A Study of Obinutuzumab in Chinese Participants With CD20+ Malignant Disease

DLBCL and FL are sub-types of Non-Hodgkin's Lymphoma (NHL) and time frame for these 2 groups was presented under NHL. For CLL, pharmacokinetic (PK) parameters were from Cycle 1 Day 1 and Day 2 dosing, due to split dosing.

DLBCL and FL are sub-types of NHL and time frame for these 2 groups was presented under NHL. For CLL, PK parameters were from Cycle 1 Day 1 and Day 2 dosing, due to split dosing.

Half-life is the time measured for the serum concentration of study drug to decrease (Dec) by one half.

Vss reflects the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

CR: 1) Disappearance of clinical and radiographic evidence of disease, related symptoms and normalization of biochemical abnormalities definitely assignable to NHL, 2) Lymph nodes (LN) and nodal masses regressed to normal size after therapy (AT) (≤1.5 centimeters [cm] in their greatest transverse diameter [GTD] for LN greater than (>) 1.5 cm before therapy [BT]). LN that were 1.1 to 1.5 cm in their GTD BT decreased to ≤1 cm in GTD AT, or >75% in the sum of the products (SPD) of the GTD, 3) Enlarged spleen regressed in size and not palpable, 4) Absence of macroscopic nodules, 5) Enlarged organs decreased in size, and 6) If the bone marrow (BM) was involved, the infiltrate must be cleared on repeat BM aspirate and biopsy. CRu included those participants who met CR Criteria 1 and 3, but with 1 or more of the following features: a) A residual LN mass >1.5 cm in GTD that has regressed by more than 75% in their SPD, and b) Indeterminate BM (increased [Inc] number or size of aggregates).

PR: 1) ≥50% decrease in SPD of the 6 largest dominant nodes/nodal masses. These nodes or masses selected according to the following features: a) clearly measurable in ≥2 perpendicular dimensions, b) from as disparate regions of the body as possible, and c) included mediastinal and retroperitoneal areas of disease. 2) No increase in size of other nodes (liver/spleen). 3) Splenic and hepatic nodules regressed by ≥50% in SPD. 4) With exception of splenic and hepatic nodules, involvement of other organs was considered assessable and not measurable disease. 5) BM assessment is irrelevant for determination of a PR because it was assessable and not measurable disease; however, if positive, the cell type was specified. 6) No new sites of disease. PD requires the following: 1) ≥50% increase from nadir in the SPD of any previously identified abnormal node for PRs or nonresponders. 2) Appearance of any new lesion during or at the end of therapy. SD is defined as less than a PR but not PD.

CR: 1) Disappearance of clinical and radiographic evidence of disease, related symptoms and normalization of biochemical abnormalities definitely assignable to NHL, 2) LN and nodal masses regressed to normal size AT (≤1.5 cm] in their GTD for LN >1.5 cm BT). LN that were 1.1 to 1.5 cm in their GTD BT decreased to ≤1 cm in GTD AT, or >75% in the SPD of the GTD, 3) Enlarged spleen regressed in size and not palpable, 4) Absence of macroscopic nodules in any organs, 5) Enlarged organs decreased in size, and 6) If the BM was involved, the infiltrate must be cleared on repeat BM aspirate and biopsy. CRu included those participants who met CR Criteria 1 and 3, but with 1 or more of the following features: a) A residual LN mass >1.5 cm in GTD that has regressed by more than 75% in their SPD, b) Indeterminate BM (increased number or size of aggregates).

PR: 1) ≥50% decrease in SPD of the 6 largest dominant nodes/nodal masses. These nodes or masses selected according to the following features: a) clearly measurable in ≥2 perpendicular dimensions, b) from as disparate regions of the body as possible, and c) included mediastinal and retroperitoneal areas of disease. 2) No increase in size of other nodes (liver/spleen). 3) Splenic and hepatic nodules regressed by ≥50% in SPD. 4) With exception of splenic and hepatic nodules, involvement of other organs was considered assessable and not measurable disease. 5) BM assessment is irrelevant for determination of a PR because it was assessable and not measurable disease; however, if positive, the cell type was specified. 6) No new sites of disease. PD requires the following: 1) ≥50% increase from nadir in the SPD of any previously identified abnormal node for PRs or nonresponders. 2) Appearance of any new lesion during or at the end of therapy. SD is defined as less than a PR but not PD.

CRe required the following criteria as assessed, at least 2 months from completing therapy: a) peripheral blood lymphocytes (PBL) less than (<) 4 x 10^9/L, b) Absence of significant lymphadenopathy (LD) by physical examination (PE), c) No hepatomegaly/splenomegaly (HM/SM) by PE, d) Absence of constitutional symptoms and e) Blood counts above the following values (i. Neutrophils [Neu] >1.5 x 10^9/L without the need for exogenous growth factors [EGF], ii. Platelets (Plt) >100 x 10^9/L without the need for EGF, and iii. Hemoglobin (Hb) >11.0 g/dL without blood transfusion or need for erythropoietin), and d) Once clinical and laboratory reports demonstrated CRe, a BM aspirate and biopsy was performed at least 2 months after the last treatment; to define a CRe, BM sample should be normocellular for age, <30% of the cells being PBL and lymphoid nodules absent. CRi: CRe but persistent anemia/thrombocytopenia/neutropenia unrelated to CLL, but related to drug toxicity.

