A Phase 1/2, Open-Label, Dose Escalation, Safety and Tolerability Study of INCB050465 and Itacitinib in Subjects With Previously Treated B-Cell Malignancies (CITADEL-101)

A Phase 1/2, Open-Label, Dose Escalation, Safety and Tolerability Study of INCB050465 and Iitacitinib in Subjects With Previously Treated B-Cell Malignancies (CITADEL-101)

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02018861

Enrollment

Registered

2013-12-23

Start date

2016-09-22

Completion date

2021-04-12

Last updated

2023-09-28

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

Open-label, dose-escalation study in subjects with previously treated B-cell malignancies to find maximum tolerated dose (MTD) or pharmacologic active dose of a PI3Kδ inhibitor, parsaclisib, as monotherapy and in combination with: itacitinib (INCB039110), a JAK1 inhibitor; rituximab; and rituximab, ifosfamide, carboplatin, and etoposide. Parsaclisib inhibits PI3Kδ, a protein involved in growth and survival of B-cell cancer cells.

Interventions

DRUGParsaclisib

DRUGItacitinib

DRUGRituximab

DRUGIfosfamide

DRUGCarboplatin

DRUGEtoposide

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Aged 18 years or older, with lymphoid malignancies of B-cell origin including: 1. Indolent / aggressive B-cell non-Hodgkin's lymphoma (NHL) * EXCLUDING: Burkitt's lymphoma and precursor B lymphoblastic leukemia/lymphoma * INCLUDING: any non-Hodgkin's B cell malignancy such as chronic lymphocytic leukemia (CLL) and rare non-Hodgkin's B- cell subtypes such as hairy cell leukemia, Waldenström macroglobulinemia (WM), mantle cell leukemia (MCL), and transformed NHL histologies 2. Hodgkin's lymphoma (HL) * Life expectancy of 12 weeks or longer * Subject must have received ≥ 1 prior treatment regimen(s) * The subject must not be a candidate for potentially curative therapy including hematopoietic stem cell transplantation, except where one of the standard therapy regimen combinations may be used prior to transplantation per standard medical practice

Exclusion criteria

* Has history of brain metastasis, spinal cord compression (unless treated, asymptomatic, and stable on most recent imaging and enrolling in expansion cohort), or lymphoma involving the central nervous system (CNS) * Has an Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 3 (≥ 2 during dose escalation) * Received allogeneic hematopoietic stem cell transplant within the last 6 months, or has active graft versus host disease (GVHD) following allogeneic transplant, or currently receiving immunosuppressive therapy following allogeneic transplant * Received autologous hematopoietic stem cell transplant within the last 3 months * Inadequate marrow reserve assessed by hematologic laboratory parameters * Inadequate renal or liver function * Known HIV infection, or hepatitis B virus (HBV) or hepatitis C virus (HCV) viremia or at risk for HBV reactivation

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Up to approximately 53 months (4.4 years)	An adverse event (AE) is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after a participant provides informed consent. Abnormal laboratory values or test results occurring after informed consent constitute AEs only if they induce clinical signs or symptoms, are considered clinically meaningful, require therapy (e.g., hematologic abnormality that requires transfusion), or require changes in the study drug(s). A TEAE is defined as an event that was reported for the first time, or the worsening of a pre-existing event, after the first dose of study drug.

