Platform Study of Novel Ruxolitinib Combinations in Myelofibrosis Patients

A Randomized, Open-label, Phase I/II Open Platform Study Evaluating Safety and Efficacy of Novel Ruxolitinib Combinations in Myelofibrosis Patients

Status

Terminated

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04097821

Acronym

ADORE

Enrollment

Registered

2019-09-20

Start date

2019-09-26

Completion date

2024-08-28

Last updated

2025-08-07

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

Conditions

Myelofibrosis

Keywords

myelofibrosis, ruxolitinib, INC424, siremadlin, HDM201, crizanlizumab, SEG101, sabatolimab, MBG453, rineterkib, LTT462, NIS793, platform study

Brief summary

The purpose of this study was to investigate the safety, pharmacokinetics and preliminary efficacy of combination treatment of ruxolitinib with 5 novel compounds: siremadlin, crizanlizumab, sabatolimab, rineterkib and NIS793 in myelofibrosis (MF) subjects.

Detailed description

This open-label, multi-center, Phase Ib/II platform study design consisted of 3 parts. Part 1 was a Phase Ib dose escalation and safety run-in for the 5 novel agents in combination with ruxolitinib to assess safety, tolerability and to confirm a recommended Phase II dose. Dose escalation cohorts were treated with ruxoltinib + siremadlin or ruxolitinib + rineterkib. Safety run-in cohorts were treated with either ruxolitinb + sabatolimab, ruxolitinb + crizanlizumab or ruxolitinib + NIS7913. Parts 2 and 3 were Phase II selection and expansion, respectively, to assess preliminary efficacy of the combination treatments from Part 1 that were evaluated as safe and tolerable. The number of combination treatment arms opening in Part 2 depended on the results of Part 1. In Part 2, an interim analysis was planned to determine if combination treatment(s) could be expanded in Part 3. In June 2022, Novartis decided to permanently halt the study enrollment in all ongoing parts (Part 1 and Part 2), and Part 3 (expansion) was not initiated. With Protocol Amendment 8, an extension treatment phase of 12 cycles was added in Part 1 to allow access to the combination treatment for ongoing subjects deriving clinical benefit. In consideration of the enrollment halt, Parts 2 and 3 objectives were not pursued, and Part 1 objectives were updated accordingly.

Interventions

DRUGRineterkib

100 mg capsule for oral use

DRUGNIS793

700 mg/7 mL concentrate for infusion for intravenous use

DRUGRuxolitinib

5 mg tablets for oral use

DRUGSiremadlin

10 mg, 20 mg, or 40 mg capsules for oral use

DRUGCrizanlizumab

100 mg/10 mL concentrate for infusion for intravenous use

DRUGSabatolimab

100 mg/mL or 400 mg/4 mL concentrate for infusion for intravenous use

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Masking description

Open label

Intervention model description

This open-label, multi-center, phase Ib/II platform study design consisted of 3 parts. Part 1 was a phase Ib dose escalation and safety run-in for the 5 novel agents in combination with ruxolitinib to assess safety, tolerability and to confirm recommended Phase II dose. Parts 2 and 3 were phase II selection and expansion respectively, to assess preliminary efficacy of the combination treatments from Part 1 that were evaluated as safe and tolerable. The number of combination treatment arms opening in Part 2 depended on the results of Part 1. In Part 2, interim analysis was planned to determine if combination treatment(s) could be expanded in Part 3.

Eligibility

Sex/Gender

ALL

Age

18 Years to 100 Years

Healthy volunteers

Inclusion criteria

Core treatment phase Inclusion Criteria: * Subjects have diagnosis of primary myelofibrosis (PMF) according to the 2016 World Health Organization (WHO) criteria, or diagnosis of post-essential thrombocythemia (ET) (PET-MF) or post-polycythemia vera (PV) myelofibrosis (PPV-MF) according to the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) 2007 criteria * Palpable spleen of at least 5 cm from the left costal margin (LCM) to the point of greatest splenic protrusion or enlarged spleen volume of at least 450 cm3 per MRI or CT scan at baseline (a MRI/CT scan up to 8 weeks prior to first dose of study treatment can be accepted). * Have been treated with ruxolitinib for at least 12 weeks prior to first dose of study treatment * Are stable (no dose adjustments) on the prescribed ruxolitinib dose (between 5 and 25 mg twice a day (BID)) for ≥ 4 weeks prior to first dose of study treatment Extension treatment phase inclusion criteria: * Signed consent for the extension treatment phase * ongoing in the core treatment phase * demonstrates clinical benefit of treatment in core treatment phase per investigator's assessment. Core treatment phase

Exclusion criteria

* Not able to understand and to comply with study instructions and requirements. * Received any investigational agent for the treatment of MF (except ruxolitinib) within 30 days of first dose of study treatment or within 5 half-lives of the study treatment, whichever is greater * Peripheral blood blasts count of \> 10%. * has documented severe hypersensitivity reactions/immunogenicity (IG) to a prior biologic product or Received a monoclonal antibody (Ab) or immunoglobulin-based agent within 1 year of screening in NIS793, crizanlizumab or sabatolimab arms, or in rineterkib or siremadlin arms within \<=4 weeks of screening or \<=5 half-lives whichever is shorter * Splenic irradiation within 6 months prior to the first dose of study drug * Received blood platelet transfusion within 28 days prior to first dose of study treatment. Extension treatment phase

Design outcomes

Primary

Measure	Time frame	Description
Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1	Baseline to the end of Cycle 2 (6 or 8 weeks)	Incidence and severity of dose limiting toxicities within the first 2 cycles (6 or 8 weeks) in Part 1 of the study. DLTs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) criteria Version 5.0. Grade 0 was assigned for all non-missing values not graded as 1 or higher. Higher grade indicated more severity. Grade 5 was not used.
Response Rate at the End of Cycle 6 or Cycle 8 in Part 1	Baseline to the end of Cycle 6 or 8 (24 weeks)	Composite of anemia improvement (hemoglobin level) and no spleen volume progression and no symptom worsening in Part 2 and Part 3 of the study. For a subject to be considered a responder, all three components of the composite had to be fulfilled.

Secondary

Measure	Time frame	Description
Change in Spleen Length From Baseline in Part 1	Baseline, Week 24, Week 48	Change in spleen length measured in centimeters by manual palpation.
Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1	Week 24, Week 48	Change in spleen volume measured by magnetic resonance imaging (MRI) or computed tomography (CT) from baseline.
Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1	Week 24, Week 48	Change in spleen volume measured by magnetic resonance imaging (MRI) or computed tomography (CT) from baseline.
Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 12, Week 24, Week 48	The MFSAF v4.0 questionnaire focuses on the 7 core symptoms of MF: fatigue, night sweats, pruritus, abdominal discomfort, pain under the ribs on the left side, early satiety and bone pain. Subjects record symptom severity at it worst for each of the 7 symptoms on an 11-point numeric rating scale, from 0 (absent) to 10 (worst imaginable). The Total Symptom Score (TSS) is the sum of all the scores for all 7 symptoms.
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Days 1 and 5 of Cycles 1 and 2 for siremadlin and Cycles 1 and 3 for crizanlizumab, sabatolimab, and NIS793; Days 1 and 15 of Cycle 1 for rineterkib	—
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Days 1 and 5 of Cycles 1 and 2; Day 15 of Cycle 1	—
Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Days 1 and 5 of Cycles 1 and 2 for siremadlin and Cycles 1 and 3 for crizanlizumab, sabatolimab, and NIS793; Days 1 and 15 of Cycle 1 for rineterkib	—
Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Days 1 and 5 of Cycles 1 and 2; Day 15 of Cycle 1	—
Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1	Week 24, Week 48	—
Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Days 1 and 5 of Cycles 1 and 2; Day 15 of Cycle 1	—
Concentration Versus Time Profile for Siremadlin in Part 1	Day 1 of Cycles 1 and 2; Day 6 of Cycle 1; Days 2 and 5 of Cycles 1, 2, 3, 4, 5, and 6. Each cycle was 28 days.	—
Concentration Versus Time Profile for Rineterkib in Part 1	Days 1, 2, 15, and 16 of Cycle 1; Day 1 of Cycles 2, 3, 4, 5, and 6. Each cycle was 28 days.	—
Concentration Versus Time Profile for Crizanlizumab in Part 1	Days 1, 2, 8, and 15 of Cycles 1, 2, and 3; Day 1 of Cycles 4, 5, 6, and 9. Each cycle was 28 days.	EOI = end of infusion
Concentration Versus Time Profile for Sabatolimab in Part 1	Days 1, 2, 8, and 15 of Cycles 1, 2, and 3; Day 1 of Cycles 4 and 5. Each cycle was 28 days.	EOI = end of infusion
Concentration Versus Time Profile for NIS793 in Part 1	Days 1, 2, 4, 8, 11, and 15 of Cycles 1, 2, and 3; Day 1 of Cycles 4 and 5. Each cycle was 28 days.	EOI = end of infusion
Concentration Versus Time Profile for Ruxolitinib in Part 1	Days 1, 2, 5, 6, and 15 of Cycles 1 and 2; Day 16 of Cycle 1; Days 1, 2, and 15 of Cycle 3; Days 1 and 5 of Cycles 4, 5, and 6. Each cycle was 28 days.	—
Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Days 1 and 5 of Cycles 1 and 2 for siremadlin and Cycles 1 and 3 for crizanlizumab, sabatolimab, and NIS793; Days 1 and 15 of Cycle 1 for rineterkib	—
Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1	Week 24, Week 48	—

Countries

Australia, Canada, Denmark, Germany, Hungary, Italy, Netherlands, Russia, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom

Participant flow

Pre-assignment details

All inclusion and exclusion criteria were checked at screening.

