.8 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: 0.5 hours Post Dose | 0.249 ng/mL | Geometric Coefficient of Variation 8.7 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: 0.5 hours Post Dose | 0.331 ng/mL | Geometric Coefficient of Variation 77.4 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 6 Day 1: Pre-dose | 0.197 ng/mL | Geometric Coefficient of Variation 275.2 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: 0.5 hours Post Dose | 0.343 ng/mL | Geometric Coefficient of Variation 122 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.221 ng/mL | Geometric Coefficient of Variation 199.1 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 8: Post Dose | 2.34 ng/mL | Geometric Coefficient of Variation 54.7 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.238 ng/mL | Geometric Coefficient of Variation 75.5 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: Pre-dose | NA ng/mL | — |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 15: Post Dose | 0.675 ng/mL | Geometric Coefficient of Variation 144.7 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: 0.5 hours Post Dose | 0.564 ng/mL | Geometric Coefficient of Variation 76.4 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: 0.5 hours Post Dose | 0.565 ng/mL | Geometric Coefficient of Variation 107.5 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.459 ng/mL | Geometric Coefficient of Variation 103.4 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 15: Post Dose | 0.927 ng/mL | Geometric Coefficient of Variation 89.8 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: Pre-dose | NA ng/mL | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 8: Post Dose | 2.77 ng/mL | Geometric Coefficient of Variation 63.1 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: 0.5 hours Post Dose | 0.390 ng/mL | Geometric Coefficient of Variation 89 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.311 ng/mL | Geometric Coefficient of Variation 76.4 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 6 Day 1: Pre-dose | 0.795 ng/mL | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: 0.5 hours Post Dose | 0.407 ng/mL | Geometric Coefficient of Variation 116.2 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 15: Post Dose | 0.778 ng/mL | Geometric Coefficient of Variation 77.9 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 8: Post Dose | 2.51 ng/mL | Geometric Coefficient of Variation 96.3 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.295 ng/mL | Geometric Coefficient of Variation 90.5 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: 0.5 hours Post Dose | 0.262 ng/mL | Geometric Coefficient of Variation 61.9 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 6 Day 1: Pre-dose | 0.334 ng/mL | Geometric Coefficient of Variation 62.1 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: 0.5 hours Post Dose | 0.364 ng/mL | Geometric Coefficient of Variation 65.6 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: Pre-dose | NA ng/mL | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.266 ng/mL | Geometric Coefficient of Variation 161.7 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: 0.5 hours Post Dose | 0.311 ng/mL | Geometric Coefficient of Variation 57.7 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: 0.5 hours Post Dose | 0.263 ng/mL | Geometric Coefficient of Variation 90.8 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.220 ng/mL | Geometric Coefficient of Variation 72.7 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 6 Day 1: Pre-dose | 0.211 ng/mL | Geometric Coefficient of Variation 93.8 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 8: Post Dose | 2.51 ng/mL | Geometric Coefficient of Variation 65.1 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: 0.5 hours Post Dose | 0.322 ng/mL | Geometric Coefficient of Variation 55.9 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.227 ng/mL | Geometric Coefficient of Variation 66.1 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 1: Pre-dose | NA ng/mL | — |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE | Cycle 1 Day 15: Post Dose | 0.723 ng/mL | Geometric Coefficient of Variation 63.3 |
Secondary
Observed Plasma Venetoclax Concentration
Time frame: 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)
Population: PK-evaluable population included all participants who had at least one evaluable PK sample post dose for at least one analyte. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 6 hours Post Dose | 1.38 µg/mL | Geometric Coefficient of Variation 83.4 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: Pre-dose | 0.336 µg/mL | Geometric Coefficient of Variation 99.3 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 1 Day 1: Post Dose | 0.624 µg/mL | Geometric Coefficient of Variation 94.6 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 2 hours Post Dose | 0.532 µg/mL | Geometric Coefficient of Variation 119.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 8 hours Post Dose | 1.40 µg/mL | Geometric Coefficient of Variation 74.9 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 4 Day 1: Pre-dose | 0.259 µg/mL | Geometric Coefficient of Variation 157.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 4 hours Post Dose | 1.12 µg/mL | Geometric Coefficient of Variation 102.