Secondary

Measure	Time frame	Description
Part 2: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL	Up to approximately 44 months (3.7 years)	CR: (a) peripheral blood lymphocytes \<4 x 10\^9/L; (b) no significant lymphadenopathy and lymph nodes \<1.5 cm in longest diameter; (c) no splenomegaly/hepatomegaly; (d) no disease-related constitutional symptoms; (e) neutrophils ≥1.5 x 10\^9/L; (f) platelets ≥100 x 10\^9/L; (g) hemoglobin ≥11.0 g/dL (without transfusion); (h) minimal residual disease assessment; (i) normocellular marrow, with no CLL cells/no B-lymphoid nodules. PR (improvement in ≥2 Group A parameters and ≥1 Group B parameter if previously abnormal. If only 1 parameter of both Groups A and B was abnormal before therapy, only 1 needs to improve): Group A: (a) decrease of ≥50% (from Baseline) in lymph nodes, liver/spleen size, and circulating lymphocyte count; (b) any constitutional symptoms. Group B: (a) platelets ≥100 x 10\^9/L or increase ≥50% over Baseline; (b) ≥11 g/dL or increase ≥50% over Baseline; (c) presence of CLL cells or B-lymphoid nodules.
Part 6: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL	Up to approximately 4 months	CR: (a) peripheral blood lymphocytes \<4 x 10\^9/L; (b) no significant lymphadenopathy and lymph nodes \<1.5 cm in longest diameter; (c) no splenomegaly/hepatomegaly; (d) no disease-related constitutional symptoms; (e) neutrophils ≥1.5 x 10\^9/L; (f) platelets ≥100 x 10\^9/L; (g) hemoglobin ≥11.0 g/dL (without transfusion); (h) minimal residual disease assessment; (i) normocellular marrow, with no CLL cells/no B-lymphoid nodules. PR (improvement in ≥2 Group A parameters and ≥1 Group B parameter if previously abnormal. If only 1 parameter of both Groups A and B was abnormal before therapy, only 1 needs to improve): Group A: (a) decrease of ≥50% (from Baseline) in lymph nodes, liver/spleen size, and circulating lymphocyte count; (b) any constitutional symptoms. Group B: (a) platelets ≥100 x 10\^9/L or increase ≥50% over Baseline; (b) ≥11 g/dL or increase ≥50% over Baseline; (c) presence of CLL cells or B-lymphoid nodules.
Part 1: ORR Based on the VIth International Workshop on Waldenström Macroglobulinemia (WM) Response Assessment for Participants With WM	Up to approximately 53 months (4.4 years)	ORR: sum of participants achieving minor response (MR), PR, very good partial response (VGPR), and CR. CR: (a) no serum monoclonal IgM protein by immunofixation; (b) normal serum IgM level; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at Baseline (BL); (d) morphologically normal bone marrow aspirate and trephine biopsy. VGPR: (a) detectable monoclonal IgM protein; (b) ≥90% reduction in serum IgM level from BL; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. PR: (a) detectable monoclonal IgM protein; (b) ≥50% but \<90% reduction in serum IgM level from BL; (c) reduction in extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. MR: (a) detectable monoclonal IgM protein; (b) ≥25% but \<50% reduction in serum IgM level from BL; (d) no new signs/symptoms of active disease.
Part 2: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM	Up to approximately 44 months (3.7 years)	ORR: sum of participants achieving MR, PR, VGPR, and CR. CR: (a) no serum monoclonal IgM protein by immunofixation; (b) normal serum IgM level; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) morphologically normal bone marrow aspirate and trephine biopsy. VGPR: (a) detectable monoclonal IgM protein; (b) ≥90% reduction in serum IgM level from BL; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. PR: (a) detectable monoclonal IgM protein; (b) ≥50% but \<90% reduction in serum IgM level from BL; (c) reduction in extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. MR: (a) detectable monoclonal IgM protein; (b) ≥25% but \<50% reduction in serum IgM level from BL; (d) no new signs/symptoms of active disease.
Part 6: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM	Up to approximately 4 months	ORR: sum of participants achieving MR, PR, VGPR, and CR. CR: (a) no serum monoclonal IgM protein by immunofixation; (b) normal serum IgM level; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) morphologically normal bone marrow aspirate and trephine biopsy. VGPR: (a) detectable monoclonal IgM protein; (b) ≥90% reduction in serum IgM level from BL; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. PR: (a) detectable monoclonal IgM protein; (b) ≥50% but \<90% reduction in serum IgM level from BL; (c) reduction in extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. MR: (a) detectable monoclonal IgM protein; (b) ≥25% but \<50% reduction in serum IgM level from BL; (d) no new signs/symptoms of active disease.
Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Up to approximately 53 months (4.4 years)	CR, PET-CT: (a) complete metabolic response (MR); (b) lymph nodes and extralymphatic sites (LNs/ELSs): score 1, 2, or 3, with/without residual mass; (c) no new lesions (NNLs); (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by \> 50% in length beyond normal; (c) NNLs.
Part 2: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT	Up to approximately 44 months (3.7 years)	CR, PET-CT: (a) complete MR; (b) LNs/ELSs: score 1, 2, or 3, with/without residual mass; (c) NNLs; (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by \> 50% in length beyond normal; (c) NNLs.
Part 6: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT	Up to approximately 4 months	CR, PET-CT: (a) complete MR; (b) LNs/ELSs: score 1, 2, or 3, with/without residual mass; (c) NNLs; (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by \> 50% in length beyond normal; (c) NNLs.
Cmax of Itacitinib in Combination With Parsaclisib	Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose	Cmax is defined as the maximum observed plasma or serum concentration of itacitinib.
Tmax of Itacitinib in Combination With Parsaclisib	Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose	tmax is defined as the time to the maximum concentration of itacitinib.
Cmin of Itacitinib in Combination With Parsaclisib	Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose	Cmin is defined as the minimum observed plasma or serum concentration over the dose interval of itacitinib.
Part 1: Overall Response Rate (Percentage of Participants With Complete Response [CR] and Partial Response [PR]) Based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria for Chronic Lymphocytic Leukemia (CLL) for CLL Participants	Up to approximately 53 months (4.4 years)	CR: (a) peripheral blood lymphocytes \<4 x 10\^9/Liter (L); (b) no significant lymphadenopathy and lymph nodes \<1.5 centimeters (cm) in longest diameter; (c) no splenomegaly/hepatomegaly; (d) no disease-related constitutional symptoms; (e) neutrophils ≥1.5 x 10\^9/L; (f) platelets ≥100 x 10\^9/L; (g) hemoglobin ≥11.0 grams/deciliter (g/dL) (without transfusion); (h) minimal residual disease assessment; (i) normocellular marrow, with no CLL cells/no B-lymphoid nodules. PR (improvement in ≥2 Group A parameters and ≥1 Group B parameter if previously abnormal. If only 1 parameter of both Groups A and B was abnormal before therapy, only 1 needs to improve): Group A: (a) decrease of ≥50% (from Baseline) in lymph nodes, liver/spleen size, and circulating lymphocyte count; (b) any constitutional symptoms. Group B: (a) platelets ≥100 x 10\^9/L or increase ≥50% over Baseline; (b) hemoglobin ≥11 g/dL or increase ≥50% over Baseline; (c) presence of CLL cells or B-lymphoid nodules.
AUC0-τ of Itacitinib in Combination With Parsaclisib	Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose	AUC0-τ is defined as the area under the steady-state plasma or serum concentration-time curve over 1 dose interval (i.e., from hour 0 to 12 for once every 12 hours \[q12h\] administration or from hour 0 to 24 for once every 24 hours \[q24h\] administration) of itacitinib.
Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose	Cmax is defined as the maximum observed plasma or serum concentration of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.
Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose	tmax is defined as the time to the maximum concentration of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.
Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose	Cmin is defined as the minimum observed plasma or serum concentration over the dose interval of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.
Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose	AUC0-t is defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.
Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose	AUC0-τ is defined as the area under the steady-state plasma or serum concentration-time curve over 1 dose interval (i.e., from hour 0 to 12 for q12h administration or from hour 0 to 24 for q24h administration) of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.
Part 3: Cmax of Parsaclisib Monotherapy	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose	Cmax is defined as the maximum observed plasma or serum concentration of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.
Part 3: Tmax of Parsaclisib Monotherapy	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose	tmax is defined as the time to the maximum concentration of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.
Part 3: Cmin of Parsaclisib Monotherapy	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose	Cmin is defined as the minimum observed plasma or serum concentration over the dose interval of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.
Part 3: AUC0-t of Parsaclisib Monotherapy	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose	AUC0-t is defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.
Part 3: AUC0-τ of Parsaclisib Monotherapy	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose	AUC0-τ is defined as the area under the steady-state plasma or serum concentration-time curve over 1 dose interval (i.e., from hour 0 to 12 for once every 12 hours \[q12h\] administration or from hour 0 to 24 for once every 24 hours \[q24h\] administration) of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.
AUC0-t of Itacitinib in Combination With Parsaclisib	Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose	AUC0-t is defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of itacitinib.