Participants by arm

Arm	Count
Part 1: Ruxolitinib + Siremadlin 20 mg Dose escalation of siremadlin added to existing stable dose of ruxolitinib	7
Part 1: Ruxolitinib + Siremadlin 30 mg Dose escalation of siremadlin added to existing stable dose of ruxolitinib	10
Part 1: Ruxolitinib + Siremadlin 40 mg Dose escalation of siremadlin added to existing stable dose of ruxolitinib	6
Part 1: Ruxolitinib + Rineterkib 200 mg Dose escalation of rineterkib added to existing stable dose of ruxolitinib	9
Part 1: Ruxolitinib + Crizanlizumab Safety run-in of crizanlizumab added to existing stable dose of ruxolitinib	6
Part 1: Ruxolitinib + Sabatolimab Safety run-in of sabatolimab added to existing stable dose of ruxolitinib	2
Part 1: Ruxolitinib + NIS793 Safety run-in of NIS793 added to existing stable dose of ruxolitinib	4
Part 2: Ruxolitinib Existing stable dose of ruxolitinib as control for Part 2	0
Total	44

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007
Overall Study	Adverse Event	0	0	1	1	0	0	0	0
Overall Study	Death	0	0	3	1	0	0	0	0
Overall Study	New Therapy For Study Indication	0	0	0	0	0	0	1	0
Overall Study	Physician Decision	1	2	0	0	0	0	0	0
Overall Study	Subject Decision	0	0	0	1	2	2	0	1

Baseline characteristics

Characteristic	Part 1: Ruxolitinib + Siremadlin 20 mg	Part 1: Ruxolitinib + Siremadlin 30 mg	Part 1: Ruxolitinib + Siremadlin 40 mg	Part 1: Ruxolitinib + Rineterkib 200 mg	Part 1: Ruxolitinib + Crizanlizumab	Part 1: Ruxolitinib + Sabatolimab	Part 1: Ruxolitinib + NIS793	Total
Age, Continuous	70.6 years STANDARD_DEVIATION 6.5	62.3 years STANDARD_DEVIATION 10.7	74.3 years STANDARD_DEVIATION 9.9	67.3 years STANDARD_DEVIATION 7.8	65.0 years STANDARD_DEVIATION 8.1	62.5 years STANDARD_DEVIATION 12	70.8 years STANDARD_DEVIATION 7.3	67.4 years STANDARD_DEVIATION 9.2
Age, Customized <65	1 Participants	5 Participants	1 Participants	4 Participants	4 Participants	1 Participants	1 Participants	17 Participants
Age, Customized >=65	6 Participants	5 Participants	5 Participants	5 Participants	2 Participants	1 Participants	3 Participants	27 Participants
Race/Ethnicity, Customized Unknown	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	2 Participants
Race/Ethnicity, Customized White	7 Participants	10 Participants	6 Participants	8 Participants	5 Participants	2 Participants	4 Participants	42 Participants
Sex: Female, Male Female	2 Participants	6 Participants	0 Participants	2 Participants	1 Participants	0 Participants	1 Participants	12 Participants
Sex: Female, Male Male	5 Participants	4 Participants	6 Participants	7 Participants	5 Participants	2 Participants	3 Participants	32 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
deaths Total, all-cause mortality	0 / 7	0 / 10	3 / 6	3 / 23	1 / 9	0 / 6	0 / 2	0 / 4	0 / 1	4 / 45
other Total, other adverse events	7 / 7	10 / 10	6 / 6	23 / 23	9 / 9	6 / 6	2 / 2	3 / 4	0 / 1	43 / 45
serious Total, serious adverse events	2 / 7	3 / 10	4 / 6	9 / 23	3 / 9	1 / 6	1 / 2	1 / 4	0 / 1	15 / 45

Outcome results

Primary

Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1

Incidence and severity of dose limiting toxicities within the first 2 cycles (6 or 8 weeks) in Part 1 of the study. DLTs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) criteria Version 5.0. Grade 0 was assigned for all non-missing values not graded as 1 or higher. Higher grade indicated more severity. Grade 5 was not used.

Time frame: Baseline to the end of Cycle 2 (6 or 8 weeks)

Population: The dose-determining set included all subjects from the safety run-in and dose escalation part (Part 1) of the study who met the minimum exposure criterion and had sufficient safety evaluations or experienced a DLT between C1D1 and C3D1. Number analyzed is the number of participants with available data.

Arm	Measure	Group	Value (NUMBER)
Part 1: Ruxolitinib + Siremadlin 20 mg	Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1	Grade 3	0 participants
Part 1: Ruxolitinib + Siremadlin 20 mg	Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1	Grade 4	0 participants
Part 1: Ruxolitinib + Siremadlin 30 mg	Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1	Grade 3	0 participants
Part 1: Ruxolitinib + Siremadlin 30 mg	Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1	Grade 4	1 participants
Part 1: Ruxolitinib + Siremadlin 40 mg	Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1	Grade 3	1 participants
Part 1: Ruxolitinib + Siremadlin 40 mg	Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1	Grade 4	1 participants
Part 1: Ruxolitinib + Rineterkib 200 mg	Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1	Grade 3	1 participants
Part 1: Ruxolitinib + Rineterkib 200 mg	Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1	Grade 4	0 participants
Part 1: Ruxolitinib + Crizanlizumab	Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1	Grade 3	0 participants
Part 1: Ruxolitinib + Crizanlizumab	Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1	Grade 4	0 participants
Part 1: Ruxolitinib + Sabatolimab	Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1	Grade 3	0 participants
Part 1: Ruxolitinib + Sabatolimab	Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1	Grade 4	0 participants

Primary

Response Rate at the End of Cycle 6 or Cycle 8 in Part 1

Composite of anemia improvement (hemoglobin level) and no spleen volume progression and no symptom worsening in Part 2 and Part 3 of the study. For a subject to be considered a responder, all three components of the composite had to be fulfilled.

Time frame: Baseline to the end of Cycle 6 or 8 (24 weeks)

Population: Enrollment was permanently halted; therefore, data were not collected for this outcome measure.

Secondary

Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1

Time frame: Days 1 and 5 of Cycles 1 and 2; Day 15 of Cycle 1

Population: The pharmacokinetic (PK) analysis set included all enrolled subjects who had an evaluable PK profile.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1: Ruxolitinib + Siremadlin 20 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2	1090 ng*hr/mL	—
Part 1: Ruxolitinib + Siremadlin 20 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	546 ng*hr/mL	Standard Deviation 412
Part 1: Ruxolitinib + Siremadlin 20 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 2 Day 1 n=2,2,1,0,0,0,0	354 ng*hr/mL	Standard Deviation 101
Part 1: Ruxolitinib + Siremadlin 20 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 2 Day 1 n=3,3,1,0,0,0,0	823 ng*hr/mL	Standard Deviation 206
Part 1: Ruxolitinib + Siremadlin 20 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 5 n=2,4,1,0,0,0,0	872 ng*hr/mL	Standard Deviation 218
Part 1: Ruxolitinib + Siremadlin 20 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0	991 ng*hr/mL	Standard Deviation 183
Part 1: Ruxolitinib + Siremadlin 20 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 5 n=3,3,1,0,0,0,0,	465 ng*hr/mL	Standard Deviation 228
Part 1: Ruxolitinib + Siremadlin 20 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 2 Day 1 n=1,2,2,0,0,0,0	1040 ng*hr/mL	—
Part 1: Ruxolitinib + Siremadlin 20 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 5 n=1,1,2,0,0,0,0	849 ng*hr/mL	—
Part 1: Ruxolitinib + Siremadlin 30 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	673 ng*hr/mL	Standard Deviation 290
Part 1: Ruxolitinib + Siremadlin 30 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 5 n=3,3,1,0,0,0,0,	550 ng*hr/mL	Standard Deviation 307
Part 1: Ruxolitinib + Siremadlin 30 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 2 Day 1 n=3,3,1,0,0,0,0	727 ng*hr/mL	Standard Deviation 200
Part 1: Ruxolitinib + Siremadlin 30 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 2 Day 1 n=1,2,2,0,0,0,0	1190 ng*hr/mL	Standard Deviation 214
Part 1: Ruxolitinib + Siremadlin 30 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 2 Day 1 n=2,2,1,0,0,0,0	507 ng*hr/mL	Standard Deviation 225
Part 1: Ruxolitinib + Siremadlin 30 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 5 n=2,4,1,0,0,0,0	652 ng*hr/mL	Standard Deviation 218
Part 1: Ruxolitinib + Siremadlin 30 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0	616 ng*hr/mL	Standard Deviation 107
Part 1: Ruxolitinib + Siremadlin 30 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 5 n=1,1,2,0,0,0,0	901 ng*hr/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 2 Day 1 n=3,3,1,0,0,0,0	521 ng*hr/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	498 ng*hr/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2	481 ng*hr/mL	Standard Deviation 243
Part 1: Ruxolitinib + Siremadlin 40 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0	623 ng*hr/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 5 mg Cycle 1 Day 5 n=0,0,2,0,0,0,0	245 ng*hr/mL	Standard Deviation 173
Part 1: Ruxolitinib + Siremadlin 40 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 5 n=3,3,1,0,0,0,0,	441 ng*hr/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 5 n=1,1,2,0,0,0,0	454 ng*hr/mL	Standard Deviation 212
Part 1: Ruxolitinib + Siremadlin 40 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 5 n=2,4,1,0,0,0,0	482 ng*hr/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 5 mg Cycle 2 Day 1 n=0,0,1,0,0,0,0	172 ng*hr/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 2 Day 1 n=2,2,1,0,0,0,0	553 ng*hr/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 2 Day 1 n=1,2,2,0,0,0,0	334 ng*hr/mL	Standard Deviation 98.7
Part 1: Ruxolitinib + Siremadlin 40 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 5 mg Cycle 1 Day 1 n=0,0,2,1,0,0,0	344 ng*hr/mL	Standard Deviation 225
Part 1: Ruxolitinib + Rineterkib 200 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	633 ng*hr/mL	Standard Deviation 393
Part 1: Ruxolitinib + Rineterkib 200 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 25 mg Cycle 1 Day 1 n=0,0,0,1,0,0,1	188 ng*hr/mL	—
Part 1: Ruxolitinib + Rineterkib 200 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 5 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0	289 ng*hr/mL	—
Part 1: Ruxolitinib + Rineterkib 200 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 15 n=0,0,0,2,0,0,0	592 ng*hr/mL	Standard Deviation 403
Part 1: Ruxolitinib + Rineterkib 200 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0,	518 ng*hr/mL	—
Part 1: Ruxolitinib + Rineterkib 200 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 15 n=0,0,0,3,0,0,0	957 ng*hr/mL	Standard Deviation 479
Part 1: Ruxolitinib + Rineterkib 200 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 25 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0	718 ng*hr/mL	—
Part 1: Ruxolitinib + Rineterkib 200 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 5 mg Cycle 1 Day 1 n=0,0,2,1,0,0,0	199 ng*hr/mL	—
Part 1: Ruxolitinib + Rineterkib 200 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2	729 ng*hr/mL	—
Part 1: Ruxolitinib + Rineterkib 200 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0	913 ng*hr/mL	Standard Deviation 451
Part 1: Ruxolitinib + Crizanlizumab	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2	662 ng*hr/mL	Standard Deviation 420
Part 1: Ruxolitinib + Crizanlizumab	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	440 ng*hr/mL	—
Part 1: Ruxolitinib + Crizanlizumab	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0	887 ng*hr/mL	—
Part 1: Ruxolitinib + Sabatolimab	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	336 ng*hr/mL	Standard Deviation 30.6
Part 1: Ruxolitinib + NIS793	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2	1220 ng*hr/mL	Standard Deviation 637
Part 1: Ruxolitinib + NIS793	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	452 ng*hr/mL	—
Part 1: Ruxolitinib + NIS793	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1	Ruxolitinib 25 mg Cycle 1 Day 1 n=0,0,0,1,0,0,1	859 ng*hr/mL	—

Secondary

Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1

Time frame: Days 1 and 5 of Cycles 1 and 2 for siremadlin and Cycles 1 and 3 for crizanlizumab, sabatolimab, and NIS793; Days 1 and 15 of Cycle 1 for rineterkib

