Dose Escalation and Dose Expansion Study of Tirabrutinib in Combination With Other Targeted Anti-cancer Therapies in Adults With B-cell Malignancies

A Phase 1b Dose Escalation and Dose Expansion Study of Tirabrutinib (ONO/GS-4059) in Combination With Other Targeted Anti-cancer Therapies in Subjects With B-cell Malignancies

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02457598

Enrollment

203

Registered

2015-05-29

Start date

2015-06-16

Completion date

2024-09-25

Last updated

2025-06-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

B-cell Malignancies

Brief summary

The primary objectives of this study are to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of tirabrutinib (ONO/GS-4059) in combination with other targeted anti-cancer therapies and to evaluate the long-term safety of tirabrutinib as a monotherapy and in combination with other targeted anti-cancer therapies in adults with relapsed or refractory B-cell lymphoproliferative malignancies. This study consists of three parts: Dose Escalation, Dose Expansion, and Long-term Safety Monitoring. During the Dose Escalation phase, participants will be sequentially enrolled in a standard 3 + 3 dose escalation study design, to receive oral tirabrutinib combined with idelalisib entospletinib +/- obinutuzumab. The Dose Expansion Phase will enroll additional participants with a single B-cell lymphoproliferative malignancy disease type to further evaluate efficacy, safety, tolerability, PK, and pharmacodynamics. The Long-term Safety Monitoring phase will evaluate the long-term safety of tirabrutinib both as a monotherapy and in combination with other anti-cancer therapies. As of Amendment 9, all participants currently on the study who have no clinical evidence of disease progression will transition into long-term safety monitoring. Participants from the ongoing Study GS-US-401-1787 and participants who came off Study GS-US-401-1757 and Study GS-US-401-1787 but continued to receive treatment via named patient use (or individual expanded use) will be enrolled into the long-term safety monitoring group (Group VI). Participants enrolled in Group VI will continue the same treatment regimen in Study GS-US-401-1787 or named patient use (or individual expanded use). As of Protocol Amendment 8, the maximum treatment duration for any participant is an additional 6 years from the date of this amendment (ie. until November 2025). As of Amendment 9, entospletinib will be provided until 31 December 2020 to participants who are currently receiving entospletinib. Participants treated with entospletinib as part of a combination regimen with tirabrutinib will stop receiving entospletinib by 31 December 2020 but may continue to be treated with tirabrutinib monotherapy. Idelalisib will be provided as 50 mg tablets until 31 December 2020 and 100 mg tablets until study completion. Participants assigned to the 50 mg tablet will be given the option, at the investigator's discretion, to switch to 100 mg once daily idelalisib dose.

Interventions

DRUGTirabrutinib

Capsules or tablets administered orally

DRUGIdelalisib

Tablets administered orally twice daily

DRUGEntospletinib

Tablets administered orally

DRUGObinutuzumab

Administered intravenously

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Enrollment and treatment were parallel in different combinations used in the study.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Key Inclusion Criteria: * Diagnosis of follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), chronic lymphocytic leukemia (CLL) (meeting International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria 2008), mantle cell lymphoma (MCL), Waldenstrom's macroglobulinemia (WM), or non-germinal center B-cell lymphoma (GCB) diffuse large B-cell lymphoma (DLBCL) as documented by medical records on World Health Organization (WHO) criteria * Prior treatment for FL, MZL, SLL, MCL, WM with ≥ 2 or for CLL or non-GCB DLBCL ≥ 1 chemotherapy-based or immunotherapy-based regimen, and not transplant eligible and have had either progressive disease (PD) or no response to previous treatment * For diseases other than Waldenstrom's macroglobulinemia (WM), presence of radiographically measurable presence of ≥ 1 lesion that measures ≥ 2.0 cm in the longest dimension (LD) and ≥ 1.0 cm in the longest perpendicular dimension (LPD) * Eastern Cooperative Oncology Group (ECOG) ≤ 2 * Platelets ≥ 50 x 10\^9/L; Hb ≥ 8.0 g/dL; absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L * Without transfusion and growth factors within 7 days * Aspartate transaminase/alanine transaminase (AST/ALT) ≤ 2.5 x upper limit of normal (ULN) * Total bilirubin ≤ 1.5 x ULN * Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 mL/min * Not pregnant * Willingness and ability to comply with protocol-specified Pneumocystis jirovecii pneumonia (PJP) prophylaxis * Long-term Safety Monitoring group only (Group VI): * Currently enrolled in Study GS-US-401-1787 or previously enrolled in Study GS-US-401-1757 or Study GS-US-401-1787 and currently receiving continued treatment via named patient use * Continuing to benefit from the current treatment regimen in the opinion of the investigator/treating physician Key