Countries

United States

Participant flow

Recruitment details

This study was conducted at 13 study centers in the United States.

Pre-assignment details

This was a 4-part study. Part 1 parsaclisib monotherapy dose escalation determined the recommended dose(s) (RDs) to explore. Part 2 evaluated the combination of parsaclisib and itacitinib to determine the RDs. Part 3 expansion further evaluated the RDs of parsaclisib as monotherapy and in combination with itacitinib in disease cohorts. Part 6 consisted of a safety assessment of parsaclisib in combination with the chemotherapy regimen R-ICE (rituximab, ifosfamide, carboplatin, and etoposide).

Participants by arm

Arm	Count
Parsaclisib 5 mg QD Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	1
Parsaclisib 10 mg QD Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	3
Parsaclisib 15 mg QD Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	3
Parsaclisib 20 mg QD Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	34
Parsaclisib 30 mg QD Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	27
Parsaclisib 45 mg QD Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	4
Parsaclisib 20 mg + Itacitinib 300 mg Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	8
Parsaclisib 30 mg + Itacitinib 300 mg Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	3
Parsaclisib 15 mg QD + R-ICE Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 milligrams per meters squared (mg/m\^2) intravenously (IV) on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m\^2 IV on Day 3 of each cycle, carboplatin area under the curve (AUC) = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m\^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration.	4
Parsaclisib 20 mg QD + R-ICE Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 mg/m\^2 IV on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m\^2 IV on Day 3 of each cycle, carboplatin AUC = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m\^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration.	1
Total	88

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008
Parsaclisib + Itacitinib; 21-day Cycles	Disease Progression	0	0	0	0	0	0	5	2	0
Parsaclisib + Itacitinib; 21-day Cycles	Unknown or Not Reported	0	0	0	0	0	0	3	1	0
Parsaclisib Monotherapy: 21-day Cycles	Adverse Event	0	2	1	6	4	1	0	0	0
Parsaclisib Monotherapy: 21-day Cycles	Death	1	0	0	3	1	0	0	0	0
Parsaclisib Monotherapy: 21-day Cycles	Disease Progression	0	1	1	13	18	1	0	0	0
Parsaclisib Monotherapy: 21-day Cycles	Lost to Follow-up	0	0	1	1	0	0	0	0	0
Parsaclisib Monotherapy: 21-day Cycles	Non-compliance with Study Treatment	0	0	0	0	1	0	0	0	0
Parsaclisib Monotherapy: 21-day Cycles	Physician Decision	0	0	0	4	1	2	0	0	0
Parsaclisib Monotherapy: 21-day Cycles	Unknown or Not Reported	0	0	0	2	1	0	0	0	0
Parsaclisib Monotherapy: 21-day Cycles	Withdrawal by Subject	0	0	0	1	1	0	0	0	0
Parsaclisib + R-ICE; 21-day Cycles	Adverse Event	0	0	0	0	0	0	0	0	1
Parsaclisib + R-ICE; 21-day Cycles	Disease Progression	0	0	0	0	0	0	0	0	1
Parsaclisib + R-ICE; 21-day Cycles	Physician Decision	0	0	0	0	0	0	0	0	1

Baseline characteristics

Characteristic	Parsaclisib 5 mg QD	Parsaclisib 10 mg QD	Parsaclisib 15 mg QD	Parsaclisib 20 mg QD	Parsaclisib 30 mg QD	Parsaclisib 45 mg QD	Parsaclisib 20 mg + Itacitinib 300 mg	Parsaclisib 30 mg + Itacitinib 300 mg	Parsaclisib 15 mg QD + R-ICE	Parsaclisib 20 mg QD + R-ICE	Total
Age, Continuous	NA years	69.0 years STANDARD_DEVIATION 16.52	63.3 years STANDARD_DEVIATION 9.45	62.4 years STANDARD_DEVIATION 16.48	63.7 years STANDARD_DEVIATION 11.81	66.8 years STANDARD_DEVIATION 8.77	64.6 years STANDARD_DEVIATION 17.15	51.7 years STANDARD_DEVIATION 27.02	62.3 years STANDARD_DEVIATION 8.26	NA years	63.3 years STANDARD_DEVIATION 14.44
Race/Ethnicity, Customized Black or African American	NA participants	NA participants	NA participants	4 participants	4 participants	NA participants	NA participants	NA participants	NA participants	NA participants	9 participants
Race/Ethnicity, Customized Unknown or Not Reported	NA participants	NA participants	NA participants	5 participants	2 participants	NA participants	NA participants	NA participants	NA participants	NA participants	9 participants
Race/Ethnicity, Customized White	NA participants	NA participants	NA participants	25 participants	21 participants	NA participants	NA participants	NA participants	NA participants	NA participants	70 participants
Sex/Gender, Customized Female	NA participants	NA participants	NA participants	12 participants	14 participants	NA participants	NA participants	NA participants	NA participants	NA participants	38 participants
Sex/Gender, Customized Male	NA participants	NA participants	NA participants	22 participants	13 participants	NA participants	NA participants	NA participants	NA participants	NA participants	50 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
deaths Total, all-cause mortality	1 / 1	0 / 3	0 / 3	3 / 34	1 / 27	0 / 4	0 / 8	0 / 3	0 / 4	0 / 1	5 / 88
other Total, other adverse events	1 / 1	3 / 3	3 / 3	32 / 34	24 / 27	4 / 4	6 / 8	3 / 3	4 / 4	1 / 1	81 / 88
serious Total, serious adverse events	1 / 1	2 / 3	1 / 3	14 / 34	12 / 27	2 / 4	0 / 8	2 / 3	1 / 4	1 / 1	36 / 88

Outcome results

Primary

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

An adverse event (AE) is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after a participant provides informed consent. Abnormal laboratory values or test results occurring after informed consent constitute AEs only if they induce clinical signs or symptoms, are considered clinically meaningful, require therapy (e.g., hematologic abnormality that requires transfusion), or require changes in the study drug(s). A TEAE is defined as an event that was reported for the first time, or the worsening of a pre-existing event, after the first dose of study drug.