Population: The pharmacokinetic (PK) analysis set included all enrolled subjects who had an evaluable PK profile.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1: Ruxolitinib + Siremadlin 20 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	1520 ng*hr/mL	Standard Deviation 619
Part 1: Ruxolitinib + Siremadlin 20 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 5 n=6,7,5,0,0,0,0	2230 ng*hr/mL	Standard Deviation 1110
Part 1: Ruxolitinib + Siremadlin 20 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 1 n=5,6,3,0,0,0,0	1720 ng*hr/mL	Standard Deviation 1020
Part 1: Ruxolitinib + Siremadlin 20 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 5 n=3,5,3,0,0,0,0	1590 ng*hr/mL	Standard Deviation 577
Part 1: Ruxolitinib + Siremadlin 30 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 1 n=5,6,3,0,0,0,0	2400 ng*hr/mL	Standard Deviation 1150
Part 1: Ruxolitinib + Siremadlin 30 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	2560 ng*hr/mL	Standard Deviation 1530
Part 1: Ruxolitinib + Siremadlin 30 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 5 n=6,7,5,0,0,0,0	3340 ng*hr/mL	Standard Deviation 2120
Part 1: Ruxolitinib + Siremadlin 30 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 5 n=3,5,3,0,0,0,0	2860 ng*hr/mL	Standard Deviation 1680
Part 1: Ruxolitinib + Siremadlin 40 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 1 n=5,6,3,0,0,0,0	2870 ng*hr/mL	Standard Deviation 326
Part 1: Ruxolitinib + Siremadlin 40 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	3780 ng*hr/mL	Standard Deviation 1840
Part 1: Ruxolitinib + Siremadlin 40 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 5 n=6,7,5,0,0,0,0	4390 ng*hr/mL	Standard Deviation 2270
Part 1: Ruxolitinib + Siremadlin 40 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 5 n=3,5,3,0,0,0,0	3030 ng*hr/mL	Standard Deviation 786
Part 1: Ruxolitinib + Rineterkib 200 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	6000 ng*hr/mL	Standard Deviation 5120
Part 1: Ruxolitinib + Rineterkib 200 mg	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 15 n=0,0,0,9,0,0,0	15800 ng*hr/mL	Standard Deviation 11000
Part 1: Ruxolitinib + Crizanlizumab	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 3 Day 1 n=0,0,0,0,5,2,3	20900000 ng*hr/mL	Standard Deviation 13000000
Part 1: Ruxolitinib + Crizanlizumab	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	14100000 ng*hr/mL	Standard Deviation 4990000
Part 1: Ruxolitinib + Sabatolimab	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 3 Day 1 n=0,0,0,0,5,2,3	43500 ng*hr/mL	Standard Deviation 9110
Part 1: Ruxolitinib + Sabatolimab	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	34900 ng*hr/mL	Standard Deviation 7860
Part 1: Ruxolitinib + NIS793	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	103000000 ng*hr/mL	Standard Deviation 18700000
Part 1: Ruxolitinib + NIS793	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 3 Day 1 n=0,0,0,0,5,2,3	166000000 ng*hr/mL	Standard Deviation 63600000

Secondary

Change in Spleen Length From Baseline in Part 1

Change in spleen length measured in centimeters by manual palpation.

Time frame: Baseline, Week 24, Week 48

Population: The full analysis set included all subjects who received any study drug. Number analyzed is the number of participants with available data.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1: Ruxolitinib + Siremadlin 20 mg	Change in Spleen Length From Baseline in Part 1	Week 24 n=6,8,4,4,4,0,0	-3.3 centimeters	Standard Deviation 2.6
Part 1: Ruxolitinib + Siremadlin 20 mg	Change in Spleen Length From Baseline in Part 1	Week 48 n=2,1,2,1,1,0,0	-5.0 centimeters	Standard Deviation 0
Part 1: Ruxolitinib + Siremadlin 30 mg	Change in Spleen Length From Baseline in Part 1	Week 24 n=6,8,4,4,4,0,0	-5.5 centimeters	Standard Deviation 3.9
Part 1: Ruxolitinib + Siremadlin 30 mg	Change in Spleen Length From Baseline in Part 1	Week 48 n=2,1,2,1,1,0,0	-9.0 centimeters	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Change in Spleen Length From Baseline in Part 1	Week 24 n=6,8,4,4,4,0,0	-6.3 centimeters	Standard Deviation 4.6
Part 1: Ruxolitinib + Siremadlin 40 mg	Change in Spleen Length From Baseline in Part 1	Week 48 n=2,1,2,1,1,0,0	-6.0 centimeters	Standard Deviation 7.1
Part 1: Ruxolitinib + Rineterkib 200 mg	Change in Spleen Length From Baseline in Part 1	Week 48 n=2,1,2,1,1,0,0	-8.0 centimeters	—
Part 1: Ruxolitinib + Rineterkib 200 mg	Change in Spleen Length From Baseline in Part 1	Week 24 n=6,8,4,4,4,0,0	-1.8 centimeters	Standard Deviation 3.9
Part 1: Ruxolitinib + Crizanlizumab	Change in Spleen Length From Baseline in Part 1	Week 24 n=6,8,4,4,4,0,0	-1.5 centimeters	Standard Deviation 1.9
Part 1: Ruxolitinib + Crizanlizumab	Change in Spleen Length From Baseline in Part 1	Week 48 n=2,1,2,1,1,0,0	-5.0 centimeters	—

Secondary

Concentration Versus Time Profile for Crizanlizumab in Part 1

EOI = end of infusion

Time frame: Days 1, 2, 8, and 15 of Cycles 1, 2, and 3; Day 1 of Cycles 4, 5, 6, and 9. Each cycle was 28 days.

Population: The pharmacokinetic (PK) analysis set included all enrolled subjects who had an evaluable PK profile.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 1 Day 1, 0 H / PRE-INFUSION n=4	0 ng/mL	Standard Deviation 0
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 1 Day 1, 1H POST EOI n=5	114000 ng/mL	Standard Deviation 36400
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 1 Day 2, 24H POST START OF INFUSION n=4	78700 ng/mL	Standard Deviation 10500
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 1 Day 8, 168H POST START OF INFUSION n=5	28700 ng/mL	Standard Deviation 12200
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 1 Day 15, 336H POST START OF INFUSION n=5	9280 ng/mL	Standard Deviation 4540
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 1 Day 15, 0 H / PRE-INFUSION n=1	7710 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 2 Day 1, 0 H / PRE-INFUSION n=5	20700 ng/mL	Standard Deviation 8980
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 2 Day 1, 1H POST EOI n=5	135000 ng/mL	Standard Deviation 43100
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 2 Day 1, 336H POST START OF INFUSION n=1,	15500 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 3 Day 1, 672H POST START OF INFUSION n=5	8710 ng/mL	Standard Deviation 8350
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 3 Day 1, 0 H / PRE-INFUSION n=5	8710 ng/mL	Standard Deviation 8350
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 3 Day 1, 1H POST EOI n=4	103000 ng/mL	Standard Deviation 59200
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 3 Day 2, 24H POST START OF INFUSION n=5	95500 ng/mL	Standard Deviation 42300
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 3 Day 8, 168H POST START OF INFUSION n=5	37100 ng/mL	Standard Deviation 19400
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 3 Day 15, 336H POST START OF INFUSION n=5	21000 ng/mL	Standard Deviation 17700
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 4 Day 1, 672H POST START OF INFUSION n=5	5900 ng/mL	Standard Deviation 6710
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 4 Day 1, 0 H / PRE-INFUSION n=5	5900 ng/mL	Standard Deviation 6710
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 4 Day 1, 1H POST EOI n=5	128000 ng/mL	Standard Deviation 33200
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 5 Day 1, 672H POST START OF INFUSION n=4	6780 ng/mL	Standard Deviation 7830
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 5 Day 1, 0 H / PRE-INFUSION n=4	6780 ng/mL	Standard Deviation 7830
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 5 Day 1, 1H POST EOI n=3	122000 ng/mL	Standard Deviation 29400
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 6 Day 1, 672H POST START OF INFUSION n=4	6930 ng/mL	Standard Deviation 8000
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 6 Day 1, 0 H / PRE-INFUSION n=4	6930 ng/mL	Standard Deviation 8000
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 6 Day 1, 1H POST EOI n=4	128000 ng/mL	Standard Deviation 39600
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Crizanlizumab in Part 1	Cycle 9 Day 1, 0 H / PRE-INFUSION n=3	5500 ng/mL	Standard Deviation 9530

Secondary

Concentration Versus Time Profile for NIS793 in Part 1

EOI = end of infusion

Time frame: Days 1, 2, 4, 8, 11, and 15 of Cycles 1, 2, and 3; Day 1 of Cycles 4 and 5. Each cycle was 28 days.

Population: The pharmacokinetic (PK) analysis set included all enrolled subjects who had an evaluable PK profile.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 1 Day 1, 0 H / PRE-INFUSION n=4	0 ng/mL	Standard Deviation 0
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 1 Day 1, 1H POST EOI n=4	439000 ng/mL	Standard Deviation 56100
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 1 Day 2, 24H POST START OF INFUSION n=4	349000 ng/mL	Standard Deviation 52800
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 5 Day 1, 0 H / PRE-INFUSION n=1	280000 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 1 Day 4, 72H POST START OF INFUSION n=4	279000 ng/mL	Standard Deviation 48400
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 1 Day 8, 168H POST START OF INFUSION n=3	196000 ng/mL	Standard Deviation 31000
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 1 Day 11, 240H POST START OF INFUSION n=4	183000 ng/mL	Standard Deviation 45400
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 1 Day 15, 336H POST START OF INFUSION n=4	161000 ng/mL	Standard Deviation 37500
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 2 Day 1, 504H POST START OF INFUSION n=4	132000 ng/mL	Standard Deviation 33300
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 2 Day 1, 0 H / PRE-INFUSION n=4	132000 ng/mL	Standard Deviation 33300
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 3 Day 1, 0 H / PRE-INFUSION n=3	187000 ng/mL	Standard Deviation 61000
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 3 Day 1, 1H POST EOI n=3	743000 ng/mL	Standard Deviation 314000
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 3 Day 2, 24H POST START OF INFUSION n=2	632000 ng/mL	Standard Deviation 17000
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 3 Day 4, 72H POST START OF INFUSION n=3	448000 ng/mL	Standard Deviation 114000
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 3 Day 8, 168H POST START OF INFUSION n=3	383000 ng/mL	Standard Deviation 103000
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 3 Day 11, 240H POST START OF INFUSION n=2	262000 ng/mL	Standard Deviation 93300
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 3 Day 15, 336H POST START OF INFUSION n=3	265000 ng/mL	Standard Deviation 51500
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 4 Day 1, 504H POST START OF INFUSION n=1	281000 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for NIS793 in Part 1	Cycle 4 Day 1, 0 H / PRE-INFUSION n=2	232000 ng/mL	Standard Deviation 70000

Secondary

Concentration Versus Time Profile for Rineterkib in Part 1

Time frame: Days 1, 2, 15, and 16 of Cycle 1; Day 1 of Cycles 2, 3, 4, 5, and 6. Each cycle was 28 days.