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 6 Day 1: Pre-dose | 0.252 µg/mL | Geometric Coefficient of Variation 95 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 4 Day 1: Pre-dose | 0.0344 µg/mL | Geometric Coefficient of Variation 15072.4 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 2 hours Post Dose | 0.306 µg/mL | Geometric Coefficient of Variation 107.3 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 6 Day 1: Pre-dose | 0.277 µg/mL | Geometric Coefficient of Variation 178.7 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 1 Day 1: Post Dose | 0.247 µg/mL | Geometric Coefficient of Variation 162.1 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 8 hours Post Dose | 0.803 µg/mL | Geometric Coefficient of Variation 76.7 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 6 hours Post Dose | 0.933 µg/mL | Geometric Coefficient of Variation 72.1 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: Pre-dose | 0.347 µg/mL | Geometric Coefficient of Variation 144.3 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 4 hours Post Dose | 0.572 µg/mL | Geometric Coefficient of Variation 49.1 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 2 hours Post Dose | 0.351 µg/mL | Geometric Coefficient of Variation 129.3 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 4 Day 1: Pre-dose | 0.302 µg/mL | Geometric Coefficient of Variation 1.2 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: Pre-dose | 0.453 µg/mL | Geometric Coefficient of Variation 71.9 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 1 Day 1: Post Dose | 0.108 µg/mL | Geometric Coefficient of Variation 53.3 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 4 hours Post Dose | 0.548 µg/mL | Geometric Coefficient of Variation 51 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 6 Day 1: Pre-dose | 0.0177 µg/mL | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 8 hours Post Dose | 1.45 µg/mL | Geometric Coefficient of Variation 32.3 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 6 hours Post Dose | 1.21 µg/mL | Geometric Coefficient of Variation 24.8 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 1 Day 1: Post Dose | 0.244 µg/mL | Geometric Coefficient of Variation 149.1 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 4 Day 1: Pre-dose | 1.12 µg/mL | Geometric Coefficient of Variation 40.2 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: Pre-dose | 0.943 µg/mL | Geometric Coefficient of Variation 28.5 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 2 hours Post Dose | 0.822 µg/mL | Geometric Coefficient of Variation 54.8 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 4 hours Post Dose | 1.31 µg/mL | Geometric Coefficient of Variation 22.5 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 6 Day 1: Pre-dose | 1.24 µg/mL | Geometric Coefficient of Variation 56.1 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 6 hours Post Dose | 1.99 µg/mL | Geometric Coefficient of Variation 5.7 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 8 hours Post Dose | 2.24 µg/mL | Geometric Coefficient of Variation 18.4 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 4 hours Post Dose | 1.65 µg/mL | Geometric Coefficient of Variation 69.4 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 6 hours Post Dose | 2.15 µg/mL | Geometric Coefficient of Variation 51.9 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 2 hours Post Dose | 0.769 µg/mL | Geometric Coefficient of Variation 131 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Venetoclax Concentration | Cycle 4 Day 1: Pre-dose | 0.551 µg/mL | Geometric Coefficient of Variation 98.4 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Venetoclax Concentration | Cycle 1 Day 1: Post Dose | 0.796 µg/mL | Geometric Coefficient of Variation 86.5 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: Pre-dose | 0.298 µg/mL | Geometric Coefficient of Variation 2853.1 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Venetoclax Concentration | Cycle 6 Day 1: Pre-dose | 0.595 µg/mL | Geometric Coefficient of Variation 95.4 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 8 hours Post Dose | 2.46 µg/mL | Geometric Coefficient of Variation 59.8 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: Pre-dose | 0.282 µg/mL | Geometric Coefficient of Variation 498.3 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 4 Day 1: Pre-dose | 0.304 µg/mL | Geometric Coefficient of Variation 1059.7 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 6 hours Post Dose | 2.55 µg/mL | Geometric Coefficient of Variation 28 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 8 hours Post Dose | 2.53 µg/mL | Geometric Coefficient of Variation 32.7 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 2 hours Post Dose | 0.921 µg/mL | Geometric Coefficient of Variation 74 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 4 hours Post Dose | 2.04 µg/mL | Geometric Coefficient of Variation 39.