Time frame: Up to approximately 53 months (4.4 years)

Population: Safety Population: all participants enrolled in the study who received at least 1 dose of parsaclisib, itacitinib, rituximab, ifosfamide, carboplatin, and/or etoposide

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Parsaclisib 5 mg QD	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	1 Participants
Parsaclisib 10 mg QD	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	3 Participants
Parsaclisib 15 mg QD	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	3 Participants
Parsaclisib 20 mg QD	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	32 Participants
Parsaclisib 30 mg QD	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	25 Participants
Parsaclisib 45 mg QD	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	4 Participants
Parsaclisib 20 mg + Itacitinib 300 mg	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	6 Participants
Parsaclisib 30 mg + Itacitinib 300 mg	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	3 Participants
Parsaclisib 15 mg QD + R-ICE	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	4 Participants
Parsaclisib 20 mg QD + R-ICE	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	1 Participants

Secondary

AUC0-t of Itacitinib in Combination With Parsaclisib

AUC0-t is defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of itacitinib.

Time frame: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Population: PK/PD Population. Data from the parsaclisib 20 mg + itacitinib 300 mg and the parsaclisib 30 mg + itacitinib 300 mg arms were pooled for analysis because all participants received 300 mg itacitinib and there is no drug-drug interaction between parsaclisib and itacitinib to affect the PK of either drug.

Arm	Measure	Value (MEAN)	Dispersion
Parsaclisib 5 mg QD	AUC0-t of Itacitinib in Combination With Parsaclisib	6450 hours (hr)*nmol/L	Standard Deviation 3780

Secondary

AUC0-τ of Itacitinib in Combination With Parsaclisib

Time frame: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Arm	Measure	Value (MEAN)	Dispersion
Parsaclisib 5 mg QD	AUC0-τ of Itacitinib in Combination With Parsaclisib	6450 hr*nmol/L	Standard Deviation 13780

Secondary

Cmax of Itacitinib in Combination With Parsaclisib

Cmax is defined as the maximum observed plasma or serum concentration of itacitinib.

Time frame: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Population: Pharmacokinetic (PK)/Pharmacodynamics (PD) Population: participants in the ITT/Safety Population who had PK/PD data. Data from the parsaclisib 20 mg + itacitinib 300 mg and the parsaclisib 30 mg + itacitinib 300 mg arms were pooled for analysis because all participants received 300 mg itacitinib and there is no drug-drug interaction between parsaclisib and itacitinib to affect the PK of either drug.

Arm	Measure	Value (MEAN)	Dispersion
Parsaclisib 5 mg QD	Cmax of Itacitinib in Combination With Parsaclisib	887 nanomoles (nmol)	Standard Deviation 404

Secondary

Cmin of Itacitinib in Combination With Parsaclisib

Cmin is defined as the minimum observed plasma or serum concentration over the dose interval of itacitinib.

Time frame: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Arm	Measure	Value (MEAN)	Dispersion
Parsaclisib 5 mg QD	Cmin of Itacitinib in Combination With Parsaclisib	32.8 nmol	Standard Deviation 32.5

Secondary

Part 1: ORR Based on the VIth International Workshop on Waldenström Macroglobulinemia (WM) Response Assessment for Participants With WM

ORR: sum of participants achieving minor response (MR), PR, very good partial response (VGPR), and CR. CR: (a) no serum monoclonal IgM protein by immunofixation; (b) normal serum IgM level; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at Baseline (BL); (d) morphologically normal bone marrow aspirate and trephine biopsy. VGPR: (a) detectable monoclonal IgM protein; (b) ≥90% reduction in serum IgM level from BL; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. PR: (a) detectable monoclonal IgM protein; (b) ≥50% but \<90% reduction in serum IgM level from BL; (c) reduction in extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. MR: (a) detectable monoclonal IgM protein; (b) ≥25% but \<50% reduction in serum IgM level from BL; (d) no new signs/symptoms of active disease.

Time frame: Up to approximately 53 months (4.4 years)

Population: ITT Population: all participants with WM. Confidence intervals were calculated based on the exact method for binomial distributions.

Arm	Measure	Value (NUMBER)
Parsaclisib 20 mg QD	Part 1: ORR Based on the VIth International Workshop on Waldenström Macroglobulinemia (WM) Response Assessment for Participants With WM	100.0 percentage of participants

Secondary

Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT

CR, PET-CT: (a) complete metabolic response (MR); (b) lymph nodes and extralymphatic sites (LNs/ELSs): score 1, 2, or 3, with/without residual mass; (c) no new lesions (NNLs); (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by \> 50% in length beyond normal; (c) NNLs.

Time frame: Up to approximately 53 months (4.4 years)

Population: ITT Population: all participants with the indicated types of HL and NHL. Confidence intervals were calculated based on the exact method for binomial distributions.

Arm	Measure	Group	Value (NUMBER)
Parsaclisib 5 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Diffuse large B-cell lymphoma	0.0 percentage of participants
Parsaclisib 10 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Follicular lymphoma	100.0 percentage of participants
Parsaclisib 10 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Diffuse large B-cell lymphoma	0.0 percentage of participants
Parsaclisib 15 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Follicular lymphoma	100.0 percentage of participants
Parsaclisib 15 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Diffuse large B-cell lymphoma	50.0 percentage of participants
Parsaclisib 20 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Classical Hodgkin's lymphoma	50.0 percentage of participants
Parsaclisib 20 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Follicular lymphoma	85.7 percentage of participants
Parsaclisib 20 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Mantle cell lymphoma	66.7 percentage of participants
Parsaclisib 20 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Splenic marginal zone lymphoma	100.0 percentage of participants
Parsaclisib 20 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Diffuse large B-cell lymphoma	36.4 percentage of participants
Parsaclisib 20 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Extranodal marginal zone lymphoma of mucosa-associated lymphatic tissue	50.0 percentage of participants
Parsaclisib 20 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Nodal marginal zone B-cell lymphoma	100.0 percentage of participants
Parsaclisib 30 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Classical Hodgkin's lymphoma	0.0 percentage of participants
Parsaclisib 30 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Diffuse large B-cell lymphoma	16.7 percentage of participants
Parsaclisib 30 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Follicular lymphoma	40.0 percentage of participants
Parsaclisib 30 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Mantle cell lymphoma	100.0 percentage of participants
Parsaclisib 30 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Marginal zone lymphoma	0.0 percentage of participants
Parsaclisib 30 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Nodal marginal zone B-cell lymphoma	100.0 percentage of participants
Parsaclisib 30 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Splenic marginal zone lymphoma	100.0 percentage of participants
Parsaclisib 30 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Nodular lymphocytic-predominant Hodgkin's lymphoma	0.0 percentage of participants
Parsaclisib 45 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Mantle cell lymphoma	0.0 percentage of participants
Parsaclisib 45 mg QD	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT	Diffuse large B-cell lymphoma	50.0 percentage of participants