Population: The pharmacokinetic (PK) analysis set included all enrolled subjects who had an evaluable PK profile.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 1, 0 hr (pre-dose) n=9	0 ng/mL	Standard Deviation 0
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 1, 0.5 hr n=9	68.3 ng/mL	Standard Deviation 68.8
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 1, 1 hr n=8	235 ng/mL	Standard Deviation 343
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 1, 2 hr n=8	340 ng/mL	Standard Deviation 229
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 1, 3 hr n=9	352 ng/mL	Standard Deviation 244
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 1, 4 hr n=9	325 ng/mL	Standard Deviation 173
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 1, 8 hr n=7	244 ng/mL	Standard Deviation 128
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 2, 24 hr n=9	261 ng/mL	Standard Deviation 419
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 2, 0 hr (pre-dose) n=8	234 ng/mL	Standard Deviation 440
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 15, 0 hr (pre-dose) n=8	330 ng/mL	Standard Deviation 222
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 15 0.5 hr n=8	581 ng/mL	Standard Deviation 464
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 15, 1 hr n=n=9	735 ng/mL	Standard Deviation 620
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 15, 2 hr n=8	749 ng/mL	Standard Deviation 512
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 15, 3 hr n=8	789 ng/mL	Standard Deviation 616
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 15, 4 hr n=8	771 ng/mL	Standard Deviation 484
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 15, 8 hr n=9	633 ng/mL	Standard Deviation 403
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 16, 24 hr n=8	528 ng/mL	Standard Deviation 618
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 1 Day 16, 0 hr (pre-dose) n=8	305 ng/mL	Standard Deviation 222
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 2 Day 1, 0 hr (pre-dose) n=9	314 ng/mL	Standard Deviation 171
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 3 Day 1, 0 hr (pre-dose) n=6	406 ng/mL	Standard Deviation 341
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 4 Day 1, 0 hr (pre-dose) n=5	402 ng/mL	Standard Deviation 364
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 5 Day 1, 0 hr (pre-dose) n=3	232 ng/mL	Standard Deviation 165
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Rineterkib in Part 1	Cycle 6 Day 1, 0 hr (pre-dose) n=3	340 ng/mL	Standard Deviation 125

Secondary

Concentration Versus Time Profile for Ruxolitinib in Part 1

Time frame: Days 1, 2, 5, 6, and 15 of Cycles 1 and 2; Day 16 of Cycle 1; Days 1, 2, and 15 of Cycle 3; Days 1 and 5 of Cycles 4, 5, and 6. Each cycle was 28 days.

