Ibrutinib Plus Venetoclax in Subjects With Treatment-naive Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL)

MRD Cohort: Duration of Response (DOR) at 42 Months Landmark Time

Duration of response was calculated for participants achieving a response (CR, CRi, nPR, PR) based on 2008 IWCLL response criteria (Halleck et al.) and defined as the interval between the date of initial documentation of a response including PR with lymphocytosis, until disease progression (PD) or death from any cause, whichever occurred first. As the median DOR was not reached as of 67.0 months study follow-up, the Kaplan-Meier estimate of DOR at 42 months landmark time was presented. Median follow up duration for the individual MRD Cohort treatment arms: Confirmed uMRD Ibrutinib arm 69.1 months; Confirmed uMRD Placebo arm 67.4 months; uMRD Not Confirmed Ibrutinib arm 47.9 months; uMRD Not Confirmed Ibrutinib + Venetoclax arm 47.9 months.

Time frame: From initial documentation of a response until PD or death from any cause, whichever occurs first, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)

MRD Cohort: MRD-Negativity Rate

MRD negativity rate is defined as the percentage of participants achieving MRD negativity, which is defined as \<1 CLL cell per 10,000 leukocytes (\<1 x 10\^-4) as assessed by flow cytometry of a peripheral blood (PB) or bone marrow (BM) aspirate sample per central laboratory on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurs earlier. Median follow up duration for the individual MRD Cohort treatment arms: Confirmed uMRD Ibrutinib arm 69.1 months; Confirmed uMRD Placebo arm 67.4 months; uMRD Not Confirmed Ibrutinib arm 47.9 months; uMRD Not Confirmed Ibrutinib + Venetoclax arm 47.9 months.

Time frame: From randomization date until before any subsequent antineoplastic therapy, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)

MRD Cohort: Tumor Lysis Syndrome (TLS) Risk Reduction Rate With 3-Cycle Ibrutinib Lead-In (Percentage of Participants No Longer High Risk After 3-cycle Lead-in)

TLS risk reduction was summarized by the percentage of participants with TLS risk reduced from high at baseline to medium or low after ibrutinib lead-in. A reduction in TLS risk from high risk to medium or low risk is clinically meaningful because there is a reduction in the extent of TLS monitoring and risk of hospitalization. TLS risk category is defined as the tumor burden category, where: Low=All lymph nodes (LN) \< 5 cm AND absolute lymphocyte count (ALC) \< 25 x 10\^9/L; Medium=Any LN 5 cm to \< 10 cm OR ALC ≥ 25 x 10\^9/L; High=Any LN ≥ 10 cm OR ALC ≥ 25 x10\^9/L AND any LN ≥ 5 cm.

Time frame: Baseline, and last post-baseline value on or prior to venetoclax first dose date (cycle 4 day 1) or, for participants who never received venetoclax, the post-baseline value closest to cycle 4 day 1 (i.e. 84 days after the first dose date of ibrutinib).

MRD Cohort: Kaplan-Meier Estimate of Progression Free Survival (PFS) Rate at 48 Months Landmark Time

PFS was defined as time from the first dose date of study treatment until disease progression (PD) or death from any cause, whichever occurs first. Assessment of PD was conducted in accordance with the 2008 IWCLL criteria (Halleck et al). As the median PFS was not reached as of the overall median 67.0 months study follow-up, the Kaplan-Meier estimate of PFS rate at 48 months landmark time was presented. Median follow up duration for the individual MRD Cohort treatment arms: Confirmed uMRD Ibrutinib arm 69.1 months; Confirmed uMRD Placebo arm 67.4 months; uMRD Not Confirmed Ibrutinib arm 47.9 months; uMRD Not Confirmed Ibrutinib + Venetoclax arm 47.9 months.

Time frame: From the first dose of ibrutinib to the first confirmed PD or death, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)

MRD Cohort: Kaplan-Meier Estimate of Overall Survival (OS) Rate at 48 Months Landmark Time

OS is defined as the time from the first dose date of study treatment until date of death due to any cause. As the median OS was not reached as of the overall median 67.0 months study follow-up, the Kaplan-Meier estimate of OS rate at 48 months landmark time was presented. Median follow up duration for the individual MRD Cohort treatment arms: Confirmed uMRD: Randomized to Ibrutinib=69.1 months; Confirmed uMRD: Randomized to Placebo=67.4 months; uMRD Not Confirmed: Randomized to Open-Label Ibrutinib=47.9 months; uMRD Not Confirmed: Randomized to Open-Label Ibrutinib + Venetoclax=47.9 months.

Time frame: From the first dose of ibrutinib to time of death, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)

MRD Cohort: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs

An adverse event (AE) is any untoward medical occurrence, which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires unplanned in-patient hospitalization \>24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. Severity of events were graded according to the Common Terminology Criteria for Adverse Events version 4.03: mild=grade1, moderate=grade 2, severe=grade 3, life-threatening=grade 4, death=grade 5. Causal relation of study drug and event was assessed as not related, unlikely, possibly or probably related to the study drug.