Exclusion criteria

* Hepatitis B surface antigen (HBsAG) positive or hepatitis B core antibody positive * Hepatitis C virus (HCV) antibody positive * History of long QT syndrome or whose corrected QT(QTc) interval measured (Fridericia method) at screening is prolonged (\>450 ms) * Long-term Safety Monitoring group only (Group VI): * Evidence of clinical or radiological disease progression Note: Other protocol defined Inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Dose Limiting Toxicities (DLTs)	Up to 28 days	A DLT was defined as a ≥ Grade 3 AE that was assessed as related to study drug that occurred during the 28-day DLT assessment period with protocol-defined allowed exceptions. Any treatment-emergent adverse event (TEAE) that was, in the opinion of the Clinical Trial Steering Committee, of potential clinical significance such that further dosing exposed participants to unacceptable risk, was considered a DLT.
Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Week 12	ORR for Waldenstrom Macroglobulinemia(WM):CR+VGPR+PR+MPR. CR: Absence of serum monoclonal IgM protein; normal serum IgM level: complete resolution of extramedullary disease, morphologically normal bone marrow/aspirate and trephine biopsy. Very good partial response (VGPR):Detectable monoclonal IgM; ≥90% reduction in serum IgM; Complete resolution of extramedullary disease; No new signs/symptoms. PR: Monoclonal immunoglobulin M (IgM) protein is detectable ≥50% but \<90% reduction in serum IgM level from baseline; reduction of extramedullary disease; no new signs or symptoms of active disease. Minor response (MPR):Detectable monoclonal IgM; ≥25% but \<50% reduction in serum IgM; No progression of extramedullary disease; No new signs/symptoms. Clopper-Pearson method was used in analysis. Data is reported by disease type: WM; Follicular Lymphoma (FL);Mantle Cell Lymphoma (MCL);Small Lymphocytic Lymphoma (SLL);Marginal Zone Lymphoma (MZL);Diffuse Large B-Cell Lymphoma (DLBCL) as applicable.
ORR: Percentage of Participants With CR or PR in Participants With CLL at Week 24	Week 24	ORR was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR). CR and PR are defined in outcome measure#2. Clopper-Pearson method was used in outcome measure analysis. Percentages were rounded off.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	First dose up to last dose date (up to 441 weeks) plus 30 days	An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. TEAEs were defined as an AE that onset in the period from the first dose of study treatment to 30 days after the last dose of study treatment. Percentages were rounded off.

Secondary

Measure	Time frame	Description
Percentage of Participants Who Achieved Minimal Residual Negative Disease (< 1 Leukemia Cell/10,000 Leukocytes) During the Dose Escalation Phase and Dose Expansion Phase in Participants With CLL	Up to 281 weeks	Achieving Minimal Residual Disease was defined as \< 1 leukemia cell/10,000 leukocytes (10-4) in participants who have also achieved a CR. CR is defined in outcome measure #2.
Pharmacokinetic (PK) Parameter: AUCtau of Tirabrutinib 80 mg	Cycle 1 Day 8: Predose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours postdose	AUCtau was defined as concentration of drug over time. Area under the concentration verses time curve over the dosing interval (AUctau). The data for AUCtau is reported for tirabrutinib 80 mg as monotherapy and in combination with idelalisib 50 mg and 100 mg and entospletinib 200 mg and 400 mg.
PK Parameter: Cmax of Tirabrutinib 80 mg	Cycle 1 Day 8: Predose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours postdose	Cmax was defined as the maximum observed concentration of drug. The data for Cmax is reported for tirabrutinib 80 mg as monotherapy and in combination with idelalisib 50 mg and 100 mg and entospletinib 200 mg and 400 mg.
PK Parameter: AUCtau of Idelalisib When Given in Combination With Tirabrutinib	Cycle 1 Day 8: Predose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours postdose	AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Up to 281 weeks	ORR for WM is CR + VGPR + PR + MPR. CR, PR, VGPR and MPR are defined in outcome measure#2. Clopper-Pearson method was used in outcome measure analysis. Percentages were rounded off. Data is reported by disease type: CLL ; FL; MCL; MZL; SLL; WM; DLBCL.
PK Parameter: AUCtau of Metabolite of Idelalisib (GS-563117) When Given in Combination With Tirabrutinib	Cycle 1 Day 8: Predose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours postdose	AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: Cmax of Metabolite of Idelalisib (GS-563117) When Given in Combination With Tirabrutinib	Cycle 1 Day 8: Predose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours postdose	Cmax was defined as the maximum observed concentration of drug.
PK Parameter: AUCtau of Entospletinib When Given in Combination With Tirabrutinib	Cycle 1 Day 8: Predose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours postdose	AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: Cmax of Entospletinib When Given in Combination With Tirabrutinib	Cycle 1 Day 8: Predose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours postdose	Cmax was defined as the maximum observed concentration of drug.
PK Parameter: Cmax of Idelalisib When Given in Combination With Tirabrutinib	Cycle 1 Day 8: Predose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours postdose	Cmax was defined as the maximum observed concentration of drug.
Progression Free Survival (PFS) During the Dose Escalation Phase and Dose Expansion Phase	Up to 281 weeks	PFS was defined as the interval from the start of the study therapy to the earlier of the first documentation of definite disease progression (PD) or death from any cause. PD: ≥ 25% increase in serum IgM level from lowest nadir (requires confirmation) and/or progression in clinical features attributable to the disease. Kaplan-Meier (KM) estimate were used in outcome measure analysis. Data is reported by disease type: CLL; FL; MCL; MZL; other NHL; DLBCL.
Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Up to 281 weeks	DOR was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definite disease progression or death from any cause. CR and PR are defined in outcome measure# 2. PD is defined in outcome measure #6. KM estimates were used in outcome measure analysis. Data is reported by disease type: CLL; FL; MCL; MZL; SLL; WM; DLBCL
Time to Response (TTR) During the Dose Escalation Phase and Dose Expansion Phase	Up to 281 weeks	TTR was defined as the interval from start of treatment to the first documentation of CR or PR. CR and PR are defined in outcome measure# 2. Data is reported by disease type: CLL; FL; MCL; MZL; SLL; WM; DLBCL.