Secondary

Part 1: Overall Response Rate (Percentage of Participants With Complete Response [CR] and Partial Response [PR]) Based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria for Chronic Lymphocytic Leukemia (CLL) for CLL Participants

CR: (a) peripheral blood lymphocytes \<4 x 10\^9/Liter (L); (b) no significant lymphadenopathy and lymph nodes \<1.5 centimeters (cm) in longest diameter; (c) no splenomegaly/hepatomegaly; (d) no disease-related constitutional symptoms; (e) neutrophils ≥1.5 x 10\^9/L; (f) platelets ≥100 x 10\^9/L; (g) hemoglobin ≥11.0 grams/deciliter (g/dL) (without transfusion); (h) minimal residual disease assessment; (i) normocellular marrow, with no CLL cells/no B-lymphoid nodules. PR (improvement in ≥2 Group A parameters and ≥1 Group B parameter if previously abnormal. If only 1 parameter of both Groups A and B was abnormal before therapy, only 1 needs to improve): Group A: (a) decrease of ≥50% (from Baseline) in lymph nodes, liver/spleen size, and circulating lymphocyte count; (b) any constitutional symptoms. Group B: (a) platelets ≥100 x 10\^9/L or increase ≥50% over Baseline; (b) hemoglobin ≥11 g/dL or increase ≥50% over Baseline; (c) presence of CLL cells or B-lymphoid nodules.

Time frame: Up to approximately 53 months (4.4 years)

Population: Intent-to-Treat (ITT) Population: all participants with CLL enrolled in the study who received at least 1 dose of parsaclisib, itacitinib, rituximab, ifosfamide, carboplatin, and/or etoposide. Confidence intervals were calculated based on the exact method for binomial distributions.

Arm	Measure	Value (NUMBER)
Parsaclisib 10 mg QD	Part 1: Overall Response Rate (Percentage of Participants With Complete Response [CR] and Partial Response [PR]) Based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria for Chronic Lymphocytic Leukemia (CLL) for CLL Participants	0.0 percentage of participants
Parsaclisib 20 mg QD	Part 1: Overall Response Rate (Percentage of Participants With Complete Response [CR] and Partial Response [PR]) Based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria for Chronic Lymphocytic Leukemia (CLL) for CLL Participants	0.0 percentage of participants
Parsaclisib 30 mg QD	Part 1: Overall Response Rate (Percentage of Participants With Complete Response [CR] and Partial Response [PR]) Based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria for Chronic Lymphocytic Leukemia (CLL) for CLL Participants	66.7 percentage of participants
Parsaclisib 45 mg QD	Part 1: Overall Response Rate (Percentage of Participants With Complete Response [CR] and Partial Response [PR]) Based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria for Chronic Lymphocytic Leukemia (CLL) for CLL Participants	0.0 percentage of participants

Secondary

Part 2: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM

ORR: sum of participants achieving MR, PR, VGPR, and CR. CR: (a) no serum monoclonal IgM protein by immunofixation; (b) normal serum IgM level; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) morphologically normal bone marrow aspirate and trephine biopsy. VGPR: (a) detectable monoclonal IgM protein; (b) ≥90% reduction in serum IgM level from BL; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. PR: (a) detectable monoclonal IgM protein; (b) ≥50% but \<90% reduction in serum IgM level from BL; (c) reduction in extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. MR: (a) detectable monoclonal IgM protein; (b) ≥25% but \<50% reduction in serum IgM level from BL; (d) no new signs/symptoms of active disease.

Time frame: Up to approximately 44 months (3.7 years)

Population: ITT Population: all participants with WM. Confidence intervals were calculated based on the exact method for binomial distributions.

Secondary

Part 2: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT

CR, PET-CT: (a) complete MR; (b) LNs/ELSs: score 1, 2, or 3, with/without residual mass; (c) NNLs; (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by \> 50% in length beyond normal; (c) NNLs.

Time frame: Up to approximately 44 months (3.7 years)

Population: ITT Population: all participants with the indicated types of HL and NHL. Confidence intervals were calculated based on the exact method for binomial distributions.

Arm	Measure	Group	Value (NUMBER)
Parsaclisib 5 mg QD	Part 2: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT	Diffuse large B-cell lymphoma	0.0 percentage of participants
Parsaclisib 5 mg QD	Part 2: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT	Follicular lymphoma	0.0 percentage of participants
Parsaclisib 5 mg QD	Part 2: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT	Mantle cell lymphoma	100.0 percentage of participants
Parsaclisib 5 mg QD	Part 2: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT	Classical Hodgkin's lymphoma	50.0 percentage of participants
Parsaclisib 10 mg QD	Part 2: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT	Diffuse large B-cell lymphoma	0.0 percentage of participants

Secondary

Part 2: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL

CR: (a) peripheral blood lymphocytes \<4 x 10\^9/L; (b) no significant lymphadenopathy and lymph nodes \<1.5 cm in longest diameter; (c) no splenomegaly/hepatomegaly; (d) no disease-related constitutional symptoms; (e) neutrophils ≥1.5 x 10\^9/L; (f) platelets ≥100 x 10\^9/L; (g) hemoglobin ≥11.0 g/dL (without transfusion); (h) minimal residual disease assessment; (i) normocellular marrow, with no CLL cells/no B-lymphoid nodules. PR (improvement in ≥2 Group A parameters and ≥1 Group B parameter if previously abnormal. If only 1 parameter of both Groups A and B was abnormal before therapy, only 1 needs to improve): Group A: (a) decrease of ≥50% (from Baseline) in lymph nodes, liver/spleen size, and circulating lymphocyte count; (b) any constitutional symptoms. Group B: (a) platelets ≥100 x 10\^9/L or increase ≥50% over Baseline; (b) ≥11 g/dL or increase ≥50% over Baseline; (c) presence of CLL cells or B-lymphoid nodules.