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 1 Day 1: Post Dose | 0.811 µg/mL | Geometric Coefficient of Variation 310.3 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 6 Day 1: Pre-dose | 0.0266 µg/mL | Geometric Coefficient of Variation 26843.8 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 2 hours Post Dose | 2.69 µg/mL | — |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: Pre-dose | 0.555 µg/mL | Geometric Coefficient of Variation 1134.4 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 4 hours Post Dose | 1.99 µg/mL | Geometric Coefficient of Variation 59 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 4 Day 1: Pre-dose | 0.561 µg/mL | Geometric Coefficient of Variation 401.2 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 6 Day 1: Pre-dose | 0.509 µg/mL | Geometric Coefficient of Variation 496.6 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 6 hours Post Dose | 4.82 µg/mL | — |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 1 Day 1: Post Dose | 0.964 µg/mL | Geometric Coefficient of Variation 69.2 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 8 hours Post Dose | 3.02 µg/mL | — |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 2 hours Post Dose | 0.632 µg/mL | Geometric Coefficient of Variation 90.1 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 8 hours Post Dose | 0.886 µg/mL | Geometric Coefficient of Variation 87.6 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Venetoclax Concentration | Cycle 6 Day 1: Pre-dose | 0.175 µg/mL | Geometric Coefficient of Variation 187.9 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Venetoclax Concentration | Cycle 1 Day 1: Post Dose | 0.503 µg/mL | Geometric Coefficient of Variation 47.9 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 4 hours Post Dose | 0.830 µg/mL | Geometric Coefficient of Variation 75.3 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Venetoclax Concentration | Cycle 4 Day 1: Pre-dose | 0.0581 µg/mL | Geometric Coefficient of Variation 1105.7 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 6 hours Post Dose | 0.870 µg/mL | Geometric Coefficient of Variation 98.1 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: Pre-dose | 0.529 µg/mL | Geometric Coefficient of Variation 135.6 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 6 hours Post Dose | 1.96 µg/mL | Geometric Coefficient of Variation 57.5 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 2 hours Post Dose | 1.08 µg/mL | Geometric Coefficient of Variation 82 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 4 hours Post Dose | 1.49 µg/mL | Geometric Coefficient of Variation 43.1 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 8 hours Post Dose | 1.88 µg/mL | Geometric Coefficient of Variation 70.8 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: Pre-dose | 0.952 µg/mL | Geometric Coefficient of Variation 139.7 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 4 Day 1: Pre-dose | 0.933 µg/mL | Geometric Coefficient of Variation 74.2 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 6 Day 1: Pre-dose | 1.90 µg/mL | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 1 Day 1: Post Dose | 0.915 µg/mL | Geometric Coefficient of Variation 47.4 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 4 Day 1: Pre-dose | 0.826 µg/mL | Geometric Coefficient of Variation 311.3 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 6 Day 1: Pre-dose | 0.0772 µg/mL | Geometric Coefficient of Variation 101668.3 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 1 Day 1: Post Dose | 1.21 µg/mL | Geometric Coefficient of Variation 103.4 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: Pre-dose | 0.852 µg/mL | Geometric Coefficient of Variation 1812.3 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 2 hours Post Dose | 1.01 µg/mL | Geometric Coefficient of Variation 464.7 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 4 hours Post Dose | 2.03 µg/mL | Geometric Coefficient of Variation 131.4 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 6 hours Post Dose | 2.74 µg/mL | Geometric Coefficient of Variation 117.9 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 8 hours Post Dose | 2.85 µg/mL | Geometric Coefficient of Variation 94.7 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 4 Day 1: Post Dose | 1.04 µg/mL | Geometric Coefficient of Variation 8.4 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 4 Day 1: Pre-dose | 0.337 µg/mL | Geometric Coefficient of Variation 1043.6 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 8 hours Post Dose | 6.66 µg/mL | — |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 6 hours Post Dose | 5.95 µg/mL | — |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 4 hours Post Dose | 1.50 µg/mL | Geometric Coefficient of Variation 74.5 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: 2 hours Post Dose | NA µg/mL | Geometric Coefficient of Variation 5.13 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 2 Day 1: Pre-dose | 0.329 µg/mL | Geometric Coefficient of Variation 1047.7 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 1 Day 1: Post Dose | 0.841 µg/mL | Geometric Coefficient of Variation 94.8 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 1 Day 1: Pre-dose | NA µg/mL | — |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Plasma Venetoclax Concentration | Cycle 6 Day 1: Pre-dose | 0.365 µg/mL | Geometric Coefficient of Variation 780.9 |
Secondary
Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin
Total antibody is an analyte of polatuzumab vedotin.
