A Multi-Center Study of Ibrutinib in Combination With Obinutuzumab Versus Chlorambucil in Combination With Obinutuzumab in Patients With Treatment naïve Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

Primary Analysis: PFS in High-Risk Sub-Population (del17p/TP53 Mutation/Del 11q) Based on IRC Assessment - Kaplan Meier Landmark Estimates at Month 30

PFS was analyzed within the high-risk sub-population of participants with del17p or TP53 mutation or del 11q at baseline per central lab results. PFS was defined as time from the date randomization to the date of first IRC-confirmed PD or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the IWCLL 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of PD was not considered progressive disease. As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 30 months (that is, the estimated percentage of participants with progression-free survival at Month 30) are presented.

Time frame: Month 30 (Median follow-up time was 31.3 months at the time of the primary analysis [data cutoff date: 26 March 2018]).

Primary Analysis: Rate of Sustained Hemoglobin Improvement

Percentage of participants with sustained hemoglobin improvement, defined as hemoglobin increase ≥ 2 g/dL over baseline continuously for ≥ 56 days without blood transfusions or growth factors.

Time frame: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).

Primary Analysis: Rate of Minimal Residual Disease (MRD)-Negative Response

Percentage of participants who achieved MRD-negative response, defined as \< 1 CLL cell per 10,000 leukocytes as assessed by flow cytometry of a bone marrow aspirate per central laboratory. MRD samples were collected before initiation of subsequent antineoplastic treatment and MRD status was reported by central lab within 5 days after collection date. Participants with missing MRD data were considered non-responders.

Time frame: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).

Primary Analysis: Overall Response Rate (ORR) Based on IRC Assessment

ORR, defined as the percentage of participants achieving a best overall response of protocol-specified complete response (CR), CR with incomplete blood count recovery (CRi), nodular partial response (nPR), or partial response (PR) per IRC assessment at or prior to initiation of subsequent antineoplastic therapy. Assessment of response included physical examination, radiographic imaging, and evaluation of blood and marrow (if applicable), evaluated in accordance with the IWCLL 2008 criteria (Halleck et al). CR, CRi, nPR, and PR required confirmation with 2 consecutive assessments that were at least 56 days apart and no use of blood supportive product and/or growth factor during this period. Kaplan-Meier estimate.

Time frame: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).

Primary Analysis: Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 30

OS, defined as the time from the date of randomization to the date of death from any cause. All deaths observed as the time of the analysis were considered as events. For participants who were not known to have died at the time of the analysis, OS data were censored at the date last known alive. As the median OS was not reached in either treatment arm at the time of the analysis, Kaplan Meier landmark estimates of the OS rate (that is, the estimated percentage of participants still surviving at Month 30 \[primary analysis\]) are presented.

Time frame: Month 30 (Median follow-up time was 31.3 months at the time of the primary analysis [data cutoff date: 26 March 2018]).

Primary Analysis: Rate of Grade ≥ 3 or Serious Infusion-Related Reaction (IRR) Adverse Events

Percentage of participants experiencing grade ≥ 3 (severe or life threatening) or serious IRR adverse events that started on the day of an obinutuzumab infusion and were assessed as related or possibly related to obinutuzumab. Categories included those events with the Medical Dictionary for Regulatory Activities (MedDRA) dictionary preferred term of IRR and those events which are among the customized standardized MedDRA query (SMQ) for IRR.

Time frame: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).

Primary Analysis: Rate of Sustained Platelet Improvement

Percentage of participants with platelet counts increase ≥ 50% over baseline continuously for ≥ 56 days without blood transfusion or growth factors.

Time frame: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).

Primary Analysis: Rate of Clinically Meaningful Improvement in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EuroQol Five-Dimension (EQ-5D-5L)

Percentage of participants with EQ-5D-5L utility score increase ≥ 0.08 points over baseline at or prior to initiation of subsequent antineoplastic therapy. The EQ-5D-5L is a standardized non-disease specific instrument for describing and valuing health-related quality of life, comprising 5 dimensions of health (mobility, self -care, usual activities, pain/discomfort, and anxiety/depression) to describe the participant's current health state. Each dimension comprises 5 levels with corresponding numeric scores, where 1 indicates no problems, and 5 indicates extreme problems. A unique EQ-5D-5L health state is defined by combining the numeric level scores for each of the 5 dimensions and the total score is normalized from -0.594 to 1.000, with higher scores representing a better health state. An increase in the EQ-5D-5L total score indicates improvement. Participants with missing EQ-5D-5L data were considered not achieving clinically meaningful improvement.

Time frame: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).

Final Analysis: PFS in High-Risk Population (del17p/TP53 Mutation/Del 11q/Unmutated Immunoglobulin Heavy Chain Variable Region [IGHV]) Based on Investigator Assessment - Kaplan Meier Landmark Estimates at Month 48

PFS was analyzed within the high-risk population of participants with del17p or TP53 mutation or del 11q or IGHV unmutated at baseline per central lab results. PFS was defined as time from the date randomization to the date of first investigator-confirmed PD or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the IWCLL 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of PD was not considered progressive disease. As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 48 months (that is, the estimated percentage of participants with progression-free survival at Month 48) are presented.

Time frame: Month 48 (Median follow-up time was 44.6 months at the time of the final analysis [data cutoff date: 17 October 2019]).

Final Analysis: Rate of Sustained Hemoglobin Improvement

Percentage of participants with sustained hemoglobin improvement, defined as hemoglobin increase ≥ 2 g/dL over baseline continuously for ≥ 56 days without blood transfusions or growth factors.

Time frame: Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).

Final Analysis: Rate of Minimal Residual Disease (MRD)-Negative Response

Percentage of participants who achieved MRD-negative response, defined as \< 1 CLL cell per 10,000 leukocytes as assessed by flow cytometry of a bone marrow aspirate per central laboratory. MRD samples were collected before initiation of subsequent antineoplastic treatment and MRD status was reported by central lab within 5 days after collection date. Participants with missing MRD data were considered non-responders.

Time frame: Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).

Final Analysis: ORR Based on Investigator Assessment

ORR, defined as the percentage of participants achieving a best overall response of protocol-specified CR, CRi, nPR or PR per investigator assessment at or prior to initiation of subsequent antineoplastic therapy. Assessment of response included physical examination, radiographic imaging, and evaluation of blood and marrow (if applicable), evaluated in accordance with the IWCLL 2008 criteria (Halleck et al). CR, CRi, nPR, and PR required confirmation with 2 consecutive assessments that were at least 56 days apart and no use of blood supportive product and/or growth factor during this period. Kaplan-Meier estimate.

Time frame: Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).

Final Analysis: Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 48

OS, defined as the time from the date of randomization to the date of death from any cause. All deaths observed as the time of the analysis were considered as events. For participants who were not known to have died at the time of the analysis, OS data were censored at the date last known alive. As the median OS was not reached in either treatment arm at the time of the analysis, Kaplan Meier point estimates of the OS rate (that is, the estimated percentage of participants still surviving at Month 48 \[final analysis\]) are presented.

Time frame: Month 48 (Median follow-up time was 44.6 months at the time of the final analysis [data cutoff date: 17 October 2019]).

Final Analysis: Rate of Sustained Platelet Improvement

Percentage of participants with platelet counts increase ≥ 50% over baseline continuously for ≥ 56 days without blood transfusion or growth factors.

Time frame: Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).