Time frame: Up to approximately 44 months (3.7 years)

Population: ITT Population: all participants with CLL. Confidence intervals were calculated based on the exact method for binomial distributions.

Arm	Measure	Value (NUMBER)
Parsaclisib 5 mg QD	Part 2: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL	100.0 percentage of participants

Secondary

Part 3: AUC0-t of Parsaclisib Monotherapy

AUC0-t is defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.

Time frame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Population: PK/PD Population. Only participants with available data were analyzed.

Arm	Measure	Group	Value (MEAN)	Dispersion
Parsaclisib 20 mg QD	Part 3: AUC0-t of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort A	6530 hr*nmol/L	Standard Deviation 2280
Parsaclisib 20 mg QD	Part 3: AUC0-t of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort B	7010 hr*nmol/L	—
Parsaclisib 20 mg QD	Part 3: AUC0-t of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort C	7110 hr*nmol/L	Standard Deviation 2760
Parsaclisib 20 mg QD	Part 3: AUC0-t of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort D	7230 hr*nmol/L	Standard Deviation 2530
Parsaclisib 30 mg QD	Part 3: AUC0-t of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort D	9970 hr*nmol/L	Standard Deviation 1260
Parsaclisib 30 mg QD	Part 3: AUC0-t of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort A	10700 hr*nmol/L	Standard Deviation 4150
Parsaclisib 30 mg QD	Part 3: AUC0-t of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort C	12000 hr*nmol/L	Standard Deviation 3230
Parsaclisib 30 mg QD	Part 3: AUC0-t of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort B	8430 hr*nmol/L	Standard Deviation 3560

Secondary

Part 3: AUC0-τ of Parsaclisib Monotherapy

AUC0-τ is defined as the area under the steady-state plasma or serum concentration-time curve over 1 dose interval (i.e., from hour 0 to 12 for once every 12 hours \[q12h\] administration or from hour 0 to 24 for once every 24 hours \[q24h\] administration) of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.

Time frame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Population: PK/PD Population. Only participants with available data were analyzed.

Arm	Measure	Group	Value (MEAN)	Dispersion
Parsaclisib 20 mg QD	Part 3: AUC0-τ of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort A	12600 hr*nmol/L	Standard Deviation 5170
Parsaclisib 20 mg QD	Part 3: AUC0-τ of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort D	13600 hr*nmol/L	Standard Deviation 7270
Parsaclisib 20 mg QD	Part 3: AUC0-τ of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort C	14200 hr*nmol/L	Standard Deviation 4600
Parsaclisib 20 mg QD	Part 3: AUC0-τ of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort B	17900 hr*nmol/L	—
Parsaclisib 30 mg QD	Part 3: AUC0-τ of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort D	25200 hr*nmol/L	Standard Deviation 8820
Parsaclisib 30 mg QD	Part 3: AUC0-τ of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort A	19500 hr*nmol/L	Standard Deviation 6020
Parsaclisib 30 mg QD	Part 3: AUC0-τ of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort B	20100 hr*nmol/L	Standard Deviation 6640
Parsaclisib 30 mg QD	Part 3: AUC0-τ of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort C	28000 hr*nmol/L	Standard Deviation 4310
Unknown	Part 3: AUC0-τ of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort C	— hr*nmol/L	—
Unknown	Part 3: AUC0-τ of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort A	— hr*nmol/L	—
Unknown	Part 3: AUC0-τ of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort D	— hr*nmol/L	—
Unknown	Part 3: AUC0-τ of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort B	— hr*nmol/L	—

Secondary

Part 3: Cmax of Parsaclisib Monotherapy

Cmax is defined as the maximum observed plasma or serum concentration of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.

Time frame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Population: PK/PD Population. Only participants with available data were analyzed.

Arm	Measure	Group	Value (MEAN)	Dispersion
Parsaclisib 20 mg QD	Part 3: Cmax of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort A	1550 nmol	Standard Deviation 544
Parsaclisib 20 mg QD	Part 3: Cmax of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort A	1720 nmol	Standard Deviation 492
Parsaclisib 20 mg QD	Part 3: Cmax of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort B	1200 nmol	—
Parsaclisib 20 mg QD	Part 3: Cmax of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort B	1930 nmol	—
Parsaclisib 20 mg QD	Part 3: Cmax of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort C	1760 nmol	Standard Deviation 772
Parsaclisib 20 mg QD	Part 3: Cmax of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort C	2060 nmol	Standard Deviation 682
Parsaclisib 20 mg QD	Part 3: Cmax of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort D	1760 nmol	Standard Deviation 580
Parsaclisib 20 mg QD	Part 3: Cmax of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort D	1600 nmol	Standard Deviation 378
Parsaclisib 30 mg QD	Part 3: Cmax of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort D	2990 nmol	Standard Deviation 783
Parsaclisib 30 mg QD	Part 3: Cmax of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort A	2350 nmol	Standard Deviation 944
Parsaclisib 30 mg QD	Part 3: Cmax of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort C	1760 nmol	Standard Deviation 534
Parsaclisib 30 mg QD	Part 3: Cmax of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort A	2390 nmol	Standard Deviation 648
Parsaclisib 30 mg QD	Part 3: Cmax of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort D	2500 nmol	Standard Deviation 279
Parsaclisib 30 mg QD	Part 3: Cmax of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort B	1720 nmol	Standard Deviation 925
Parsaclisib 30 mg QD	Part 3: Cmax of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort C	3920 nmol	Standard Deviation 1320
Parsaclisib 30 mg QD	Part 3: Cmax of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort B	2260 nmol	Standard Deviation 784

Secondary

Part 3: Cmin of Parsaclisib Monotherapy

Cmin is defined as the minimum observed plasma or serum concentration over the dose interval of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.