Countries

France, United Kingdom, United States

Participant flow

Recruitment details

Participants were enrolled at study sites in France, the United Kingdom and the United States.

Pre-assignment details

248 participants were screened. 203 participants were enrolled, 197 participants were enrolled to receive treatment in Combinations I to IV and Group V. 5 participants rolled over from another tirabrutinib study (GS-US-401-1787) and 1 from this study (GS-US-401-1757) was re-assigned to Group VI to continue with tirabrutinib and be monitored for long-term safety. Per pre-specified analysis, participants in Group VI were analyzed based on the disease type.

Participants by arm

Arm	Count
Combination I (Tirabrutinib 20 mg QD+ Idelalisib 50 mg BID) Participants received tirabrutinib 20 mg tablet once daily (QD) for up to 209 weeks and idelalisib 50 mg tablet twice daily (BID) orally for up to 120 weeks. Both drugs were administered for 28-day cycles.	3
Combination I (Tirabrutinib 40 mg QD+ Idelalisib 50 mg BID) Participants received tirabrutinib 40 mg tablet QD for up to 251 weeks and idelalisib 50 mg tablet BID orally, for up to 245 weeks. Both drugs were administered for 28-day cycles.	8
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID) Participants received tirabrutinib 80 mg tablet QD for up to 212 weeks and idelalisib 50 mg tablet BID orally, for up to 26 weeks. Both drugs were administered for 28-day cycles.	4
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD) Participants received tirabrutinib 80 mg tablet QD for up to 227 weeks and idelalisib 100 mg tablet QD orally, for up to 227 weeks. Both drugs were administered for 28-day cycles.	25
Combination I (Tirabrutinib 160 mg QD+ Idelalisib 100 mg QD) Participants received tirabrutinib 160 mg tablet QD for up to 151 weeks and idelalisib 100 mg tablet QD orally, for up to 151 weeks. Both drugs were administered for 28-day cycles.	9
Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID) Participants received tirabrutinib 20 mg tablet BID for up to 207 weeks and idelalisib 50 mg tablet BID orally, for up to 207 weeks. Both drugs were administered for 28-day cycles.	5
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 200 mg QD) Participants received tirabrutinib 40 mg tablet QD for up to 250 weeks and entospletinib 200 mg tablet QD orally, for up to 250 weeks. Both drugs were administered for 28-day cycles.	3
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 200 mg QD) Participants received tirabrutinib 80 mg tablet QD for up to 234 weeks and entospletinib 200 mg tablet QD orally, for up to 220 weeks. Both drugs were administered for 28-day cycles.	6
Combination II (Tirabrutinib 150 mg QD+ Entospletinib 200 mg QD) Participants received tirabrutinib 150 mg tablet QD for up to 103 weeks and entospletinib 200 mg tablet QD orally, for up to 88 weeks. Both drugs were administered for 28-day cycles.	3
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 400 mg QD) Participants received tirabrutinib 40 mg tablet QD for up to 119 weeks and entospletinib 400 mg tablet QD orally, for up to 119 weeks. Both drugs were administered for 28-day cycles.	3
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD) Participants received tirabrutinib 80 mg tablet QD for up to 232 weeks and entospletinib 400 mg tablet QD orally, for up to 229 weeks. Both drugs were administered for 28-day cycles.	78
Combination II (Tirabrutinib 160 mg QD+ Entospletinib 400 mg QD) Participants received tirabrutinib 160 mg tablet QD for up to 44 weeks and entospletinib 400 mg tablet QD orally, for up to 44 weeks. Both drugs were administered for 28-day cycles.	8
Combination III (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD+ Obinutuzumab 1000 mg) Participants received tirabrutinib 80 mg tablet QD for up to 199 weeks; Idelalisib 100 mg tablet QD orally for up to 199 weeks, and single dose of obinutuzumab 1000 mg intravenously (IV) for up to 22 weeks. All drugs were administered for 28-day cycles.	6
Combination IV (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD+Obinutuzumab 1000 mg) Participants received tirabrutinib 80 mg tablet QD for up to 196 weeks; entospletinib 400 mg tablet QD orally for up to 196 weeks and single dose of obinutuzumab 1000 mg IV for up to 22 weeks. All drugs were administered for 28-day cycles.	7
Group V Single Agent Tirabrutinib Participants received tirabrutinib 80 mg tablet QD orally, for each 28-day cycle up to 194 weeks.	29
Group VI Single Agent Tirabrutinib: CLL Participants with CLL received tirabrutinib, at the original dose (20 - 160 mg), tablet QD, for each 28-day cycle up to 441 weeks.	3
Group VI Single Agent Tirabrutinib: NHL Participants with NHL received tirabrutinib, at the original dose (20 - 160 mg), tablet QD, for each 28-day cycle up to 441 weeks.	3
Total	203