Population: The pharmacokinetic (PK) analysis set included all enrolled subjects who had an evaluable PK profile.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 2, 0 hr (pre-dose) n=7,6,4,8,1,1,0	18.2 ng/mL	Standard Deviation 13
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 4 hr n=5,7,5,0,0,0,0	89.9 ng/mL	Standard Deviation 39.8
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 4 hr n=6,8,6,0,0,0,0	81.4 ng/mL	Standard Deviation 38.4
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 3 hr n=6,8,6,0,0,0,0	104 ng/mL	Standard Deviation 45.2
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 0 hr (pre-dose) n=6,8,6,0,0,0,0	15.5 ng/mL	Standard Deviation 13.9
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 1 hr n=6,7,6,0,0,0,0	160 ng/mL	Standard Deviation 79.5
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 2 hr n=6,8,6,0,0,0,0	149 ng/mL	Standard Deviation 64
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 3 Day 2, 0 hr (pre-dose) n=5,6,3,0,0,0,0	12.6 ng/mL	Standard Deviation 13.9
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 0 hr (pre-dose) n=6,6,5,7,3,2,4	34.7 ng/mL	Standard Deviation 17.8
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 3 Day 15, 0 hr (pre-dose) n=5,5,2,0,4,2,0	18.7 ng/mL	Standard Deviation 18.4
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 5 Day 5, 0 hr (pre-dose) n=5,3,3,0,0,0,0	26.6 ng/mL	Standard Deviation 16.4
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 4 Day 1, 0 hr (pre-dose) n=7,5,3,5,4,1,1	17.5 ng/mL	Standard Deviation 18.2
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 0.5 hr n=6,5,6,8,2,2,3	284 ng/mL	Standard Deviation 128
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 5 Day 1, 0 hr (pre-dose) n=7,6,4,3,3,0,0	16.4 ng/mL	Standard Deviation 16.1
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 4 Day 5, 0 hr (pre-dose) n=5,6,3,0,0,0,0	13.6 ng/mL	Standard Deviation 13.7
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 6 Day 5, 0 hr (pre-dose) n=3,4,2,0,0,0,0	24.8 ng/mL	Standard Deviation 19.9
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 3 Day 1, 0 hr (pre-dose) n=7,7,4,6,4,2,2	24.2 ng/mL	Standard Deviation 15.5
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 15, 0 hr (pre-dose) n=6,8,3,0,1,2,0	22.4 ng/mL	Standard Deviation 17.2
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 1 hr n=6,6,6,7,2,2,3	240 ng/mL	Standard Deviation 78.9
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 6, 0 hr (pre-dose) n=4,5,4,0,0,0,0	7.36 ng/mL	Standard Deviation 7.32
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 5, 0 hr (pre-dose) n=3,8,4,0,0,0,0	15.4 ng/mL	Standard Deviation 6.29
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 2 hr n=6,6,6,7,2,2,3	174 ng/mL	Standard Deviation 55.3
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 6 Day 1, 0 hr (pre-dose) n=4,4,2,3,3,0,0	15.8 ng/mL	Standard Deviation 19.5
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 2, 0 hr (pre-dose) n=3,6,5,0,0,0,0	74.0 ng/mL	Standard Deviation 62.3
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 8 hr n=4,6,5,0,0,0,0	47.3 ng/mL	Standard Deviation 31.5
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 3 hr n=6,6,5,8,2,2,3	125 ng/mL	Standard Deviation 36.6
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 3 hr n=6,7,5,0,0,0,0	108 ng/mL	Standard Deviation 50.8
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 2 hr n=6,7,4,0,0,0,0	144 ng/mL	Standard Deviation 76
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 1 hr n=6,7,5,0,0,0,0	212 ng/mL	Standard Deviation 89.8
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 4 hr n=6,6,6,8,2,2,3	93.2 ng/mL	Standard Deviation 26.5
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 0 hr (pre-dose) n=6,7,5,8,4,2,3	25.9 ng/mL	Standard Deviation 23.4
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 15, 0 hr (pre-dose) n=7,8,4,7,3,2,0	23.2 ng/mL	Standard Deviation 34
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 8 hr n=6,6,6,8,4,2,3	51.6 ng/mL	Standard Deviation 18.7
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 6, 0 hr (pre-dose) n=6,7,5,0,0,0,0	11.5 ng/mL	Standard Deviation 12.1
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 8 hr n=6,8,4,0,0,0,0	37.6 ng/mL	Standard Deviation 22.6
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 1 hr n=6,7,5,0,0,0,0	186 ng/mL	Standard Deviation 113
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 2, 0 hr (pre-dose) n=7,6,4,8,1,1,0	13.4 ng/mL	Standard Deviation 11.1
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 1 hr n=6,6,6,7,2,2,3	167 ng/mL	Standard Deviation 51.7
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 6 Day 1, 0 hr (pre-dose) n=4,4,2,3,3,0,0	17.0 ng/mL	Standard Deviation 19.7
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 3 hr n=6,8,6,0,0,0,0	100 ng/mL	Standard Deviation 39.1
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 8 hr n=6,8,4,0,0,0,0	22.9 ng/mL	Standard Deviation 13.7
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 5, 0 hr (pre-dose) n=3,8,4,0,0,0,0	15.2 ng/mL	Standard Deviation 11.3
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 0 hr (pre-dose) n=6,8,6,0,0,0,0	14.7 ng/mL	Standard Deviation 14
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 4 hr n=5,7,5,0,0,0,0	106 ng/mL	Standard Deviation 39.5
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 0 hr (pre-dose) n=6,7,5,8,4,2,3	19.3 ng/mL	Standard Deviation 18.8
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 1 hr n=6,7,6,0,0,0,0	221 ng/mL	Standard Deviation 83.7
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 5 Day 5, 0 hr (pre-dose) n=5,3,3,0,0,0,0	9.54 ng/mL	Standard Deviation 13.2
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 2, 0 hr (pre-dose) n=3,6,5,0,0,0,0	19.2 ng/mL	Standard Deviation 19.7
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 2 hr n=6,8,6,0,0,0,0	140 ng/mL	Standard Deviation 45.6
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 8 hr n=6,6,6,8,4,2,3	32.2 ng/mL	Standard Deviation 19.1
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 3 Day 2, 0 hr (pre-dose) n=5,6,3,0,0,0,0	31.9 ng/mL	Standard Deviation 38.9
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 2 hr n=6,6,6,7,2,2,3	143 ng/mL	Standard Deviation 48.6
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 4 hr n=6,6,6,8,2,2,3	77.8 ng/mL	Standard Deviation 40
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 3 Day 15, 0 hr (pre-dose) n=5,5,2,0,4,2,0	45.2 ng/mL	Standard Deviation 41.5
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 6 Day 5, 0 hr (pre-dose) n=3,4,2,0,0,0,0	11.5 ng/mL	Standard Deviation 8.34
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 3 hr n=6,7,5,0,0,0,0	127 ng/mL	Standard Deviation 61.7
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 5 Day 1, 0 hr (pre-dose) n=7,6,4,3,3,0,0	12.7 ng/mL	Standard Deviation 12
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 8 hr n=4,6,5,0,0,0,0	45.8 ng/mL	Standard Deviation 19.4
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 4 Day 1, 0 hr (pre-dose) n=7,5,3,5,4,1,1	20.9 ng/mL	Standard Deviation 22.2
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 0 hr (pre-dose) n=6,6,5,7,3,2,4	21.3 ng/mL	Standard Deviation 14.5
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 2 hr n=6,7,4,0,0,0,0	165 ng/mL	Standard Deviation 82.2
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 4 Day 5, 0 hr (pre-dose) n=5,6,3,0,0,0,0	9.12 ng/mL	Standard Deviation 13.5
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 15, 0 hr (pre-dose) n=7,8,4,7,3,2,0	23.6 ng/mL	Standard Deviation 19.8
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 3 Day 1, 0 hr (pre-dose) n=7,7,4,6,4,2,2	23.2 ng/mL	Standard Deviation 21.8
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 0.5 hr n=6,5,6,8,2,2,3	152 ng/mL	Standard Deviation 91.1
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 3 hr n=6,6,5,8,2,2,3	114 ng/mL	Standard Deviation 42.1
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 4 hr n=6,8,6,0,0,0,0	71.2 ng/mL	Standard Deviation 30.1
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 15, 0 hr (pre-dose) n=6,8,3,0,1,2,0	22.1 ng/mL	Standard Deviation 22.7
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 6, 0 hr (pre-dose) n=6,7,5,0,0,0,0	37.8 ng/mL	Standard Deviation 63.4
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 6, 0 hr (pre-dose) n=4,5,4,0,0,0,0	46.8 ng/mL	Standard Deviation 80
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 6 Day 5, 0 hr (pre-dose) n=3,4,2,0,0,0,0	0.957 ng/mL	Standard Deviation 0.528
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 0 hr (pre-dose) n=6,6,5,7,3,2,4	11.8 ng/mL	Standard Deviation 13.4
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 3 hr n=6,7,5,0,0,0,0	50.3 ng/mL	Standard Deviation 26.4
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 3 Day 2, 0 hr (pre-dose) n=5,6,3,0,0,0,0	2.33 ng/mL	Standard Deviation 1.57
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 3 Day 15, 0 hr (pre-dose) n=5,5,2,0,4,2,0	3.95 ng/mL	Standard Deviation 4.1
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 0.5 hr n=6,5,6,8,2,2,3	95.7 ng/mL	Standard Deviation 63.2
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 1 hr n=6,6,6,7,2,2,3	124 ng/mL	Standard Deviation 64.5
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 2 hr n=6,6,6,7,2,2,3	98.9 ng/mL	Standard Deviation 46.2
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 3 hr n=6,6,5,8,2,2,3	62.4 ng/mL	Standard Deviation 31.1
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 4 hr n=6,6,6,8,2,2,3	50.2 ng/mL	Standard Deviation 23.4
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 8 hr n=6,6,6,8,4,2,3	24.0 ng/mL	Standard Deviation 15
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 2, 0 hr (pre-dose) n=7,6,4,8,1,1,0	11.2 ng/mL	Standard Deviation 16.2
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 0 hr (pre-dose) n=6,8,6,0,0,0,0	9.33 ng/mL	Standard Deviation 10.6
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 1 hr n=6,7,6,0,0,0,0	130 ng/mL	Standard Deviation 66.6
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 2 hr n=6,8,6,0,0,0,0	90.0 ng/mL	Standard Deviation 41.4
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 3 hr n=6,8,6,0,0,0,0	61.8 ng/mL	Standard Deviation 31.7
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 4 hr n=6,8,6,0,0,0,0	34.1 ng/mL	Standard Deviation 16.1
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 5, 8 hr n=6,8,4,0,0,0,0	16.2 ng/mL	Standard Deviation 13.4
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 6, 0 hr (pre-dose) n=6,7,5,0,0,0,0	6.28 ng/mL	Standard Deviation 9.31
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 15, 0 hr (pre-dose) n=7,8,4,7,3,2,0	11.2 ng/mL	Standard Deviation 17.4
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 0 hr (pre-dose) n=6,7,5,8,4,2,3	11.4 ng/mL	Standard Deviation 20.7
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 1 hr n=6,7,5,0,0,0,0	114 ng/mL	Standard Deviation 82.4
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 2 hr n=6,7,4,0,0,0,0	56.2 ng/mL	Standard Deviation 30.9
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 4 hr n=5,7,5,0,0,0,0	45.6 ng/mL	Standard Deviation 25.8
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 8 hr n=4,6,5,0,0,0,0	30.9 ng/mL	Standard Deviation 28.1
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 2, 0 hr (pre-dose) n=3,6,5,0,0,0,0	13.9 ng/mL	Standard Deviation 20.5
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 5, 0 hr (pre-dose) n=3,8,4,0,0,0,0	4.45 ng/mL	Standard Deviation 4.57
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 6, 0 hr (pre-dose) n=4,5,4,0,0,0,0	2.40 ng/mL	Standard Deviation 2.74
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 15, 0 hr (pre-dose) n=6,8,3,0,1,2,0	1.93 ng/mL	Standard Deviation 1.65
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 3 Day 1, 0 hr (pre-dose) n=7,7,4,6,4,2,2	4.50 ng/mL	Standard Deviation 4.03
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 4 Day 1, 0 hr (pre-dose) n=7,5,3,5,4,1,1	4.53 ng/mL	Standard Deviation 6.44
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 4 Day 5, 0 hr (pre-dose) n=5,6,3,0,0,0,0	7.99 ng/mL	Standard Deviation 11.4
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 5 Day 1, 0 hr (pre-dose) n=7,6,4,3,3,0,0	5.30 ng/mL	Standard Deviation 5.94
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 5 Day 5, 0 hr (pre-dose) n=5,3,3,0,0,0,0	2.79 ng/mL	Standard Deviation 2.46
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 6 Day 1, 0 hr (pre-dose) n=4,4,2,3,3,0,0	0.608 ng/mL	Standard Deviation 0.0672
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 6 Day 1, 0 hr (pre-dose) n=4,4,2,3,3,0,0	21.9 ng/mL	Standard Deviation 23.2
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 4 Day 1, 0 hr (pre-dose) n=7,5,3,5,4,1,1	18.2 ng/mL	Standard Deviation 33.8
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 8 hr n=6,6,6,8,4,2,3	29.9 ng/mL	Standard Deviation 19.8
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 5 Day 1, 0 hr (pre-dose) n=7,6,4,3,3,0,0	10.3 ng/mL	Standard Deviation 13.6
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 2 hr n=6,6,6,7,2,2,3	140 ng/mL	Standard Deviation 112
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 15, 0 hr (pre-dose) n=7,8,4,7,3,2,0	11.9 ng/mL	Standard Deviation 14.2
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 0 hr (pre-dose) n=6,6,5,7,3,2,4	20.1 ng/mL	Standard Deviation 16.1
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 15, 1 hr n=0,0,0,8,0,0,0	194 ng/mL	Standard Deviation 139
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 15, 3 hr n=0,0,0,7,0,0,0	103 ng/mL	Standard Deviation 59.6
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 1 hr n=6,6,6,7,2,2,3	192 ng/mL	Standard Deviation 106
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 16, 0 hr (pre-dose) n=0,0,0,6,0,0,0	14.4 ng/mL	Standard Deviation 15.2
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 15, 0.5 hr n=0,0,0,7,0,0,0	231 ng/mL	Standard Deviation 115
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 15, 8 hr n=0,0,0,8,0,0,0	27.9 ng/mL	Standard Deviation 21.7
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 0 hr (pre-dose) n=6,7,5,8,4,2,3	45.7 ng/mL	Standard Deviation 108
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 0.5 hr n=6,5,6,8,2,2,3	185 ng/mL	Standard Deviation 100
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 4 hr n=6,6,6,8,2,2,3	59.2 ng/mL	Standard Deviation 46.1
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 15, 2 hr n=0,0,0,7,0,0,0	126 ng/mL	Standard Deviation 58.7
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 3 Day 1, 0 hr (pre-dose) n=7,7,4,6,4,2,2	11.1 ng/mL	Standard Deviation 10.9
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 15, 4 hr n=0,0,0,7,0,0,0	76.3 ng/mL	Standard Deviation 53.5
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 3 hr n=6,6,5,8,2,2,3	97.4 ng/mL	Standard Deviation 75.7
Part 1: Ruxolitinib + Rineterkib 200 mg	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 2, 0 hr (pre-dose) n=7,6,4,8,1,1,0	17.6 ng/mL	Standard Deviation 19.9
Part 1: Ruxolitinib + Crizanlizumab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 4 Day 1, 0 hr (pre-dose) n=7,5,3,5,4,1,1	14.0 ng/mL	Standard Deviation 7.81
Part 1: Ruxolitinib + Crizanlizumab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 4 hr n=6,6,6,8,2,2,3	101 ng/mL	Standard Deviation 81.2
Part 1: Ruxolitinib + Crizanlizumab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 15, 0 hr (pre-dose) n=6,8,3,0,1,2,0	63.6 ng/mL	—
Part 1: Ruxolitinib + Crizanlizumab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 2, 0 hr (pre-dose) n=7,6,4,8,1,1,0	30.3 ng/mL	—
Part 1: Ruxolitinib + Crizanlizumab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 6 Day 1, 0 hr (pre-dose) n=4,4,2,3,3,0,0	27.3 ng/mL	Standard Deviation 32.8
Part 1: Ruxolitinib + Crizanlizumab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 3 hr n=6,6,5,8,2,2,3	124 ng/mL	Standard Deviation 91
Part 1: Ruxolitinib + Crizanlizumab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 1 hr n=6,6,6,7,2,2,3	65.7 ng/mL	Standard Deviation 59.9
Part 1: Ruxolitinib + Crizanlizumab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 15, 0 hr (pre-dose) n=7,8,4,7,3,2,0	12.6 ng/mL	Standard Deviation 10.1
Part 1: Ruxolitinib + Crizanlizumab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 0.5 hr n=6,5,6,8,2,2,3	107 ng/mL	Standard Deviation 119
Part 1: Ruxolitinib + Crizanlizumab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 8 hr n=6,6,6,8,4,2,3	39.5 ng/mL	Standard Deviation 29.2
Part 1: Ruxolitinib + Crizanlizumab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 0 hr (pre-dose) n=6,6,5,7,3,2,4	12.9 ng/mL	Standard Deviation 6.31
Part 1: Ruxolitinib + Crizanlizumab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 5 Day 1, 0 hr (pre-dose) n=7,6,4,3,3,0,0	20.1 ng/mL	Standard Deviation 23
Part 1: Ruxolitinib + Crizanlizumab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 0 hr (pre-dose) n=6,7,5,8,4,2,3	13.7 ng/mL	Standard Deviation 4.84
Part 1: Ruxolitinib + Crizanlizumab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 2 hr n=6,6,6,7,2,2,3	170 ng/mL	Standard Deviation 140
Part 1: Ruxolitinib + Crizanlizumab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 3 Day 15, 0 hr (pre-dose) n=5,5,2,0,4,2,0	10.9 ng/mL	Standard Deviation 6.89
Part 1: Ruxolitinib + Crizanlizumab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 3 Day 1, 0 hr (pre-dose) n=7,7,4,6,4,2,2	12.0 ng/mL	Standard Deviation 6.36
Part 1: Ruxolitinib + Sabatolimab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 4 hr n=6,6,6,8,2,2,3	28.3 ng/mL	Standard Deviation 7.28
Part 1: Ruxolitinib + Sabatolimab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 3 Day 15, 0 hr (pre-dose) n=5,5,2,0,4,2,0	12.5 ng/mL	Standard Deviation 9.14
Part 1: Ruxolitinib + Sabatolimab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 0 hr (pre-dose) n=6,7,5,8,4,2,3	28.4 ng/mL	Standard Deviation 39.1
Part 1: Ruxolitinib + Sabatolimab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 3 hr n=6,6,5,8,2,2,3	54.4 ng/mL	Standard Deviation 10.4
Part 1: Ruxolitinib + Sabatolimab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 2 hr n=6,6,6,7,2,2,3	72.7 ng/mL	Standard Deviation 4.1
Part 1: Ruxolitinib + Sabatolimab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 1 hr n=6,6,6,7,2,2,3	110 ng/mL	Standard Deviation 44.1
Part 1: Ruxolitinib + Sabatolimab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 0.5 hr n=6,5,6,8,2,2,3	57.1 ng/mL	Standard Deviation 44
Part 1: Ruxolitinib + Sabatolimab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 15, 0 hr (pre-dose) n=6,8,3,0,1,2,0	7.95 ng/mL	Standard Deviation 8.14
Part 1: Ruxolitinib + Sabatolimab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 3 Day 1, 0 hr (pre-dose) n=7,7,4,6,4,2,2	2.44 ng/mL	Standard Deviation 1.46
Part 1: Ruxolitinib + Sabatolimab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 4 Day 1, 0 hr (pre-dose) n=7,5,3,5,4,1,1	2.94 ng/mL	—
Part 1: Ruxolitinib + Sabatolimab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 2, 0 hr (pre-dose) n=7,6,4,8,1,1,0	0 ng/mL	—
Part 1: Ruxolitinib + Sabatolimab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 0 hr (pre-dose) n=6,6,5,7,3,2,4	51.2 ng/mL	Standard Deviation 61
Part 1: Ruxolitinib + Sabatolimab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 8 hr n=6,6,6,8,4,2,3	7.75 ng/mL	Standard Deviation 1.52
Part 1: Ruxolitinib + Sabatolimab	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 15, 0 hr (pre-dose) n=7,8,4,7,3,2,0	4.06 ng/mL	Standard Deviation 2.28
Part 1: Ruxolitinib + NIS793	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 4 hr n=6,6,6,8,2,2,3	190 ng/mL	Standard Deviation 58.4
Part 1: Ruxolitinib + NIS793	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 4 Day 1, 0 hr (pre-dose) n=7,5,3,5,4,1,1	24.4 ng/mL	—
Part 1: Ruxolitinib + NIS793	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 0 hr (pre-dose) n=6,6,5,7,3,2,4	37.9 ng/mL	Standard Deviation 48.4
Part 1: Ruxolitinib + NIS793	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 0.5 hr n=6,5,6,8,2,2,3	108 ng/mL	Standard Deviation 128
Part 1: Ruxolitinib + NIS793	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 3 Day 1, 0 hr (pre-dose) n=7,7,4,6,4,2,2	84.6 ng/mL	Standard Deviation 96.8
Part 1: Ruxolitinib + NIS793	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 1 hr n=6,6,6,7,2,2,3	164 ng/mL	Standard Deviation 140
Part 1: Ruxolitinib + NIS793	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 2 hr n=6,6,6,7,2,2,3	187 ng/mL	Standard Deviation 105
Part 1: Ruxolitinib + NIS793	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 3 hr n=6,6,5,8,2,2,3	184 ng/mL	Standard Deviation 77.9
Part 1: Ruxolitinib + NIS793	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 2 Day 1, 0 hr (pre-dose) n=6,7,5,8,4,2,3	65.1 ng/mL	Standard Deviation 88.9
Part 1: Ruxolitinib + NIS793	Concentration Versus Time Profile for Ruxolitinib in Part 1	Cycle 1 Day 1, 8 hr n=6,6,6,8,4,2,3	44.4 ng/mL	Standard Deviation 35.3