Time frame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Population: PK/PD Population. Only participants with available data were analyzed.

Arm	Measure	Group	Value (MEAN)	Dispersion
Parsaclisib 20 mg QD	Part 3: Cmin of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort A	214 nmol	Standard Deviation 171
Parsaclisib 20 mg QD	Part 3: Cmin of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort D	202 nmol	Standard Deviation 161
Parsaclisib 20 mg QD	Part 3: Cmin of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort C	197 nmol	Standard Deviation 79.6
Parsaclisib 20 mg QD	Part 3: Cmin of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort B	395 nmol	—
Parsaclisib 30 mg QD	Part 3: Cmin of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort D	421 nmol	Standard Deviation 365
Parsaclisib 30 mg QD	Part 3: Cmin of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort A	281 nmol	Standard Deviation 137
Parsaclisib 30 mg QD	Part 3: Cmin of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort B	296 nmol	Standard Deviation 177
Parsaclisib 30 mg QD	Part 3: Cmin of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort C	477 nmol	Standard Deviation 137
Unknown	Part 3: Cmin of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort C	— nmol	—
Unknown	Part 3: Cmin of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort A	— nmol	—
Unknown	Part 3: Cmin of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort D	— nmol	—
Unknown	Part 3: Cmin of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort B	— nmol	—

Secondary

Part 3: Tmax of Parsaclisib Monotherapy

tmax is defined as the time to the maximum concentration of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.

Time frame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Population: PK/PD Population. Only participants with available data were analyzed.

Arm	Measure	Group	Value (MEDIAN)
Parsaclisib 20 mg QD	Part 3: Tmax of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort A	0.5 hours
Parsaclisib 20 mg QD	Part 3: Tmax of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort C	0.5 hours
Parsaclisib 20 mg QD	Part 3: Tmax of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort B	2.0 hours
Parsaclisib 20 mg QD	Part 3: Tmax of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort C	1.0 hours
Parsaclisib 20 mg QD	Part 3: Tmax of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort D	1.0 hours
Parsaclisib 20 mg QD	Part 3: Tmax of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort A	1.0 hours
Parsaclisib 20 mg QD	Part 3: Tmax of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort D	0.5 hours
Parsaclisib 20 mg QD	Part 3: Tmax of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort B	0.5 hours
Parsaclisib 30 mg QD	Part 3: Tmax of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort D	1.0 hours
Parsaclisib 30 mg QD	Part 3: Tmax of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort A	1.0 hours
Parsaclisib 30 mg QD	Part 3: Tmax of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort A	1.0 hours
Parsaclisib 30 mg QD	Part 3: Tmax of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort B	1.5 hours
Parsaclisib 30 mg QD	Part 3: Tmax of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort B	0.75 hours
Parsaclisib 30 mg QD	Part 3: Tmax of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort C	1.0 hours
Parsaclisib 30 mg QD	Part 3: Tmax of Parsaclisib Monotherapy	Cycle 1 Day 1, Cohort D	0.75 hours
Parsaclisib 30 mg QD	Part 3: Tmax of Parsaclisib Monotherapy	Cycle 1 Day 15, Cohort C	0.5 hours

Secondary

Part 6: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM

Time frame: Up to approximately 4 months

Population: ITT Population: all participants with WM

Secondary

Part 6: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT

Time frame: Up to approximately 4 months

Population: ITT Population: all participants with the indicated types of HL and NHL

Arm	Measure	Group	Value (NUMBER)
Parsaclisib 5 mg QD	Part 6: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT	Diffuse large B-cell lymphoma	50.0 percentage of participants
Parsaclisib 10 mg QD	Part 6: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT	Diffuse large B-cell lymphoma	100.0 percentage of participants

Secondary

Part 6: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL

Time frame: Up to approximately 4 months

Population: ITT Population: all participants with CLL

Secondary

Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib

AUC0-t is defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.

Time frame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Population: PK/PD Population. Only participants with available data were analyzed. In the combination therapy arms, data are reported for the Part 3 Cohort E population (participants with B-cell malignancies).

Arm	Measure	Group	Value (MEAN)	Dispersion
Parsaclisib 5 mg QD	Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	2110 hr*nmol/L	—
Parsaclisib 10 mg QD	Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	3260 hr*nmol/L	Standard Deviation 1460
Parsaclisib 15 mg QD	Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	3730 hr*nmol/L	Standard Deviation 678
Parsaclisib 20 mg QD	Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	5990 hr*nmol/L	Standard Deviation 2650
Parsaclisib 30 mg QD	Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	13300 hr*nmol/L	Standard Deviation 2480
Parsaclisib 45 mg QD	Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	16800 hr*nmol/L	Standard Deviation 4880
Parsaclisib 20 mg + Itacitinib 300 mg	Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	7540 hr*nmol/L	Standard Deviation 3370
Parsaclisib 30 mg + Itacitinib 300 mg	Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	10400 hr*nmol/L	Standard Deviation 1330

Secondary

Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib

AUC0-τ is defined as the area under the steady-state plasma or serum concentration-time curve over 1 dose interval (i.e., from hour 0 to 12 for q12h administration or from hour 0 to 24 for q24h administration) of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.