Time frame: 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)
Population: PK-evaluable population included all participants who had at least one evaluable PK sample post dose for at least one analyte. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 4 Day 1: Pre-dose | 2.73 µg/mL | Geometric Coefficient of Variation 76.1 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | One Year Post Last Dose | 0.0250 µg/mL | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 1 Day 1: Pre-dose | NA µg/mL | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 2 Day 1: Pre-dose | 0.798 µg/mL | Geometric Coefficient of Variation 404.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Day 120 Post Last Dose | 0.0250 µg/mL | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Study Drug Discontinuation Visit | 0.0250 µg/mL | — |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 4 Day 1: Pre-dose | 6.12 µg/mL | Geometric Coefficient of Variation 26.1 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Study Drug Discontinuation Visit | 0.0250 µg/mL | — |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 1 Day 1: Pre-dose | NA µg/mL | — |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 2 Day 1: Pre-dose | 3.14 µg/mL | Geometric Coefficient of Variation 29.4 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Day 120 Post Last Dose | 0.0250 µg/mL | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | One Year Post Last Dose | 0.0250 µg/mL | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 1 Day 1: Pre-dose | NA µg/mL | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 4 Day 1: Pre-dose | 7.88 µg/mL | Geometric Coefficient of Variation 9.5 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Day 120 Post Last Dose | 0.0906 µg/mL | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 2 Day 1: Pre-dose | 0.677 µg/mL | Geometric Coefficient of Variation 6220.9 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Study Drug Discontinuation Visit | 0.0534 µg/mL | — |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | One Year Post Last Dose | 0.0250 µg/mL | — |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Study Drug Discontinuation Visit | 0.0250 µg/mL | — |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Day 120 Post Last Dose | 0.0250 µg/mL | — |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 2 Day 1: Pre-dose | 2.03 µg/mL | Geometric Coefficient of Variation 46.4 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 4 Day 1: Pre-dose | 5.40 µg/mL | Geometric Coefficient of Variation 18.4 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 1 Day 1: Pre-dose | NA µg/mL | — |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Day 120 Post Last Dose | 0.0832 µg/mL | — |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 1 Day 1: Pre-dose | NA µg/mL | — |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 2 Day 1: Pre-dose | 1.75 µg/mL | Geometric Coefficient of Variation 63.2 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 4 Day 1: Pre-dose | 5.72 µg/mL | Geometric Coefficient of Variation 33.5 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Study Drug Discontinuation Visit | 0.0250 µg/mL | — |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | One Year Post Last Dose | 0.0250 µg/mL | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Day 120 Post Last Dose | 0.156 µg/mL | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 2 Day 1: Pre-dose | 4.22 µg/mL | Geometric Coefficient of Variation 31.1 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | One Year Post Last Dose | 0.0250 µg/mL | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 1 Day 1: Pre-dose | NA µg/mL | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Study Drug Discontinuation Visit | 0.0900 µg/mL | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 4 Day 1: Pre-dose | 8.19 µg/mL | Geometric Coefficient of Variation 32.3 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 1 Day 1: Pre-dose | NA µg/mL | — |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 4 Day 1: Pre-dose | 5.88 µg/mL | Geometric Coefficient of Variation 63.7 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 2 Day 1: Pre-dose | 1.73 µg/mL | Geometric Coefficient of Variation 265.3 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | One Year Post Last Dose | 0.0294 µg/mL | — |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Day 120 Post Last Dose | 0.494 µg/mL | Geometric Coefficient of Variation 468.8 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Study Drug Discontinuation Visit | 0.110 µg/mL | — |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 4 Day 1: Pre-dose | 6.84 µg/mL | Geometric Coefficient of Variation 29.5 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 2 Day 1: Pre-dose | 3.34 µg/mL | Geometric Coefficient of Variation 56.6 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Study Drug Discontinuation Visit | 2.43 µg/mL | — |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Day 120 Post Last Dose | 0.385 µg/mL | Geometric Coefficient of Variation 28.6 |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 1 Day 1: Pre-dose | NA µg/mL | — |
| DLBCL Dose Escalation: 1.8P+600V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | One Year Post Last Dose | 0.0250 µg/mL | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 1 Day 1: Pre-dose | NA µg/mL | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 2 Day 1: Pre-dose | 2.23 µg/mL | Geometric Coefficient of Variation 83.5 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Study Drug Discontinuation Visit | 4.71 µg/mL | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | One Year Post Last Dose | 0.0250 µg/mL | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 4 Day 1: Pre-dose | 2.34 µg/mL | Geometric Coefficient of Variation 82.1 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 1 Day 1: Pre-dose | NA µg/mL | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Day 120 Post Last Dose | 0.759 µg/mL | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 4 Day 1: Pre-dose | 8.22 µg/mL | Geometric Coefficient of Variation 17 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 2 Day 1: Pre-dose | 3.41 µg/mL | Geometric Coefficient of Variation 30.9 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Study Drug Discontinuation Visit | 1.38 µg/mL | Geometric Coefficient of Variation 203 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | One Year Post Last Dose | 0.0457 µg/mL | — |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 2 Day 1: Pre-dose | 3.04 µg/mL | Geometric Coefficient of Variation 70.8 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 4 Day 1: Pre-dose | 5.82 µg/mL | Geometric Coefficient of Variation 45.7 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Study Drug Discontinuation Visit | 1.03 µg/mL | Geometric Coefficient of Variation 471.1 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Day 120 Post Last Dose | 1.37 µg/mL | Geometric Coefficient of Variation 93.2 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin | Cycle 1 Day 1: Pre-dose | NA µg/mL | — |