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009	FG010	FG011	FG012	FG013	FG014	FG015	FG016
Overall Study	Adverse Event	0	1	1	4	1	0	0	1	0	1	6	0	0	1	2	0	0
Overall Study	Death	0	0	0	3	0	1	0	0	0	0	3	0	0	1	2	0	1
Overall Study	Intercurrent Illness	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Overall Study	Investigator's Discretion	0	2	2	2	0	0	0	1	2	0	10	2	2	1	5	0	0
Overall Study	Progressive Disease	2	2	1	11	7	3	2	1	1	2	45	6	2	2	10	1	1
Overall Study	Protocol Violation	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Overall Study	Study Terminated by Sponsor	0	1	0	4	1	0	1	0	0	0	4	0	1	0	8	1	0
Overall Study	Transition to the MHRA's Special Scheme	0	2	0	1	0	0	0	1	0	0	4	0	0	0	1	1	1
Overall Study	Unacceptable Toxicity	0	0	0	0	0	0	0	0	0	0	1	0	1	1	1	0	0
Overall Study	Withdrew Consent	0	0	0	0	0	0	0	2	0	0	3	0	0	1	0	0	0

Baseline characteristics

Characteristic	Combination I (Tirabrutinib 20 mg QD+ Idelalisib 50 mg BID)	Combination I (Tirabrutinib 40 mg QD+ Idelalisib 50 mg BID)	Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID)	Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	Combination I (Tirabrutinib 160 mg QD+ Idelalisib 100 mg QD)	Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID)	Combination II (Tirabrutinib 40 mg QD+ Entospletinib 200 mg QD)	Combination II (Tirabrutinib 80 mg QD+ Entospletinib 200 mg QD)	Combination II (Tirabrutinib 150 mg QD+ Entospletinib 200 mg QD)	Combination III (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD+ Obinutuzumab 1000 mg)	Combination II (Tirabrutinib 40 mg QD+ Entospletinib 400 mg QD)	Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	Combination II (Tirabrutinib 160 mg QD+ Entospletinib 400 mg QD)	Combination IV (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD+Obinutuzumab 1000 mg)	Group V Single Agent Tirabrutinib	Group VI Single Agent Tirabrutinib: CLL	Group VI Single Agent Tirabrutinib: NHL	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	1 Participants	5 Participants	2 Participants	13 Participants	7 Participants	1 Participants	3 Participants	5 Participants	2 Participants	3 Participants	3 Participants	52 Participants	4 Participants	4 Participants	21 Participants	2 Participants	3 Participants	131 Participants
Age, Categorical Between 18 and 65 years	2 Participants	3 Participants	2 Participants	12 Participants	2 Participants	4 Participants	0 Participants	1 Participants	1 Participants	3 Participants	0 Participants	26 Participants	4 Participants	3 Participants	8 Participants	1 Participants	0 Participants	72 Participants
Age, Continuous	66 years STANDARD_DEVIATION 4.4	65 years STANDARD_DEVIATION 9.7	62 years STANDARD_DEVIATION 12	64 years STANDARD_DEVIATION 13.2	73 years STANDARD_DEVIATION 8.9	55 years STANDARD_DEVIATION 12.8	70 years STANDARD_DEVIATION 7	66 years STANDARD_DEVIATION 11.1	67 years STANDARD_DEVIATION 5.1	59 years STANDARD_DEVIATION 11.8	67 years STANDARD_DEVIATION 1.2	68 years STANDARD_DEVIATION 11.7	63 years STANDARD_DEVIATION 11.9	64 years STANDARD_DEVIATION 14.4	70 years STANDARD_DEVIATION 9.4	66 years STANDARD_DEVIATION 4	74 years STANDARD_DEVIATION 4.4	67 years STANDARD_DEVIATION 11.3
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants	8 Participants	4 Participants	23 Participants	7 Participants	4 Participants	3 Participants	6 Participants	2 Participants	4 Participants	3 Participants	51 Participants	7 Participants	1 Participants	23 Participants	2 Participants	3 Participants	154 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	1 Participants	2 Participants	1 Participants	0 Participants	0 Participants	1 Participants	2 Participants	0 Participants	27 Participants	1 Participants	6 Participants	6 Participants	1 Participants	0 Participants	48 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	1 Participants	1 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	6 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	6 Participants	6 Participants	1 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	30 Participants	3 Participants	6 Participants	8 Participants	0 Participants	0 Participants	62 Participants
Race (NIH/OMB) White	3 Participants	7 Participants	3 Participants	17 Participants	3 Participants	3 Participants	3 Participants	6 Participants	3 Participants	4 Participants	3 Participants	46 Participants	5 Participants	1 Participants	21 Participants	3 Participants	3 Participants	134 Participants
Region of Enrollment France	0 Participants	2 Participants	2 Participants	8 Participants	6 Participants	1 Participants	1 Participants	0 Participants	1 Participants	4 Participants	2 Participants	35 Participants	7 Participants	7 Participants	7 Participants	0 Participants	0 Participants	83 Participants
Region of Enrollment United Kingdom	0 Participants	4 Participants	2 Participants	13 Participants	2 Participants	2 Participants	0 Participants	4 Participants	2 Participants	0 Participants	1 Participants	35 Participants	1 Participants	0 Participants	12 Participants	2 Participants	3 Participants	83 Participants
Region of Enrollment United States	3 Participants	2 Participants	0 Participants	4 Participants	1 Participants	2 Participants	2 Participants	2 Participants	0 Participants	2 Participants	0 Participants	8 Participants	0 Participants	0 Participants	10 Participants	1 Participants	0 Participants	37 Participants
Sex: Female, Male Female	3 Participants	2 Participants	0 Participants	10 Participants	4 Participants	2 Participants	0 Participants	3 Participants	0 Participants	3 Participants	2 Participants	25 Participants	3 Participants	3 Participants	12 Participants	1 Participants	2 Participants	75 Participants
Sex: Female, Male Male	0 Participants	6 Participants	4 Participants	15 Participants	5 Participants	3 Participants	3 Participants	3 Participants	3 Participants	3 Participants	1 Participants	53 Participants	5 Participants	4 Participants	17 Participants	2 Participants	1 Participants	128 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk	EG013 affected / at risk	EG014 affected / at risk	EG015 affected / at risk	EG016 affected / at risk
deaths Total, all-cause mortality	0 / 3	2 / 8	1 / 4	6 / 25	1 / 9	2 / 5	0 / 3	0 / 6	0 / 3	0 / 3	8 / 78	2 / 8	1 / 6	1 / 7	3 / 29	0 / 3	1 / 3
other Total, other adverse events	3 / 3	8 / 8	4 / 4	24 / 25	9 / 9	5 / 5	3 / 3	6 / 6	3 / 3	3 / 3	73 / 78	5 / 8	6 / 6	7 / 7	29 / 29	3 / 3	3 / 3
serious Total, serious adverse events	2 / 3	3 / 8	2 / 4	13 / 25	2 / 9	4 / 5	3 / 3	4 / 6	1 / 3	1 / 3	36 / 78	2 / 8	4 / 6	7 / 7	10 / 29	1 / 3	1 / 3