Time frame: From first dose until 30 days following last dose of study drug. Overall median treatment duration for the MRD cohort was 45.1 months.

FD Cohort: ORR

ORR is defined as the percentage of participants who achieve a best overall response CR, CRi, nPR, PR, or PRL as evaluated by investigator using 2008 IWCLL criteria (Halleck et al.). Participants who did not have any postbaseline response assessment were considered as non-responders. This table is based on response assessments performed on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurs earlier. Kaplan-Meier estimate.

Time frame: From the first dose of ibrutinib to the first confirmed PD, for a median follow-up of 69.0 months.

FD Cohort: DOR at 60 Months Landmark Time

Duration of response was calculated for participants achieving a response (CR, CRi, nPR, PR) based on 2008 IWCLL response criteria (Halleck et al.) and defined as the interval between the date of initial documentation of a response including PR with lymphocytosis, until disease progression (PD) or death from any cause, whichever occurred first. As the median DOR was not reached as of the median 27.9 months study follow-up, the Kaplan-Meier estimate of DOR at 60 months landmark time was presented.

Time frame: From initial documentation of a response until PD or death from any cause, whichever occurs first, for a median follow-up of 69.0 months.

FD Cohort: MRD Negativity Rate

MRD negativity rate is defined as the percentage of participants achieving MRD negativity, which is defined as \<1 CLL cell per 10,000 leukocytes (\<1 x 10\^-4) as assessed by flow cytometry of a peripheral blood (PB) or bone marrow (BM) aspirate sample per central laboratory on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurs earlier.

Time frame: From randomization date until before any subsequent antineoplastic therapy, for a median follow-up of 69.0 months.

FD Cohort: Kaplan-Meier Estimate of PFS Rate at 66 Months Landmark Time

PFS was defined as time from the first dose date of study treatment until disease progression (PD) or death from any cause, whichever occurs first. Assessment of PD was conducted in accordance with the 2008 IWCLL criteria (Halleck et al). As the median PFS was not reached as of the median 69.0 months study follow-up, the Kaplan-Meier estimate of PFS rate at 66 months landmark time was presented.

Time frame: From the first dose of ibrutinib to the first confirmed PD or death, for an median follow-up of 69.0 months.

FD Cohort: Kaplan-Meier Estimate of OS Rate at 66 Months Landmark Time

OS is defined as the time from the first dose date of study treatment until date of death due to any cause. As the median OS was not reached as of the median 69.0 months study follow-up, the Kaplan-Meier estimate of OS rate at 66 months landmark time was presented.

Time frame: From the first dose of ibrutinib to time of death, for a median follow-up of 69.0 months.

FD Cohort: TLS Risk Reduction Rate With 3-Cycle Ibrutinib Lead-In (Percentage of Participants No Longer High Risk After 3-cycle Lead-in)

TLS risk reduction was summarized by the percentage of participants with TLS risk reduced from high at baseline to medium or low after ibrutinib lead-in. A reduction in TLS risk from high risk to medium or low risk is clinically meaningful because there is a reduction in the extent of TLS monitoring and risk of hospitalization. TLS risk category is defined as the tumor burden category, where: Low=All lymph nodes (LN) \< 5 cm AND absolute lymphocyte count (ALC) \< 25 x 10\^9/L; Medium=Any LN 5 cm to \< 10 cm OR ALC ≥ 25 x 10\^9/L; High=Any LN ≥ 10 cm OR ALC ≥ 25 x10\^9/L AND any LN ≥ 5 cm.

Time frame: Baseline, and last post-baseline value on or prior to venetoclax first dose date (cycle 4 day 1) or, for participants who never received venetoclax, the post-baseline value closest to cycle 4 day 1 (i.e. 84 days after the first dose date of ibrutinib).

FD Cohort: Percentage of Participants With TEAEs, Treatment-Emergent SAEs, and Discontinuations Due to TEAEs

An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires unplanned in-patient hospitalization \>24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. Severity of events were graded according to the Common Terminology Criteria for Adverse Events version 4.03: mild=grade1, moderate=grade 2, severe=grade 3, life-threatening=grade 4, death=grade 5. Causal relation of study drug and event was assessed as not related, unlikely, possibly or probably related to the study drug.

Time frame: From first dose until 30 days following last dose of study drug. Overall median treatment duration for the FD cohort was 13.8 months.

MRD Cohort: Pharmacokinetics (PK) of Ibrutinib When Dosed in Combination With Venetoclax: Observed Maximum Concentration (Cmax)

Time frame: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Time to Cmax (Tmax); Time of Last Measurable Concentration (Tlast); Terminal Elimination Half-Life (t1/2,Term)

Time frame: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Area Under the Plasma Concentration-Time Curve (AUC) Over the Last 24-hour Dosing Interval (AUC0-24h); AUC From Time Zero to the Time of Last Quantifiable Concentration (AUClast)

Time frame: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Terminal Elimination Rate Constant (λz)

Time frame: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Apparent Total Clearance at Steady-State (CLss/F)

Time frame: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: Cmax

Time frame: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: Tmax

Time frame: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: AUC0-24h

Time frame: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: CLss/F

Time frame: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)