Secondary
Observed Serum Obinutuzumab Concentration
Time frame: 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)
Population: Pharmacokinetics (PK) evaluable population included all participants who had at least one evaluable PK sample post dose for at least one analyte. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | One Year Post Last Dose | 0.0410 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 20351.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 20 | 242 micrograms per milliliter (µg/mL) | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 6 Day 1: Pre-dose | 288 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 62.9 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Study Drug Discontinuation Visit | 9.61 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 438943.9 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 1 Day 1: Pre-dose | NA micrograms per milliliter (µg/mL) | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 6 Day 1: 0.5 hours Post Dose | 582 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 26.8 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 2 Day 1: 0.5 hours Post Dose | 637 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 32 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 1 Day 1: 0.5 hours Post Dose | 310 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 21.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 8 | 148 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 161.8 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 4 Day 1: 0.5 hours Post Dose | 534 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 62.9 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 14 | 189 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 112.9 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Day 120 Post Last Dose | 39.9 micrograms per milliliter (µg/mL) | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 4 Day 1: Pre-dose | 284 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 50.9 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 2 | 117 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 471.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 2 Day 1: Pre-dose | 327 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 46.7 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 6 Day 1: Pre-dose | 582 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 26.5 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 6 Day 1: 0.5 hours Post Dose | 887 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 19.6 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 1 Day 1: 0.5 hours Post Dose | 360 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 18.8 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Study Drug Discontinuation Visit | 134 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 1414.6 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 2 Day 1: Pre-dose | 498 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 20.6 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 1 Day 1: Pre-dose | NA micrograms per milliliter (µg/mL) | — |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 20 | 218 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 30.7 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 2 Day 1: 0.5 hours Post Dose | 822 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 17 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 14 | 226 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 28.9 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 4 Day 1: Pre-dose | 496 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 25.3 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 8 | 184 micrograms per milliliter (µg/mL) | — |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 4 Day 1: 0.5 hours Post Dose | 842 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 25.1 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 2 | 294 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 53.3 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Study Drug Discontinuation Visit | 4.48 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 2973890.2 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Day 120 Post Last Dose | 1.72 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 1634893.3 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Cycle 4 Day 1: Pre-dose | 376 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 9.6 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | One Year Post Last Dose | 0.0585 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 372.7 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Cycle 1 Day 1: Pre-dose | NA micrograms per milliliter (µg/mL) | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Maintenance Month 8 | 191 micrograms per milliliter (µg/mL) | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Maintenance Month 2 | 205 micrograms per milliliter (µg/mL) | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Cycle 1 Day 1: 0.5 hours Post Dose | 169 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 60.2 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Cycle 6 Day 1: Pre-dose | 338 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 4 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Cycle 4 Day 1: 0.5 hours Post Dose | 709 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 20.1 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Cycle 2 Day 1: 0.5 hours Post Dose | 512 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 56.1 