Secondary

Concentration Versus Time Profile for Sabatolimab in Part 1

EOI = end of infusion

Time frame: Days 1, 2, 8, and 15 of Cycles 1, 2, and 3; Day 1 of Cycles 4 and 5. Each cycle was 28 days.

Population: The pharmacokinetic (PK) analysis set included all enrolled subjects who had an evaluable PK profile.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 3 Day 15, 336H POST START OF INFUSION n=2	58.0 ng/mL	Standard Deviation 12.3
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 4 Day 1, 672H POST START OF INFUSION n=1	31.1 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 4 Day 1, 0 H / PRE-INFUSION n=2	30.0 ng/mL	Standard Deviation 1.56
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 4 Day 1, 1H POST EOI n=2	141 ng/mL	Standard Deviation 11.3
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 5 Day 1, 0 H / PRE-INFUSION n=2	32.9 ng/mL	Standard Deviation 3.82
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 5 Day 1, 1H POST EOI n=2	152 ng/mL	Standard Deviation 9.19
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 1 Day 1, 0 H / PRE-INFUSION n=2	0 ng/mL	Standard Deviation 0
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 1 Day 1, 1H POST EOI n=1	143 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 1 Day 2, 24H POST START OF INFUSION n=2	109 ng/mL	Standard Deviation 13.2
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 1 Day 8, 168H POST START OF INFUSION n=1	57.0 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 1 Day 15, 336H POST START OF INFUSION n=2	41.8 ng/mL	Standard Deviation 7.28
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 2 Day 1, 672H POST START OF INFUSION n=2	16.1 ng/mL	Standard Deviation 9.16
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 2 Day 1, 0 H / PRE-INFUSION n=2	16.1 ng/mL	Standard Deviation 9.16
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 2 Day 1, 1H POST EOI n=1	126 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 3 Day 1, 672H POST START OF INFUSION n=2	26.0 ng/mL	Standard Deviation 5.09
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 3 Day 1, 0 H / PRE-INFUSION n=2	26.0 ng/mL	Standard Deviation 5.09
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 3 Day 1, 1H POST EOI n=2	150 ng/mL	Standard Deviation 33.2
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 3 Day 2, 24H POST START OF INFUSION n=2	125 ng/mL	Standard Deviation 10.6
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Sabatolimab in Part 1	Cycle 3 Day 8, 168H POST START OF INFUSION n=2	80.5 ng/mL	Standard Deviation 19.1

Secondary

Concentration Versus Time Profile for Siremadlin in Part 1

Time frame: Day 1 of Cycles 1 and 2; Day 6 of Cycle 1; Days 2 and 5 of Cycles 1, 2, 3, 4, 5, and 6. Each cycle was 28 days.

Population: The pharmacokinetic (PK) analysis set included all enrolled subjects who had an evaluable PK profile.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 4 hr n=6,9,5	92.9 ng/mL	Standard Deviation 44
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 6, 24 hr n=4,5,3	34.7 ng/mL	Standard Deviation 13.2
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 3 Day 5, 0 hr (pre-dose) n=5,6,3	56.8 ng/mL	Standard Deviation 47.9
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 3 hr n=6,9,4	102 ng/mL	Standard Deviation 51.8
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 3 Day 2, 0 hr (pre-dose) n=3,4,4	43.5 ng/mL	Standard Deviation 16.5
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5, 4 hr n=5,7,5	133 ng/mL	Standard Deviation 67.4
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 2 hr n=6,9,5	104 ng/mL	Standard Deviation 53.3
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 1 hr n=6,9,5	52.7 ng/mL	Standard Deviation 27
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 4 Day 5, 0 hr (pre-dose) n=5,6,1	40.4 ng/mL	Standard Deviation 29.7
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 1 hr n=5,5,3	71.8 ng/mL	Standard Deviation 92.9
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 0.5 hr n=6,8,5	7.46 ng/mL	Standard Deviation 6.23
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 5 Day 2, 0 hr (pre-dose) n=6,4,4	40.0 ng/mL	Standard Deviation 29.3
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 8 hr n=4,5,3	90.9 ng/mL	Standard Deviation 39.1
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 6 Day 5, 0 hr (pre-dose) n=4,2,1	79.0 ng/mL	Standard Deviation 52.2
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 5 Day 5, 0 hr (pre-dose) n=6,4,3	78.3 ng/mL	Standard Deviation 90.2
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5, 3 hr n=6,7,5	144 ng/mL	Standard Deviation 74.6
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 6 Day 2, 0 hr (pre-dose) n=5,2,1	48.0 ng/mL	Standard Deviation 28.2
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 2 hr n=5,5,2	116 ng/mL	Standard Deviation 64.7
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 4 Day 2, 0 hr (pre-dose) n=5,5,1	36.3 ng/mL	Standard Deviation 21.7
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5, 2 hr n=6,7,5	127 ng/mL	Standard Deviation 63.7
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 3 hr n=5,5,3	111 ng/mL	Standard Deviation 58.2
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 0 hr (pre-dose) n=6,7,5	0 ng/mL	Standard Deviation 0
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5,1 hr n=6,6,5	72.9 ng/mL	Standard Deviation 28.3
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 4 hr n=5,5,3	114 ng/mL	Standard Deviation 52.8
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5, 0 hr (pre-dose) n=6,7,5	43.5 ng/mL	Standard Deviation 42.2
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 2, 24 hr n=4,5,3	67.3 ng/mL	Standard Deviation 49.3
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 6, 24 hr n=7,8,5	45.4 ng/mL	Standard Deviation 35.9
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 2, 24 hr n=6,10,4	42.0 ng/mL	Standard Deviation 23.7
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 5, 0 hr (pre-dose) n=4,7,3	24.3 ng/mL	Standard Deviation 23.8
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5, 8 hr n=7,8,3	110 ng/mL	Standard Deviation 54.3
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 8 hr n=6,9,5	75.7 ng/mL	Standard Deviation 36.9
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 5, 3 hr n=3,6,3	103 ng/mL	Standard Deviation 34.1
Part 1: Ruxolitinib + Siremadlin 20 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 0 hr (pre-dose) n=4,5,3	0 ng/mL	Standard Deviation 0
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 4 hr n=5,5,3	158 ng/mL	Standard Deviation 78.4
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 8 hr n=4,5,3	122 ng/mL	Standard Deviation 54.5
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 3 Day 5, 0 hr (pre-dose) n=5,6,3	81.0 ng/mL	Standard Deviation 73.9
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 4 Day 2, 0 hr (pre-dose) n=5,5,1	63.0 ng/mL	Standard Deviation 52.4
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 2 hr n=6,9,5	146 ng/mL	Standard Deviation 95.1
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 0 hr (pre-dose) n=4,5,3	0 ng/mL	Standard Deviation 0
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 1 hr n=5,5,3	25.5 ng/mL	Standard Deviation 28.4
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 2 hr n=5,5,2	100 ng/mL	Standard Deviation 64.8
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 3 hr n=5,5,3	146 ng/mL	Standard Deviation 99.5
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 2, 24 hr n=4,5,3	48.5 ng/mL	Standard Deviation 44.2
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 5, 0 hr (pre-dose) n=4,7,3	42.5 ng/mL	Standard Deviation 50.8
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 5, 3 hr n=3,6,3	181 ng/mL	Standard Deviation 89.7
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 6, 24 hr n=4,5,3	51.5 ng/mL	Standard Deviation 58.3
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 3 Day 2, 0 hr (pre-dose) n=3,4,4	79.1 ng/mL	Standard Deviation 96.9
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 4 Day 5, 0 hr (pre-dose) n=5,6,1	50.1 ng/mL	Standard Deviation 48.1
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 5 Day 2, 0 hr (pre-dose) n=6,4,4	146 ng/mL	Standard Deviation 180
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 5 Day 5, 0 hr (pre-dose) n=6,4,3	124 ng/mL	Standard Deviation 129
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 6 Day 2, 0 hr (pre-dose) n=5,2,1	60.2 ng/mL	Standard Deviation 37
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 6 Day 5, 0 hr (pre-dose) n=4,2,1	68.9 ng/mL	Standard Deviation 68.1
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 0 hr (pre-dose) n=6,7,5	0 ng/mL	Standard Deviation 0
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 0.5 hr n=6,8,5	4.76 ng/mL	Standard Deviation 8.02
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 1 hr n=6,9,5	38.8 ng/mL	Standard Deviation 40.9
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 3 hr n=6,9,4	178 ng/mL	Standard Deviation 96.3
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 4 hr n=6,9,5	181 ng/mL	Standard Deviation 116
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 8 hr n=6,9,5	146 ng/mL	Standard Deviation 77
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 2, 24 hr n=6,10,4	59.7 ng/mL	Standard Deviation 49.4
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5, 0 hr (pre-dose) n=6,7,5	88.4 ng/mL	Standard Deviation 73.6
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5,1 hr n=6,6,5	171 ng/mL	Standard Deviation 89.8
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5, 2 hr n=6,7,5	260 ng/mL	Standard Deviation 128
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5, 3 hr n=6,7,5	260 ng/mL	Standard Deviation 130
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5, 4 hr n=5,7,5	226 ng/mL	Standard Deviation 111
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5, 8 hr n=7,8,3	160 ng/mL	Standard Deviation 83.1
Part 1: Ruxolitinib + Siremadlin 30 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 6, 24 hr n=7,8,5	75.1 ng/mL	Standard Deviation 66.5
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 6, 24 hr n=4,5,3	27.5 ng/mL	Standard Deviation 6.45
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5, 8 hr n=7,8,3	247 ng/mL	Standard Deviation 126
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 3 hr n=6,9,4	192 ng/mL	Standard Deviation 137
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 5, 3 hr n=3,6,3	228 ng/mL	Standard Deviation 58.3
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5, 3 hr n=6,7,5	333 ng/mL	Standard Deviation 108
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 4 hr n=6,9,5	201 ng/mL	Standard Deviation 109
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 5, 0 hr (pre-dose) n=4,7,3	29.2 ng/mL	Standard Deviation 6.67
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 0 hr (pre-dose) n=4,5,3	0 ng/mL	Standard Deviation 0
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 8 hr n=6,9,5	212 ng/mL	Standard Deviation 55.5
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 2, 24 hr n=4,5,3	31.7 ng/mL	Standard Deviation 5.42
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 8 hr n=4,5,3	189 ng/mL	Standard Deviation 63.2
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 2, 24 hr n=6,10,4	95.3 ng/mL	Standard Deviation 41.2
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 3 Day 5, 0 hr (pre-dose) n=5,6,3	29.7 ng/mL	Standard Deviation 23.3
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5, 4 hr n=5,7,5	295 ng/mL	Standard Deviation 97.9
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5, 0 hr (pre-dose) n=6,7,5	77.6 ng/mL	Standard Deviation 84.2
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 3 hr n=5,5,3	178 ng/mL	Standard Deviation 147
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 6, 24 hr n=7,8,5	72.2 ng/mL	Standard Deviation 90.5
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 5 Day 5, 0 hr (pre-dose) n=6,4,3	32.5 ng/mL	Standard Deviation 13.5
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5,1 hr n=6,6,5	155 ng/mL	Standard Deviation 123
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 6 Day 2, 0 hr (pre-dose) n=5,2,1	16.4 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 5 Day 2, 0 hr (pre-dose) n=6,4,4	49.2 ng/mL	Standard Deviation 25.1
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 2 hr n=5,5,2	144 ng/mL	Standard Deviation 200
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 6 Day 5, 0 hr (pre-dose) n=4,2,1	9.02 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 4 hr n=5,5,3	164 ng/mL	Standard Deviation 102
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 0 hr (pre-dose) n=6,7,5	0 ng/mL	Standard Deviation 0
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 4 Day 5, 0 hr (pre-dose) n=5,6,1	10.5 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 5, 2 hr n=6,7,5	324 ng/mL	Standard Deviation 112
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 0.5 hr n=6,8,5	12.8 ng/mL	Standard Deviation 21
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 4 Day 2, 0 hr (pre-dose) n=5,5,1	10.9 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 2 Day 1, 1 hr n=5,5,3	32.2 ng/mL	Standard Deviation 28.7
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 1 hr n=6,9,5	87.0 ng/mL	Standard Deviation 73.6
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 3 Day 2, 0 hr (pre-dose) n=3,4,4	39.2 ng/mL	Standard Deviation 20.5
Part 1: Ruxolitinib + Siremadlin 40 mg	Concentration Versus Time Profile for Siremadlin in Part 1	Cycle 1 Day 1, 2 hr n=6,9,5	199 ng/mL	Standard Deviation 139