Outcome results

Primary

Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL

ORR for Waldenstrom Macroglobulinemia(WM):CR+VGPR+PR+MPR. CR: Absence of serum monoclonal IgM protein; normal serum IgM level: complete resolution of extramedullary disease, morphologically normal bone marrow/aspirate and trephine biopsy. Very good partial response (VGPR):Detectable monoclonal IgM; ≥90% reduction in serum IgM; Complete resolution of extramedullary disease; No new signs/symptoms. PR: Monoclonal immunoglobulin M (IgM) protein is detectable ≥50% but \<90% reduction in serum IgM level from baseline; reduction of extramedullary disease; no new signs or symptoms of active disease. Minor response (MPR):Detectable monoclonal IgM; ≥25% but \<50% reduction in serum IgM; No progression of extramedullary disease; No new signs/symptoms. Clopper-Pearson method was used in analysis. Data is reported by disease type: WM; Follicular Lymphoma (FL);Mantle Cell Lymphoma (MCL);Small Lymphocytic Lymphoma (SLL);Marginal Zone Lymphoma (MZL);Diffuse Large B-Cell Lymphoma (DLBCL) as applicable.

Time frame: Week 12

Population: Participants in the Full Analysis Set with non-CLL type of Non-Hodgkin's Lymphoma (NHL), were analyzed. The Full Analysis Set included all enrolled participants who took at least 1 dose of study drug. Group V did not have any participants with non-CLL type of NHL, therefore, no data is reported for this arm.

Arm	Measure	Group	Value (NUMBER)
Combination I (Tirabrutinib 20 mg QD+ Idelalisib 50 mg BID)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: SLL	50.0 percentage of participants
Combination I (Tirabrutinib 40 mg QD+ Idelalisib 50 mg BID)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: MCL	0 percentage of participants
Combination I (Tirabrutinib 40 mg QD+ Idelalisib 50 mg BID)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: FL	0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: FL	0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: DLBCL	0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: MZL	100.0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: MZL	33.3 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: FL	20.0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: WM	100.0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: DLBCL	14.3 percentage of participants
Combination I (Tirabrutinib 160 mg QD+ Idelalisib 100 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: DLBCL	22.2 percentage of participants
Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: WM	0 percentage of participants
Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: FL	0 percentage of participants
Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: MZL	0 percentage of participants
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 200 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: SLL	0 percentage of participants
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 200 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: MCL	0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 200 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: DLBCL	0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 200 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: FL	50.0 percentage of participants
Combination II (Tirabrutinib 150 mg QD+ Entospletinib 200 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: FL	100.0 percentage of participants
Combination II (Tirabrutinib 150 mg QD+ Entospletinib 200 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: DLBCL	100.0 percentage of participants
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 400 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: MZL	0 percentage of participants
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 400 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: FL	0 percentage of participants
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 400 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: WM	0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: DLBCL	17.9 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: MZL	50.0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: WM	42.9 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: FL	18.2 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: MCL	60.0 percentage of participants
Combination II (Tirabrutinib 160 mg QD+ Entospletinib 400 mg QD)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: DLBCL	12.5 percentage of participants
Combination III (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD+ Obinutuzumab 1000 mg)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: MZL	100.0 percentage of participants
Combination III (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD+ Obinutuzumab 1000 mg)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: MCL	100.0 percentage of participants
Combination III (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD+ Obinutuzumab 1000 mg)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: FL	25.0 percentage of participants
Combination IV(Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD+Obinutuzumab 1000 mg)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: FL	40.0 percentage of participants
Combination IV(Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD+Obinutuzumab 1000 mg)	Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL	Disease Subtype: MZL	50.0 percentage of participants