Group A: a)Dec LN size by ≥50% either in SPD of 6 LN or largest diameter of enlarged LN (ELN) detected BT, b)Reduction (Red) in BT enlargement of liver, c)Red in BT enlargement of spleen, d)Dec in PBL by ≥50% from baseline, e)A 50% Red in BM infiltrate or B-lymphoid nodules in BM and f)No Inc in any LN and no new ELN. Group B: a)Plt count=100,000/µL or Inc of ≥50% over baseline, b)Hb >11 g/dL or ≥50% Inc over baseline, c)Neu > 1500/µL or > 50% Inc over baseline. PR is considered as achieved if 2 of Group A criteria and 1 of Group B criteria were met for ≥2 months. PD is defined as LD (appearance of new lesion [ELN], SM, HM or other organ infiltrates) or Inc by ≥50% in greatest determined diameter of any previous site or Inc in previously noted enlargement of liver/spleen by ≥50% or new appearance of HM/SM or an Inc in number of PBL ≥50% or transformation to a more aggressive histology or occurrence of cytopenia attributable to CLL. SD is defined as less than a PR but is not PD.

CRe required the following criteria as assessed, at least 2 months from completing therapy: a) PBL <4 x 10^9/L, b) Absence of significant LD by PE, c) No HM/SM by PE, d) Absence of constitutional symptoms and e) Blood counts above the following values (i. Neu >1.5 x 10^9/L without the need for EGF, ii. Plt >100 x 10^9/L without the need for EGF, and iii. Hb >11.0 g/dL without blood transfusion or need for EGF, and d) Once clinical and laboratory reports demonstrated CRe, a BM aspirate and biopsy was performed at least 2 months after the last treatment; to define a CRe, BM sample should be normocellular for age, <30% of the cells being PBL and lymphoid nodules absent. CRi: CRe but persistent anemia/thrombocytopenia/neutropenia unrelated to CLL, but related to drug toxicity.

Group A: a)Dec LN size by ≥50% either in SPD of 6 LN or largest diameter of ELN detected BT, b)Red in BT enlargement of liver, c)Red in BT enlargement of spleen, d)Dec in PBL by ≥50% from baseline, e)A 50% Red in BM infiltrate or B-lymphoid nodules in BM and f)No Inc in any LN and no new ELN. Group B: a)Plt count=100,000/µL or Inc of ≥50% over baseline, b)Hb >11 g/dL or ≥50% Inc over baseline, c)Neu > 1500/µL or > 50% Inc over baseline. PR is considered as achieved if 2 of Group A criteria and 1 of Group B criteria were met for ≥2 months. PD is defined as LD (appearance of new lesion [ELN], SM, HM or other organ infiltrates) or Inc by ≥50% in greatest determined diameter of any previous site or Inc in previously noted enlargement of liver/spleen by ≥50% or new appearance of HM/SM or an Inc in number of PBL ≥50% or transformation to a more aggressive histology or occurrence of cytopenia attributable to CLL. SD is defined as less than a PR but is not PD.

For the detection of HAHA, serum samples were initially analyzed using a validated enzyme linked immunosorbent assay (ELISA) method (screening assay, tier 1). The lower limit of quantification (LLOQ) in undiluted serum was 18.4 nanograms per milliliter (ng/mL). The precision ranged from 4.85 percent (%) to 16.0%. In serum samples found positive, the presence of specific anti-obinutuzumab antibodies was confirmed or excluded using the same ELISA method with an appropriate immunocompetition step (addition of excess obinutuzumab, confirmation assay, tier 2). Samples were confirmed as containing specific anti-obinutuzumab antibodies if there was a signal reduction ≥85.7% in the presence of obinutuzumab.

Serum concentrations of HACA against rituximab were determined by ELISA. The LLOQ in undiluted serum was 5.00 relative units per milliliter (RU/mL). The precision and accuracy of the assay, as determined from the analysis of quality control samples, were satisfactory throughout the study; precision ranged from 6.4% to 13.6% and accuracy ranged from 88.2% to 94.8%.

Depletion is defined as cluster of differentiation (CD) 19+ B-cell count <0.07 x10^9/L.Recovery is defined as CD19+ B-cell equal to or greater than 0.07 x 10^9/L.

Depletion is defined as CD19+ B-cell count < 0.07 x 10^9/L. The duration of depletion is defined as the number of days between first assessment of B-cell depletion and the first assessment where CD19+ cell count returned to at least the depletion level from baseline and not followed by any further B-cell depletion. If participant did not return to above depletion level, then the cut off is at the time of last assessment.

Recovery is defined as CD19+ B-cell equal to or greater than 0.07 x 10^9/L. Time to recovery is defined as time between the beginning of depletion and first value after end of treatment that is equal or above 0.07x10^9/L and not exclusively followed by depleted values only. If participant did not return to above recovery level then set to Null.