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Maintenance Month 20 | 74.0 micrograms per milliliter (µg/mL) | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Cycle 2 Day 1: Pre-dose | 288 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 43.2 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Maintenance Month 14 | 197 micrograms per milliliter (µg/mL) | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Cycle 6 Day 1: 0.5 hours Post Dose | 490 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 65.2 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Cycle 2 Day 1: 0.5 hours Post Dose | 685 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 17.8 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Cycle 1 Day 1: Pre-dose | NA micrograms per milliliter (µg/mL) | — |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Cycle 1 Day 1: 0.5 hours Post Dose | 342 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 11 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Cycle 2 Day 1: Pre-dose | 395 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 17 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Cycle 4 Day 1: Pre-dose | 337 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 12 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Cycle 4 Day 1: 0.5 hours Post Dose | 732 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 13.4 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Cycle 6 Day 1: Pre-dose | 335 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 10.2 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Cycle 6 Day 1: 0.5 hours Post Dose | 659 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 14.3 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Maintenance Month 2 | 192 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 11.7 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Maintenance Month 8 | 114 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 30 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Maintenance Month 14 | 138 micrograms per milliliter (µg/mL) | — |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Study Drug Discontinuation Visit | 66.6 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 271 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | Day 120 Post Last Dose | 0.660 micrograms per milliliter (µg/mL) | — |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Obinutuzumab Concentration | One Year Post Last Dose | 0.00680 micrograms per milliliter (µg/mL) | — |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 4 Day 1: 0.5 hours Post Dose | 819 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 18.6 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Obinutuzumab Concentration | Study Drug Discontinuation Visit | 262 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 11.9 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 14 | 133 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 23.5 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 6 Day 1: 0.5 hours Post Dose | 857 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 21.2 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Obinutuzumab Concentration | One Year Post Last Dose | 0.244 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 716.1 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 2 Day 1: 0.5 hours Post Dose | 800 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 19.1 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 2 Day 1: Pre-dose | 435 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 25.4 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 2 | 273 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 63.4 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 20 | 156 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 44.2 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 1 Day 1: Pre-dose | NA micrograms per milliliter (µg/mL) | — |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 8 | 170 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 40.2 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 6 Day 1: Pre-dose | 437 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 24.5 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Obinutuzumab Concentration | Day 120 Post Last Dose | 41.2 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 89.5 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 4 Day 1: Pre-dose | 422 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 20.3 |
| FL Dose Escalation: 1.8P+600V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 1 Day 1: 0.5 hours Post Dose | 262 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 106 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 6 Day 1: Pre-dose | 420 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 44.5 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 4 Day 1: 0.5 hours Post Dose | 925 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 26.9 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 1 Day 1: Pre-dose | NA micrograms per milliliter (µg/mL) | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 2 | 327 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 57.6 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 4 Day 1: Pre-dose | 454 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 37.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 8 | 210 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 27 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 2 Day 1: 0.5 hours Post Dose | 975 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 19.3 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 14 | 190 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 17.9 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 2 Day 1: Pre-dose | 497 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 20.3 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 20 | 144 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 26.9 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 1 Day 1: 0.5 hours Post Dose | 438 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 17.8 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Study Drug Discontinuation Visit | 212 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 34.8 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | One Year Post Last Dose | 0.0820 micrograms per milliliter (µg/mL) | — |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Day 120 Post Last Dose | 94.6 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 85.6 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 6 Day 1: 0.5 hours Post Dose | 841 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 28.1 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | One Year Post Last Dose | 4.89 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 9002.8 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 4 Day 1: Pre-dose | 397 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 40.5 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Study Drug Discontinuation Visit | 148 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 110.1 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 2 Day 1: 0.5 hours Post Dose | 834 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 30.3 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 1 Day 1: Pre-dose | NA micrograms per milliliter (µg/mL) | — |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 2 | 291 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 60.8 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 8 | 168 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 72 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 6 Day 1: 0.5 hours Post Dose | 807 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 27 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 6 Day 1: Pre-dose | 428 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 51.9 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 4 Day 1: 0.5 hours Post Dose | 770 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 25.6 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 20 | 180 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 62 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 2 Day 1: Pre-dose | 422 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 29 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Cycle 1 Day 1: 0.5 hours Post Dose | 261 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 115.1 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Day 120 Post Last Dose | 44.1 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 274.2 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Obinutuzumab Concentration | Maintenance Month 14 | 168 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 41.3 |
Secondary
Observed Serum Rituximab Concentration
Time frame: 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)
Population: PK-evaluable population included all participants who had at least one evaluable PK sample post dose for at least one analyte. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Rituximab Concentration | Cycle 6 Day 1: Pre-dose | 120 µg/mL | Geometric Coefficient of Variation 8.8 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Rituximab Concentration | Cycle 1 Day 1: 0.5 hours Post Dose | 199 µg/mL | Geometric Coefficient of Variation 25.4 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Rituximab Concentration | Cycle 6 Day 1: 0.5 hours Post Dose | 303 µg/mL | Geometric Coefficient of Variation 12.4 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Rituximab Concentration | Cycle 2 Day 1: Pre-dose | 49.3 µg/mL | Geometric Coefficient of Variation 17.2 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Rituximab Concentration | Cycle 4 Day 1:Pre-dose | 88.9 µg/mL | Geometric Coefficient of Variation 11.1 |
| FL Dose Escalation: 1.8P+800V+1000G | Observed Serum Rituximab Concentration | Cycle 1 Day 1: Pre-dose | NA µg/mL | — |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Rituximab Concentration | Cycle 2 Day 1: Pre-dose | 38.9 µg/mL | Geometric Coefficient of Variation 61.7 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Rituximab Concentration | Cycle 6 Day 1: Pre-dose | 20.9 µg/mL | — |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Rituximab Concentration | Cycle 4 Day 1:Pre-dose | 39.3 µg/mL | Geometric Coefficient of Variation 71 |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Rituximab Concentration | Cycle 6 Day 1: 0.5 hours Post Dose | 182 µg/mL | — |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Rituximab Concentration | Cycle 1 Day 1: Pre-dose | NA µg/mL | — |
| FL: Dose Expansion: 1.8P+800V+1000G | Observed Serum Rituximab Concentration | Cycle 1 Day 1: 0.5 hours Post Dose | 189 µg/mL | Geometric Coefficient of Variation 6.8 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Rituximab Concentration | Cycle 6 Day 1: Pre-dose | 151 µg/mL | Geometric Coefficient of Variation 32.4 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Rituximab Concentration | Cycle 1 Day 1: 0.5 hours Post Dose | 255 µg/mL | Geometric Coefficient of Variation 14 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Rituximab Concentration | Cycle 4 Day 1:Pre-dose | 126 µg/mL | Geometric Coefficient of Variation 16.5 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Rituximab Concentration | Cycle 2 Day 1: Pre-dose | 71.0 µg/mL | Geometric Coefficient of Variation 42.1 |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Rituximab Concentration | Cycle 1 Day 1: Pre-dose | NA µg/mL | — |
| DLBCL Dose Escalation: 1.8P+800V+375R | Observed Serum Rituximab Concentration | Cycle 6 Day 1: 0.5 hours Post Dose | 229 µg/mL | Geometric Coefficient of Variation 36.9 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Rituximab Concentration | Cycle 6 Day 1: 0.5 hours Post Dose | 308 µg/mL | Geometric Coefficient of Variation 27.2 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Rituximab Concentration | Cycle 1 Day 1: Pre-dose | NA µg/mL | — |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Rituximab Concentration | Cycle 1 Day 1: 0.5 hours Post Dose | 146 µg/mL | Geometric Coefficient of Variation 159.3 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Rituximab Concentration | Cycle 2 Day 1: Pre-dose | 50.1 µg/mL | Geometric Coefficient of Variation 30.5 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Rituximab Concentration | Cycle 4 Day 1:Pre-dose | 88.1 µg/mL | Geometric Coefficient of Variation 43.4 |
| DLBCL Dose Expansion: 1.8P+800V+375R | Observed Serum Rituximab Concentration | Cycle 6 Day 1: Pre-dose | 117 µg/mL | Geometric Coefficient of Variation 43.4 |
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.