Primary

ORR: Percentage of Participants With CR or PR in Participants With CLL at Week 24

ORR was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR). CR and PR are defined in outcome measure#2. Clopper-Pearson method was used in outcome measure analysis. Percentages were rounded off.

Time frame: Week 24

Population: Participants in the Full Analysis Set with CLL were analyzed. There were 5 arms in Combinations I and II that did not have participants with CLL type of NHL. Also, Combinations III and IV did not have any participants with CLL type of NHL, therefore, no data is reported for these arms.

Arm	Measure	Value (NUMBER)
Combination I (Tirabrutinib 20 mg QD+ Idelalisib 50 mg BID)	ORR: Percentage of Participants With CR or PR in Participants With CLL at Week 24	100.0 percentage of participants
Combination I (Tirabrutinib 40 mg QD+ Idelalisib 50 mg BID)	ORR: Percentage of Participants With CR or PR in Participants With CLL at Week 24	80.0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID)	ORR: Percentage of Participants With CR or PR in Participants With CLL at Week 24	100.0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	ORR: Percentage of Participants With CR or PR in Participants With CLL at Week 24	66.7 percentage of participants
Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID)	ORR: Percentage of Participants With CR or PR in Participants With CLL at Week 24	100.0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 200 mg QD)	ORR: Percentage of Participants With CR or PR in Participants With CLL at Week 24	66.7 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	ORR: Percentage of Participants With CR or PR in Participants With CLL at Week 24	28.6 percentage of participants
Group V Single Agent Tirabrutinib 80 mg	ORR: Percentage of Participants With CR or PR in Participants With CLL at Week 24	79.3 percentage of participants

Primary

Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)

An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. TEAEs were defined as an AE that onset in the period from the first dose of study treatment to 30 days after the last dose of study treatment. Percentages were rounded off.

Time frame: First dose up to last dose date (up to 441 weeks) plus 30 days

Population: The Safety Analysis Set included all participants who took at least 1 dose of any study drug.

Arm	Measure	Value (NUMBER)
Combination I (Tirabrutinib 20 mg QD+ Idelalisib 50 mg BID)	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	100.0 percentage of participants
Combination I (Tirabrutinib 40 mg QD+ Idelalisib 50 mg BID)	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	100.0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID)	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	100.0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	100.0 percentage of participants
Combination I (Tirabrutinib 160 mg QD+ Idelalisib 100 mg QD)	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	100.0 percentage of participants
Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID)	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	100.0 percentage of participants
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 200 mg QD)	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	100.0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 200 mg QD)	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	100.0 percentage of participants
Combination II (Tirabrutinib 150 mg QD+ Entospletinib 200 mg QD)	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	100.0 percentage of participants
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 400 mg QD)	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	100.0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	96.2 percentage of participants
Combination II (Tirabrutinib 160 mg QD+ Entospletinib 400 mg QD)	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	75.0 percentage of participants
Combination III (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD+ Obinutuzumab 1000 mg)	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	100.0 percentage of participants
Combination IV(Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD+Obinutuzumab 1000 mg)	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	100.0 percentage of participants
Group V Single Agent Tirabrutinib 80 mg	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	100.0 percentage of participants
Group VI Single Agent Tirabrutinib: CLL	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	100.0 percentage of participants
Group VI Single Agent Tirabrutinib: NHL	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	100.0 percentage of participants

Primary

Percentage of Participants With Dose Limiting Toxicities (DLTs)

A DLT was defined as a ≥ Grade 3 AE that was assessed as related to study drug that occurred during the 28-day DLT assessment period with protocol-defined allowed exceptions. Any treatment-emergent adverse event (TEAE) that was, in the opinion of the Clinical Trial Steering Committee, of potential clinical significance such that further dosing exposed participants to unacceptable risk, was considered a DLT.

Time frame: Up to 28 days

Population: The participants in the DLT Analysis Set with available data were analyzed. The DLT Analysis Set included all participants in the dose escalation, in Combination I, II, III, IV, who completed all treatment for at least 21 days within the first 28 days, or experienced a DLT prior to Day 28, inclusive.