Secondary

Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1

Time frame: Days 1 and 5 of Cycles 1 and 2; Day 15 of Cycle 1

Population: The pharmacokinetic (PK) analysis set included all enrolled subjects who had an evaluable PK profile.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1: Ruxolitinib + Siremadlin 20 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 2 Day 1 n=1,2,2,0,0,0,0	260 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 20 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 5 n=1,1,2,0,0,0,0	252 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 20 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2	334 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 20 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 2 Day 1 n=2,2,1,0,0,0,0	119 ng/mL	Standard Deviation 66.7
Part 1: Ruxolitinib + Siremadlin 20 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 2 Day 1 n=3,3,1,0,0,0,0	257 ng/mL	Standard Deviation 71
Part 1: Ruxolitinib + Siremadlin 20 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 5 n=2,4,1,0,0,0,0	211 ng/mL	Standard Deviation 48.8
Part 1: Ruxolitinib + Siremadlin 20 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0	310 ng/mL	Standard Deviation 131
Part 1: Ruxolitinib + Siremadlin 20 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	184 ng/mL	Standard Deviation 159
Part 1: Ruxolitinib + Siremadlin 20 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 5 n=3,3,1,0,0,0,0	152 ng/mL	Standard Deviation 55.3
Part 1: Ruxolitinib + Siremadlin 30 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0	184 ng/mL	Standard Deviation 14.8
Part 1: Ruxolitinib + Siremadlin 30 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 5 n=1,1,2,0,0,0,0	264 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 30 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 5 n=3,3,1,0,0,0,0	149 ng/mL	Standard Deviation 67.6
Part 1: Ruxolitinib + Siremadlin 30 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	209 ng/mL	Standard Deviation 20.8
Part 1: Ruxolitinib + Siremadlin 30 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 2 Day 1 n=1,2,2,0,0,0,0	337 ng/mL	Standard Deviation 70.7
Part 1: Ruxolitinib + Siremadlin 30 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 2 Day 1 n=2,2,1,0,0,0,0	165 ng/mL	Standard Deviation 29.7
Part 1: Ruxolitinib + Siremadlin 30 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 2 Day 1 n=3,3,1,0,0,0,0	176 ng/mL	Standard Deviation 66
Part 1: Ruxolitinib + Siremadlin 30 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 5 n=2,4,1,0,0,0,0	232 ng/mL	Standard Deviation 104
Part 1: Ruxolitinib + Siremadlin 40 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 2 Day 1 n=3,3,1,0,0,0,0	241 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 5 mg Cycle 1 Day 1 n=0,0,2,1,0,0,0	93.3 ng/mL	Standard Deviation 26.5
Part 1: Ruxolitinib + Siremadlin 40 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	108 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2	119 ng/mL	Standard Deviation 76.2
Part 1: Ruxolitinib + Siremadlin 40 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0	232 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 5 mg Cycle 1 Day 5 n=0,0,2,0,0,0,0	74.8 ng/mL	Standard Deviation 13.5
Part 1: Ruxolitinib + Siremadlin 40 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 5 n=3,3,1,0,0,0,0	107 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 5 n=2,4,1,0,0,0,0	180 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 5 mg Cycle 2 Day 1 n=0,0,1,0,0,0,0	82.1 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 2 Day 1 n=2,2,1,0,0,0,0	90.5 ng/mL	—
Part 1: Ruxolitinib + Siremadlin 40 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 2 Day 1 n=1,2,2,0,0,0,0	100 ng/mL	Standard Deviation 68.9
Part 1: Ruxolitinib + Siremadlin 40 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 5 n=1,1,2,0,0,0,0	172 ng/mL	Standard Deviation 96.9
Part 1: Ruxolitinib + Rineterkib 200 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	195 ng/mL	Standard Deviation 41
Part 1: Ruxolitinib + Rineterkib 200 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 25 mg Cycle 1 Day 1 n=0,0,0,1,0,0,1	46.0 ng/mL	—
Part 1: Ruxolitinib + Rineterkib 200 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 5 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0	95.4 ng/mL	—
Part 1: Ruxolitinib + Rineterkib 200 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 15 n=0,0,0,2,0,0,0	158 ng/mL	Standard Deviation 68.6
Part 1: Ruxolitinib + Rineterkib 200 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0	126 ng/mL	—
Part 1: Ruxolitinib + Rineterkib 200 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 15 n=0,0,0,3,0,0,0	369 ng/mL	Standard Deviation 83.7
Part 1: Ruxolitinib + Rineterkib 200 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 25 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0	323 ng/mL	—
Part 1: Ruxolitinib + Rineterkib 200 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 5 mg Cycle 1 Day 1 n=0,0,2,1,0,0,0	67.4 ng/mL	—
Part 1: Ruxolitinib + Rineterkib 200 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2	193 ng/mL	—
Part 1: Ruxolitinib + Rineterkib 200 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0	332 ng/mL	Standard Deviation 33.5
Part 1: Ruxolitinib + Crizanlizumab	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2	185 ng/mL	Standard Deviation 120
Part 1: Ruxolitinib + Crizanlizumab	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	191 ng/mL	—
Part 1: Ruxolitinib + Crizanlizumab	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0	221 ng/mL	—
Part 1: Ruxolitinib + Sabatolimab	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	118 ng/mL	Standard Deviation 33
Part 1: Ruxolitinib + NIS793	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2	254 ng/mL	Standard Deviation 73.5
Part 1: Ruxolitinib + NIS793	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	132 ng/mL	—
Part 1: Ruxolitinib + NIS793	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1	Ruxolitinib 25 mg Cycle 1 Day 1 n=0,0,0,1,0,0,1	224 ng/mL	—

Secondary

Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1

Time frame: Days 1 and 5 of Cycles 1 and 2 for siremadlin and Cycles 1 and 3 for crizanlizumab, sabatolimab, and NIS793; Days 1 and 15 of Cycle 1 for rineterkib

