A Study Evaluating the Safety, Efficacy and Pharmacokinetics of Venetoclax Combined With Chemotherapy in Participants With B-Cell Non-Hodgkin's Lymphoma (NHL) and DLBCL

CR was defined as follows according to modified Lugano classification for PET/CT-based response: Lymph nodes and extra-lymphatic sites with score 1, 2, or 3 with or without a residual mass on 5-point scale with 1) no uptake above background; 2) uptake \</= mediastinum; 3) uptake \< mediastinum but \</= liver. No evidence of fluorodeoxyglucose (FDG)-uptake disease in marrow. If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy.

Time frame: Baseline up to end of treatment (up to approximately 6 months)

Population: Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for subgroup of the ITT, DE Participants.

CR was defined as follows according to modified Lugano classification for PET/CT-based response: Lymph nodes and extra-lymphatic sites with score 1, 2, or 3 with or without a residual mass on 5-point scale with 1) no uptake above background; 2) uptake \</= mediastinum; 3) uptake \< mediastinum but \</= liver. No evidence of fluorodeoxyglucose (FDG)-uptake disease in marrow. If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy

Time frame: Baseline up to end of treatment (up to approximately 6 months)

Population: Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available.

DLTs were reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0). Decrease in B cells, lymphopenia, and leukopenia caused by lymphopenia were not considered DLTs but instead were expected outcomes of study treatment. Any Grade \>/= 3 adverse event, that was attributed to having a reasonable possibility of being related to the combined administration of venetoclax plus R-CHOP or G-CHOP, that could not be attributed by the investigator to an alternative, clearly identifiable cause such as tumor progression, concurrent illness or medical condition, or concomitant medication and that occurred during the DLT observation period (start of venetoclax treatment through end of Cycle 2) was considered a DLT for dose-escalation purposes. Grade 3 or 4 neutropenia or thrombocytopenia identified on Day 1 of Cycle 2 or 3, resulting in dose delay were considered DLTs.

Time frame: Start of venetoclax administration (Cycle 1 Day 4 or 3 days after first CHOP dose) up to end of Cycle 2 (cycle length = 21 days)

Population: Safety population: All participants who enrolled in the study and received any amount of venetoclax or R-CHOP/G-CHOP were included in the safety population for safety analyses. Here, participants in the Dose Finding phase were analyzed.

Cmax was determined using the post-dose Cyclophosphamide plasma concentrations on Cycle 1 Day 1.

Time frame: End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)

Population: PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. Given a single dose strength of Cyclophosphamide was administered across the different Venetoclax dose groups and treatment arms, hence the data are presented as an overall summary.

Cmax was determined using the post-dose Doxorubicin plasma concentrations.

Time frame: End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)

Population: PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. Given a single dose strength of Doxorubicin was administered across the different Venetoclax dose groups and treatment arms, hence the data are presented as an overall summary.

Cmax was determined using the post-dose obinutuzumab plasma concentrations at the 800 mg Venetoclax Dose using the end of infusion time point on Cycle 1 Day 1.

Time frame: End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)

Population: PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. The Cmax of obinutuzumab is presented at the 800 mg Venetoclax dose group. Hence, the data is not presented by the treatment arms/Venetoclax dose groups.

Progressive disease (PD) was determined using the modified Lugano classification criteria. For PET-CT-based PD: Score 4 (uptake moderately \> liver) or 5 (uptake markedly higher than liver and/or new lesions) with an increase in intensity of uptake from baseline in target nodes and nodal lesions, new FDG-uptake foci of extranodal lesions consistent with lymphoma at interim or end-of-treatment assessment, no non-measured lesions, new FDG-uptake foci consistent with lymphoma, new or recurrent FDG-uptake foci in bone marrow. For CT-based PD: \>/= 50% decrease in SPD of up to 6 target measureable nodes and extranodal sites; non-measured lesion should be absent/normal, have regressed, but not increased; no new lesions.

Time frame: Month 12

Population: Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available.

CR was defined as follows according to modified Lugano classification for CT-based response: Target nodes/nodal masses must have regressed to \</= 1.5 cm in longest transverse diameter of a lesion (LDi), no extra-lymphatic sites of disease, absence of non-measured lesions, organ enlargement must have regressed to normal, no new lesions, and if the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy.

Time frame: Baseline up to end of treatment (approx. 6 months)

Population: Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available.

Objective Response defined as PR (partial response) or CR (complete response) at end of treatment. CR: Lymph nodes and extra-lymphatic sites with score 1, 2 or 3 on a 5-point scale (with a higher score being a worse outcome). No evidence of fluorodeoxyglucose (FDG)-uptake disease in marrow. If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: Lymph nodes and extralymphatic sites with score of 4 or 5 on the 5-point scale with reduced uptake compared with baseline and residual mass(es) of any size. CT-based response criteria for PR must also be met. No new lesions. In bone marrow residual uptake could be higher than in normal marrow but must be reduced compared with baseline; persistent focal changes in the marrow to be considered for further evaluation with magnetic resonance imaging (MRI) or biopsy or an interval scan. OR=PR+CR

Time frame: Baseline to end of treatment (up to approximately 6 months)

Population: Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available.