Arm	Measure	Value (NUMBER)
Combination I (Tirabrutinib 20 mg QD+ Idelalisib 50 mg BID)	Percentage of Participants With Dose Limiting Toxicities (DLTs)	0 percentage of participants
Combination I (Tirabrutinib 40 mg QD+ Idelalisib 50 mg BID)	Percentage of Participants With Dose Limiting Toxicities (DLTs)	0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID)	Percentage of Participants With Dose Limiting Toxicities (DLTs)	0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	Percentage of Participants With Dose Limiting Toxicities (DLTs)	0 percentage of participants
Combination I (Tirabrutinib 160 mg QD+ Idelalisib 100 mg QD)	Percentage of Participants With Dose Limiting Toxicities (DLTs)	0 percentage of participants
Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID)	Percentage of Participants With Dose Limiting Toxicities (DLTs)	20 percentage of participants
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 200 mg QD)	Percentage of Participants With Dose Limiting Toxicities (DLTs)	0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 200 mg QD)	Percentage of Participants With Dose Limiting Toxicities (DLTs)	0 percentage of participants
Combination II (Tirabrutinib 150 mg QD+ Entospletinib 200 mg QD)	Percentage of Participants With Dose Limiting Toxicities (DLTs)	0 percentage of participants
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 400 mg QD)	Percentage of Participants With Dose Limiting Toxicities (DLTs)	0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	Percentage of Participants With Dose Limiting Toxicities (DLTs)	0 percentage of participants
Combination II (Tirabrutinib 160 mg QD+ Entospletinib 400 mg QD)	Percentage of Participants With Dose Limiting Toxicities (DLTs)	0 percentage of participants
Combination III (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD+ Obinutuzumab 1000 mg)	Percentage of Participants With Dose Limiting Toxicities (DLTs)	0 percentage of participants
Combination IV(Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD+Obinutuzumab 1000 mg)	Percentage of Participants With Dose Limiting Toxicities (DLTs)	0 percentage of participants

Secondary

Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase

DOR was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definite disease progression or death from any cause. CR and PR are defined in outcome measure# 2. PD is defined in outcome measure #6. KM estimates were used in outcome measure analysis. Data is reported by disease type: CLL; FL; MCL; MZL; SLL; WM; DLBCL

Time frame: Up to 281 weeks

Population: Participants in the Full Analysis Set with ORR were analyzed.

Arm	Measure	Group	Value (MEDIAN)
Combination I (Tirabrutinib 20 mg QD+ Idelalisib 50 mg BID)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: CLL	NA months
Combination I (Tirabrutinib 20 mg QD+ Idelalisib 50 mg BID)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: SLL	19.3 months
Combination I (Tirabrutinib 40 mg QD+ Idelalisib 50 mg BID)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: CLL	NA months
Combination I (Tirabrutinib 40 mg QD+ Idelalisib 50 mg BID)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: MCL	10.7 months
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: CLL	26.5 months
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: MZL	3.3 months
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: MZL	2.5 months
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: WM	NA months
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: FL	3.0 months
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: DLBCL	3.9 months
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: CLL	NA months
Combination I (Tirabrutinib 160 mg QD+ Idelalisib 100 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: DLBCL	NA months
Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: FL	13.8 months
Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: CLL	34.1 months
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 200 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: SLL	51.4 months
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 200 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: FL	NA months
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 200 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: CLL	NA months
Combination II (Tirabrutinib 150 mg QD+ Entospletinib 200 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: FL	16.6 months
Combination II (Tirabrutinib 150 mg QD+ Entospletinib 200 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: DLBCL	NA months
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 400 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: FL	6.3 months
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 400 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: WM	NA months
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: MCL	24.9 months
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: CLL	NA months
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: FL	17.3 months
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: MZL	NA months
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: WM	NA months
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: DLBCL	8.3 months
Combination II (Tirabrutinib 160 mg QD+ Entospletinib 400 mg QD)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: DLBCL	NA months
Combination III (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD+ Obinutuzumab 1000 mg)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: FL	NA months
Combination III (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD+ Obinutuzumab 1000 mg)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: MCL	2.8 months
Combination III (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD+ Obinutuzumab 1000 mg)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: MZL	8.2 months
Combination IV(Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD+Obinutuzumab 1000 mg)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: FL	NA months
Combination IV(Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD+Obinutuzumab 1000 mg)	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: MZL	NA months
Group V Single Agent Tirabrutinib 80 mg	Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase	Disease Subtype: CLL	NA months

Secondary

ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase

ORR for WM is CR + VGPR + PR + MPR. CR, PR, VGPR and MPR are defined in outcome measure#2. Clopper-Pearson method was used in outcome measure analysis. Percentages were rounded off. Data is reported by disease type: CLL ; FL; MCL; MZL; SLL; WM; DLBCL.

Time frame: Up to 281 weeks

Population: Participants in the Full Analysis Set were analyzed.