Time frame: 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)
Population: Efficacy evaluable population included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | Percentage of Participants With Best Overall Response (BOR) of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone | 100.0 percentage of participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Percentage of Participants With Best Overall Response (BOR) of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone | 87.8 percentage of participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Percentage of Participants With Best Overall Response (BOR) of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone | 50.0 percentage of participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | Percentage of Participants With Best Overall Response (BOR) of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone | 72.5 percentage of participants |
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.
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Population: Efficacy evaluable population included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of CT Scans Alone | 75.0 percentage of participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of CT Scans Alone | 29.3 percentage of participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of CT Scans Alone | 25.0 percentage of participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of CT Scans Alone | 22.5 percentage of participants |
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.
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Population: Efficacy evaluable population included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans | 100 percentage of participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans | 51.2 percentage of participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans | 25.0 percentage of participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans | 32.5 percentage of participants |
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.
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Population: Efficacy evaluable population included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone | 62.5 percentage of participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone | 36.6 percentage of participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone | 16.7 percentage of participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone | 26.5 percentage of participants |
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.
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Population: Efficacy evaluable population included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | Percentage of Participants With Objective Response (OR) at EOI, Determined by an IRC on the Basis of PET and CT Scans | 100.0 percentage of participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Percentage of Participants With Objective Response (OR) at EOI, Determined by an IRC on the Basis of PET and CT Scans | 70.7 percentage of participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Percentage of Participants With Objective Response (OR) at EOI, Determined by an IRC on the Basis of PET and CT Scans | 25.0 percentage of participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | Percentage of Participants With Objective Response (OR) at EOI, Determined by an IRC on the Basis of PET and CT Scans | 37.5 percentage of participants |
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.
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Population: Efficacy evaluable population included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | Percentage of Participants With OR at EOI, Determined by an IRC on the Basis of CT Scans Alone | 87.5 percentage of participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Percentage of Participants With OR at EOI, Determined by an IRC on the Basis of CT Scans Alone | 82.9 percentage of participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Percentage of Participants With OR at EOI, Determined by an IRC on the Basis of CT Scans Alone | 25.0 percentage of participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | Percentage of Participants With OR at EOI, Determined by an IRC on the Basis of CT Scans Alone | 37.5 percentage of participants |
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.
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Population: Efficacy evaluable population included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of CT Scans Alone | 87.5 percentage of participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of CT Scans Alone | 85.4 percentage of participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of CT Scans Alone | 37.5 percentage of participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of CT Scans Alone | 45.0 percentage of participants |
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.
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Population: Efficacy evaluable population included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FL Dose Escalation: 1.8P+800V+1000G | Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of PET and CT Scans | 100.0 percentage of participants |
| FL: Dose Expansion: 1.8P+800V+1000G | Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of PET and CT Scans | 75.6 percentage of participants |
| DLBCL Dose Escalation: 1.8P+800V+375R | Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of PET and CT Scans | 37.5 percentage of participants |
| DLBCL Dose Expansion: 1.8P+800V+375R | Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of PET and CT Scans | 42.5 percentage of participants |