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

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.

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

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.

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)

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.

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

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.

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

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

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

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.

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

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.

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

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

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

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

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.

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.

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.

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

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