Arm	Measure	Group	Value (NUMBER)
Combination I (Tirabrutinib 20 mg QD+ Idelalisib 50 mg BID)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: SLL	50.0 percentage of participants
Combination I (Tirabrutinib 20 mg QD+ Idelalisib 50 mg BID)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: CLL	100.0 percentage of participants
Combination I (Tirabrutinib 40 mg QD+ Idelalisib 50 mg BID)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: CLL	100.0 percentage of participants
Combination I (Tirabrutinib 40 mg QD+ Idelalisib 50 mg BID)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: MCL	100.0 percentage of participants
Combination I (Tirabrutinib 40 mg QD+ Idelalisib 50 mg BID)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: FL	0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: DLBCL	0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: CLL	100.0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: FL	0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: MZL	100.0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: FL	20.0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: CLL	83.3 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: MZL	33.3 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: WM	100.0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: DLBCL	14.3 percentage of participants
Combination I (Tirabrutinib 160 mg QD+ Idelalisib 100 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: DLBCL	33.3 percentage of participants
Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: MZL	0 percentage of participants
Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: WM	0 percentage of participants
Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: FL	50.0 percentage of participants
Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: CLL	100.0 percentage of participants
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 200 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: SLL	100.0 percentage of participants
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 200 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: MCL	0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 200 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: DLBCL	0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 200 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: FL	50.0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 200 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: CLL	100.0 percentage of participants
Combination II (Tirabrutinib 150 mg QD+ Entospletinib 200 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: DLBCL	100.0 percentage of participants
Combination II (Tirabrutinib 150 mg QD+ Entospletinib 200 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: FL	100.0 percentage of participants
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 400 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: FL	100.0 percentage of participants
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 400 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: MZL	0 percentage of participants
Combination II (Tirabrutinib 40 mg QD+ Entospletinib 400 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: WM	100.0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: CLL	100.0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: MCL	70.0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: DLBCL	25.0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: MZL	50.0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: FL	36.4 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: WM	85.7 percentage of participants
Combination II (Tirabrutinib 160 mg QD+ Entospletinib 400 mg QD)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: DLBCL	12.5 percentage of participants
Combination III (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD+ Obinutuzumab 1000 mg)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: MZL	100.0 percentage of participants
Combination III (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD+ Obinutuzumab 1000 mg)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: MCL	100.0 percentage of participants
Combination III (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD+ Obinutuzumab 1000 mg)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: FL	75.0 percentage of participants
Combination IV(Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD+Obinutuzumab 1000 mg)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: FL	60.0 percentage of participants
Combination IV(Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD+Obinutuzumab 1000 mg)	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: MZL	50.0 percentage of participants
Group V Single Agent Tirabrutinib 80 mg	ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase	Disease Subtype: CLL	86.2 percentage of participants

Secondary

Percentage of Participants Who Achieved Minimal Residual Negative Disease (< 1 Leukemia Cell/10,000 Leukocytes) During the Dose Escalation Phase and Dose Expansion Phase in Participants With CLL

Achieving Minimal Residual Disease was defined as \< 1 leukemia cell/10,000 leukocytes (10-4) in participants who have also achieved a CR. CR is defined in outcome measure #2.

Time frame: Up to 281 weeks

Population: Participants in the All Enrolled Analysis Set with CLL were analyzed.

Arm	Measure	Value (NUMBER)
Combination I (Tirabrutinib 20 mg QD+ Idelalisib 50 mg BID)	Percentage of Participants Who Achieved Minimal Residual Negative Disease (< 1 Leukemia Cell/10,000 Leukocytes) During the Dose Escalation Phase and Dose Expansion Phase in Participants With CLL	0 percentage of participants
Combination I (Tirabrutinib 40 mg QD+ Idelalisib 50 mg BID)	Percentage of Participants Who Achieved Minimal Residual Negative Disease (< 1 Leukemia Cell/10,000 Leukocytes) During the Dose Escalation Phase and Dose Expansion Phase in Participants With CLL	40 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID)	Percentage of Participants Who Achieved Minimal Residual Negative Disease (< 1 Leukemia Cell/10,000 Leukocytes) During the Dose Escalation Phase and Dose Expansion Phase in Participants With CLL	0 percentage of participants
Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)	Percentage of Participants Who Achieved Minimal Residual Negative Disease (< 1 Leukemia Cell/10,000 Leukocytes) During the Dose Escalation Phase and Dose Expansion Phase in Participants With CLL	16.7 percentage of participants
Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID)	Percentage of Participants Who Achieved Minimal Residual Negative Disease (< 1 Leukemia Cell/10,000 Leukocytes) During the Dose Escalation Phase and Dose Expansion Phase in Participants With CLL	0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 200 mg QD)	Percentage of Participants Who Achieved Minimal Residual Negative Disease (< 1 Leukemia Cell/10,000 Leukocytes) During the Dose Escalation Phase and Dose Expansion Phase in Participants With CLL	0 percentage of participants
Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)	Percentage of Participants Who Achieved Minimal Residual Negative Disease (< 1 Leukemia Cell/10,000 Leukocytes) During the Dose Escalation Phase and Dose Expansion Phase in Participants With CLL	28.6 percentage of participants
Group V Single Agent Tirabrutinib 80 mg	Percentage of Participants Who Achieved Minimal Residual Negative Disease (< 1 Leukemia Cell/10,000 Leukocytes) During the Dose Escalation Phase and Dose Expansion Phase in Participants With CLL	20.7 percentage of participants

Secondary

Pharmacokinetic (PK) Parameter: AUCtau of Tirabrutinib 80 mg

AUCtau was defined as concentration of drug over time. Area under the concentration verses time curve over the dosing interval (AUctau). The data for AUCtau is reported for tirabrutinib 80 mg as monotherapy and in combination with idelalisib 50 mg and 100 mg and entospletinib 200 mg and 400 mg.