AUC was determined based on measurement of Predisone concentrations in plasma over time.

Time frame: Predose (within 30 minutes) and 0.5, 1, 2, 4, 6 Hr after prednisone dose on Day 1 of Cycle 1 and 2 (cycle length = 21 days)

Population: PK evaluable population: All participants who received study drug and provided at least one post-treatment PK sample. A similar dose strength of prednisone (100 mg) was administered across the treatment arms/venetoclax dose groups. Hence, the data are presented as an overall summary in Cycles 1 and 2.

Cmax was determined based on measurement of Predisone concentrations in plasma over time.

Time frame: Predose (within 30 minutes) and 0.5, 1, 2, 4, 6 Hr after prednisone dose on Day 1 of Cycle 1 and 2 (cycle length = 21 days)

Population: PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. A similar dose strength of prednisone (100 mg) was administered across the treatment arms/venetoclax dose groups. Hence, the data are presented as an overall summary in Cycles 1 and 2.

Tmax was determined based on measurement of Predisone concentrations in plasma over time.

Time frame: Predose (within 30 minutes) and 0.5, 1, 2, 4, 6 Hr after prednisone dose on Day 1 of Cycle 1 and 2 (cycle length = 21 days)

Population: PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. A similar dose strength of prednisone (100 mg) was administered across the treatment arms/venetoclax dose groups. Hence, the data are presented as an overall summary in Cycles 1 and 2.

Dose intensity was categorized as \< 80%, 80% to \< 85%, 85% to \< 90%, or \>/= 90%.

Time frame: Baseline up to Cycle 6 (cycle length = 21 days)

Population: Safety population: All patients who enrolled in the study and received any amount of venetoclax or R-CHOP/G-CHOP were included in the safety population for safety analyses

Cmax was determined using the post-dose rituximab plasma concentrations at the 800 mg Venetoclax Dose using the end of infusion time point on Cycle 1 Day 1.

Time frame: End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)

Population: PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. The Cmax of rituximab is presented at the 800 mg Venetoclax dose group. Hence, the data is not presented by the treatment arms/Venetoclax dose groups.

Cmin was determined using the pre-dose rituximab plasma concentrations at the 800 mg Venetoclax Dose on Day 1 of Cycle 2.

Time frame: Pre-dose on Cycle 2 Day 1 (cycle length = 21 days)

Population: PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. The Cmin of rituximab is presented at the 800 mg Venetoclax dose group. Hence, the data is not presented by the treatment arms/Venetoclax dose groups.

Maintenance of relative dose intensity was defined as a dose intensity of \>/= 90%.

Time frame: Baseline up to Cycle 6 (cycle length = 21 days)

Population: Safety population: All patients who enrolled in the study and received any amount of venetoclax or R-CHOP/G-CHOP were included in the safety population for safety analyses. Overall R-CHOP and G-CHOP arms were analyzed for this outcome measure.

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Time frame: Baseline up to approximately 36 months

Population: Safety population: All patients who enrolled in the study and received any amount of venetoclax or R-CHOP/G-CHOP were included in the safety population for safety analyses

AUC was calculated based on measurement of venetoclax concentration in plasma over time. Venetoclax exposure was pooled across Phase I and II for the R-CHOP 800 mg cohorts. Data are reported as hour\*micrograms per milliliter (hr\*mcg/mL)

Time frame: Predose (within 30 minutes) & 2, 4, 6, 8 hours (Hr) postdose on Cycle 1 Day 4 (cycle length = 21 days)

Population: PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. Reporting according to study drug received. One participant mistakenly received only 100 mg instead of the planned 200 mg dose and was reported in a separate arm for PK outcome measures.

Cmax was determined based on measurement of venetoclax concentrations in plasma over time. Venetoclax exposure was pooled across Phase I and II for the R-CHOP 800 mg cohorts. Data are reported as micrograms per milliliter

Time frame: Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)

Population: PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. Reporting according to study drug received. One participant mistakenly received only 100 mg instead of the planned 200 mg dose and was reported in a separate arm for PK outcome measures.

Cmin was determined based on measurement of venetoclax concentrations in plasma over time. Venetoclax exposure was pooled across Phase I and II for the R-CHOP 800 mg cohorts.

Time frame: Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)

Population: PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. Reporting according to study drug received. One participant mistakenly received only 100 mg instead of the planned 200 mg dose and was reported in a separate arm for PK outcome measures.

Tmax was determined based on measurement of venetoclax concentrations in plasma over time. Venetoclax exposure was pooled across Phase I and II for the R-CHOP 800 mg cohorts.

Time frame: Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)

Population: PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. Reporting according to study drug received. One participant mistakenly received only 100 mg instead of the planned 200 mg dose and was reported in a separate arm for PK outcome measures.

Cmax was determined using the post-dose Vincristine plasma concentrations.

Time frame: End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)

Population: PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. Given a single dose strength of Vincristine was administered across the different Venetoclax dose groups and treatment arms, hence the data are presented as an overall summary.