Time frame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Arm	Measure	Group	Value (MEAN)	Dispersion
Parsaclisib 5 mg QD	Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	7130 hr*nmol/L	—
Parsaclisib 10 mg QD	Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	6910 hr*nmol/L	Standard Deviation 2330
Parsaclisib 15 mg QD	Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	11100 hr*nmol/L	Standard Deviation 6310
Parsaclisib 20 mg QD	Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	11900 hr*nmol/L	Standard Deviation 5110
Parsaclisib 30 mg QD	Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	24800 hr*nmol/L	Standard Deviation 2140
Parsaclisib 45 mg QD	Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	47700 hr*nmol/L	Standard Deviation 30500
Parsaclisib 20 mg + Itacitinib 300 mg	Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	22400 hr*nmol/L	Standard Deviation 17100
Parsaclisib 30 mg + Itacitinib 300 mg	Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	22900 hr*nmol/L	Standard Deviation 10700
Unknown	Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	— hr*nmol/L	—

Secondary

Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib

Cmax is defined as the maximum observed plasma or serum concentration of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.

Time frame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Arm	Measure	Group	Value (MEAN)	Dispersion
Parsaclisib 5 mg QD	Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	354 nmol	—
Parsaclisib 5 mg QD	Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	690 nmol	—
Parsaclisib 10 mg QD	Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	791 nmol	Standard Deviation 502
Parsaclisib 10 mg QD	Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	856 nmol	Standard Deviation 449
Parsaclisib 15 mg QD	Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	808 nmol	Standard Deviation 316
Parsaclisib 15 mg QD	Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	1310 nmol	Standard Deviation 290
Parsaclisib 20 mg QD	Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	1270 nmol	Standard Deviation 655
Parsaclisib 20 mg QD	Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	1280 nmol	Standard Deviation 437
Parsaclisib 30 mg QD	Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	3270 nmol	Standard Deviation 775
Parsaclisib 30 mg QD	Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	3310 nmol	Standard Deviation 682
Parsaclisib 45 mg QD	Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	4010 nmol	Standard Deviation 1400
Parsaclisib 45 mg QD	Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	5530 nmol	Standard Deviation 3210
Parsaclisib 20 mg + Itacitinib 300 mg	Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	2390 nmol	Standard Deviation 1480
Parsaclisib 20 mg + Itacitinib 300 mg	Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	1740 nmol	Standard Deviation 1010
Parsaclisib 30 mg + Itacitinib 300 mg	Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	2040 nmol	Standard Deviation 338
Parsaclisib 30 mg + Itacitinib 300 mg	Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	2500 nmol	Standard Deviation 973

Secondary

Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib

Cmin is defined as the minimum observed plasma or serum concentration over the dose interval of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.

Time frame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Arm	Measure	Group	Value (MEAN)	Dispersion
Parsaclisib 5 mg QD	Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	127 nmol	—
Parsaclisib 10 mg QD	Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	104 nmol	Standard Deviation 46
Parsaclisib 15 mg QD	Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	156 nmol	Standard Deviation 99.8
Parsaclisib 20 mg QD	Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	178 nmol	Standard Deviation 141
Parsaclisib 30 mg QD	Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	295 nmol	Standard Deviation 83.1
Parsaclisib 45 mg QD	Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	864 nmol	Standard Deviation 690
Parsaclisib 20 mg + Itacitinib 300 mg	Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	515 nmol	Standard Deviation 652
Parsaclisib 30 mg + Itacitinib 300 mg	Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	341 nmol	Standard Deviation 278
Unknown	Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	— nmol	—

Secondary

Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib

tmax is defined as the time to the maximum concentration of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.

Time frame: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Arm	Measure	Group	Value (MEDIAN)
Parsaclisib 5 mg QD	Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	0.5 hours
Parsaclisib 5 mg QD	Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	2.0 hours
Parsaclisib 10 mg QD	Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	1.0 hours
Parsaclisib 10 mg QD	Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	1.0 hours
Parsaclisib 15 mg QD	Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	1.0 hours
Parsaclisib 15 mg QD	Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	1.0 hours
Parsaclisib 20 mg QD	Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	1.0 hours
Parsaclisib 20 mg QD	Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	1.0 hours
Parsaclisib 30 mg QD	Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	0.5 hours
Parsaclisib 30 mg QD	Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	0.5 hours
Parsaclisib 45 mg QD	Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	1.0 hours
Parsaclisib 45 mg QD	Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	0.5 hours
Parsaclisib 20 mg + Itacitinib 300 mg	Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	1.0 hours
Parsaclisib 20 mg + Itacitinib 300 mg	Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	1.0 hours
Parsaclisib 30 mg + Itacitinib 300 mg	Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 1	1.0 hours
Parsaclisib 30 mg + Itacitinib 300 mg	Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib	Cycle 1 Day 15	1.0 hours

Secondary

Tmax of Itacitinib in Combination With Parsaclisib

tmax is defined as the time to the maximum concentration of itacitinib.

Time frame: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Arm	Measure	Value (MEDIAN)
Parsaclisib 5 mg QD	Tmax of Itacitinib in Combination With Parsaclisib	2.0 hours

Source: ClinicalTrials.gov · Data processed: Feb 28, 2026

A Phase 1/2, Open-Label, Dose Escalation, Safety and Tolerability Study of INCB050465 and Itacitinib in Subjects With Previously Treated B-Cell Malignancies (CITADEL-101)

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

AUC0-t of Itacitinib in Combination With Parsaclisib

AUC0-τ of Itacitinib in Combination With Parsaclisib

Cmax of Itacitinib in Combination With Parsaclisib

Cmin of Itacitinib in Combination With Parsaclisib

Part 1: ORR Based on the VIth International Workshop on Waldenström Macroglobulinemia (WM) Response Assessment for Participants With WM

Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT

Part 1: Overall Response Rate (Percentage of Participants With Complete Response [CR] and Partial Response [PR]) Based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria for Chronic Lymphocytic Leukemia (CLL) for CLL Participants

Part 2: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM

Part 2: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT

Part 2: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL

Part 3: AUC0-t of Parsaclisib Monotherapy

Part 3: AUC0-τ of Parsaclisib Monotherapy

Part 3: Cmax of Parsaclisib Monotherapy

Part 3: Cmin of Parsaclisib Monotherapy

Part 3: Tmax of Parsaclisib Monotherapy

Part 6: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM

Part 6: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT

Part 6: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL

Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib

Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib

Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib

Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib

Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib

Tmax of Itacitinib in Combination With Parsaclisib