Population: The pharmacokinetic (PK) analysis set included all enrolled subjects who had an evaluable PK profile.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1: Ruxolitinib + Siremadlin 20 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	118 ng/mL	Standard Deviation 32.8
Part 1: Ruxolitinib + Siremadlin 20 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 5 n=6,7,5,0,0,0,0	161 ng/mL	Standard Deviation 78
Part 1: Ruxolitinib + Siremadlin 20 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 1 n=5,6,3,0,0,0,0	131 ng/mL	Standard Deviation 57.9
Part 1: Ruxolitinib + Siremadlin 20 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 5 n=3,5,3,0,0,0,0	103 ng/mL	Standard Deviation 34.1
Part 1: Ruxolitinib + Siremadlin 30 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 1 n=5,6,3,0,0,0,0	142 ng/mL	Standard Deviation 102
Part 1: Ruxolitinib + Siremadlin 30 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	207 ng/mL	Standard Deviation 122
Part 1: Ruxolitinib + Siremadlin 30 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 5 n=6,7,5,0,0,0,0	284 ng/mL	Standard Deviation 138
Part 1: Ruxolitinib + Siremadlin 30 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 5 n=3,5,3,0,0,0,0	193 ng/mL	Standard Deviation 95
Part 1: Ruxolitinib + Siremadlin 40 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 1 n=5,6,3,0,0,0,0	268 ng/mL	Standard Deviation 15
Part 1: Ruxolitinib + Siremadlin 40 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	290 ng/mL	Standard Deviation 56.1
Part 1: Ruxolitinib + Siremadlin 40 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 5 n=6,7,5,0,0,0,0	336 ng/mL	Standard Deviation 109
Part 1: Ruxolitinib + Siremadlin 40 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 5 n=3,5,3,0,0,0,0	228 ng/mL	Standard Deviation 58.3
Part 1: Ruxolitinib + Rineterkib 200 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	469 ng/mL	Standard Deviation 358
Part 1: Ruxolitinib + Rineterkib 200 mg	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 15 n=0,0,0,9,0,0,0	987 ng/mL	Standard Deviation 621
Part 1: Ruxolitinib + Crizanlizumab	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 3 Day 1 n=0,0,0,0,5,2,3	114000 ng/mL	Standard Deviation 56600
Part 1: Ruxolitinib + Crizanlizumab	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	114000 ng/mL	Standard Deviation 36400
Part 1: Ruxolitinib + Sabatolimab	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 3 Day 1 n=0,0,0,0,5,2,3	150 ng/mL	Standard Deviation 33.2
Part 1: Ruxolitinib + Sabatolimab	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	131 ng/mL	Standard Deviation 17.7
Part 1: Ruxolitinib + NIS793	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	439000 ng/mL	Standard Deviation 56100
Part 1: Ruxolitinib + NIS793	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 3 Day 1 n=0,0,0,0,5,2,3	743000 ng/mL	Standard Deviation 314000

Secondary

Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1

Time frame: Week 24, Week 48

Population: The full analysis set included all subjects who received any study drug.

Arm	Measure	Group	Value (NUMBER)
Part 1: Ruxolitinib + Siremadlin 20 mg	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1	Week 48	0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 20 mg	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 30 mg	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 30 mg	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1	Week 48	0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 40 mg	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1	Week 48	0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 40 mg	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + Rineterkib 200 mg	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1	Week 24	11.1 percentage of participants
Part 1: Ruxolitinib + Rineterkib 200 mg	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1	Week 48	11.1 percentage of participants
Part 1: Ruxolitinib + Crizanlizumab	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1	Week 24	16.7 percentage of participants
Part 1: Ruxolitinib + Crizanlizumab	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1	Week 48	0 percentage of participants
Part 1: Ruxolitinib + Sabatolimab	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1	Week 48	0 percentage of participants
Part 1: Ruxolitinib + Sabatolimab	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + NIS793	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + NIS793	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1	Week 48	0 percentage of participants

Secondary

Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1

Time frame: Week 24, Week 48

Population: The full analysis set included all subjects who received any study drug.

Arm	Measure	Group	Value (NUMBER)
Part 1: Ruxolitinib + Siremadlin 20 mg	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 20 mg	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1	Week 48	0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 30 mg	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 30 mg	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1	Week 48	0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 40 mg	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 40 mg	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1	Week 48	0 percentage of participants
Part 1: Ruxolitinib + Rineterkib 200 mg	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1	Week 24	11.1 percentage of participants
Part 1: Ruxolitinib + Rineterkib 200 mg	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1	Week 48	11.1 percentage of participants
Part 1: Ruxolitinib + Crizanlizumab	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + Crizanlizumab	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1	Week 48	0 percentage of participants
Part 1: Ruxolitinib + Sabatolimab	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + Sabatolimab	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1	Week 48	0 percentage of participants
Part 1: Ruxolitinib + NIS793	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + NIS793	Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1	Week 48	0 percentage of participants

Secondary

Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)

The MFSAF v4.0 questionnaire focuses on the 7 core symptoms of MF: fatigue, night sweats, pruritus, abdominal discomfort, pain under the ribs on the left side, early satiety and bone pain. Subjects record symptom severity at it worst for each of the 7 symptoms on an 11-point numeric rating scale, from 0 (absent) to 10 (worst imaginable). The Total Symptom Score (TSS) is the sum of all the scores for all 7 symptoms.

Time frame: Week 12, Week 24, Week 48

Population: The full analysis set included all subjects who received any study drug.

Arm	Measure	Group	Value (NUMBER)
Part 1: Ruxolitinib + Siremadlin 20 mg	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 48	14.3 percentage of participants
Part 1: Ruxolitinib + Siremadlin 20 mg	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 24	14.3 percentage of participants
Part 1: Ruxolitinib + Siremadlin 20 mg	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 12	42.9 percentage of participants
Part 1: Ruxolitinib + Siremadlin 30 mg	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 24	20.0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 30 mg	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 12	30.0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 30 mg	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 48	10.0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 40 mg	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 48	16.7 percentage of participants
Part 1: Ruxolitinib + Siremadlin 40 mg	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 12	16.7 percentage of participants
Part 1: Ruxolitinib + Siremadlin 40 mg	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 24	33.3 percentage of participants
Part 1: Ruxolitinib + Rineterkib 200 mg	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 24	11.1 percentage of participants
Part 1: Ruxolitinib + Rineterkib 200 mg	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 12	11.1 percentage of participants
Part 1: Ruxolitinib + Rineterkib 200 mg	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 48	0 percentage of participants
Part 1: Ruxolitinib + Crizanlizumab	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 24	16.7 percentage of participants
Part 1: Ruxolitinib + Crizanlizumab	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 12	16.7 percentage of participants
Part 1: Ruxolitinib + Crizanlizumab	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 48	0 percentage of participants
Part 1: Ruxolitinib + Sabatolimab	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 12	0 percentage of participants
Part 1: Ruxolitinib + Sabatolimab	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 48	0 percentage of participants
Part 1: Ruxolitinib + Sabatolimab	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 24	0 percentage of participants
Part 1: Ruxolitinib + NIS793	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 48	0 percentage of participants
Part 1: Ruxolitinib + NIS793	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 24	0 percentage of participants
Part 1: Ruxolitinib + NIS793	Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)	Week 12	0 percentage of participants

Secondary

Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1

Change in spleen volume measured by magnetic resonance imaging (MRI) or computed tomography (CT) from baseline.

Time frame: Week 24, Week 48

Population: The full analysis set included all subjects who received any study drug.

Arm	Measure	Group	Value (NUMBER)
Part 1: Ruxolitinib + Siremadlin 20 mg	Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1	Week 24	28.6 percentage of participants
Part 1: Ruxolitinib + Siremadlin 20 mg	Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1	Week 48	28.6 percentage of participants
Part 1: Ruxolitinib + Siremadlin 30 mg	Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1	Week 24	60.0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 30 mg	Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1	Week 48	10.0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 40 mg	Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 40 mg	Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1	Week 48	16.7 percentage of participants
Part 1: Ruxolitinib + Rineterkib 200 mg	Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1	Week 24	11.1 percentage of participants
Part 1: Ruxolitinib + Rineterkib 200 mg	Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1	Week 48	11.1 percentage of participants
Part 1: Ruxolitinib + Crizanlizumab	Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + Crizanlizumab	Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1	Week 48	0 percentage of participants
Part 1: Ruxolitinib + Sabatolimab	Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + Sabatolimab	Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1	Week 48	0 percentage of participants
Part 1: Ruxolitinib + NIS793	Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + NIS793	Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1	Week 48	0 percentage of participants

Secondary

Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1

Change in spleen volume measured by magnetic resonance imaging (MRI) or computed tomography (CT) from baseline.

Time frame: Week 24, Week 48

Population: The full analysis set included all subjects who received any study drug.

Arm	Measure	Group	Value (NUMBER)
Part 1: Ruxolitinib + Siremadlin 20 mg	Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1	Week 48	14.3 percentage of participants
Part 1: Ruxolitinib + Siremadlin 20 mg	Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1	Week 24	14.3 percentage of participants
Part 1: Ruxolitinib + Siremadlin 30 mg	Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1	Week 24	60.0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 30 mg	Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1	Week 48	10.0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 40 mg	Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + Siremadlin 40 mg	Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1	Week 48	16.7 percentage of participants
Part 1: Ruxolitinib + Rineterkib 200 mg	Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1	Week 48	0 percentage of participants
Part 1: Ruxolitinib + Rineterkib 200 mg	Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + Crizanlizumab	Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + Crizanlizumab	Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1	Week 48	0 percentage of participants
Part 1: Ruxolitinib + Sabatolimab	Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + Sabatolimab	Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1	Week 48	0 percentage of participants
Part 1: Ruxolitinib + NIS793	Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1	Week 24	0 percentage of participants
Part 1: Ruxolitinib + NIS793	Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1	Week 48	0 percentage of participants

Secondary

Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1

Time frame: Days 1 and 5 of Cycles 1 and 2; Day 15 of Cycle 1

Population: The pharmacokinetic (PK) analysis set included all enrolled subjects who had an evaluable PK profile.

Arm	Measure	Group	Value (MEDIAN)
Part 1: Ruxolitinib + Siremadlin 20 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2	0.650 hours
Part 1: Ruxolitinib + Siremadlin 20 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	0.550 hours
Part 1: Ruxolitinib + Siremadlin 20 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 2 Day 1 n=2,2,1,0,0,0,0	0.895 hours
Part 1: Ruxolitinib + Siremadlin 20 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 2 Day 1 n=3,3,1,0,0,0,0	0.980 hours
Part 1: Ruxolitinib + Siremadlin 20 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 5 n=2,4,1,0,0,0,0	0.925 hours
Part 1: Ruxolitinib + Siremadlin 20 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0	0.530 hours
Part 1: Ruxolitinib + Siremadlin 20 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 5 n=3,3,1,0,0,0,0	1.00 hours
Part 1: Ruxolitinib + Siremadlin 20 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 2 Day 1 n=1,2,2,0,0,0,0	1.05 hours
Part 1: Ruxolitinib + Siremadlin 20 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 5 n=1,1,2,0,0,0,0	0.970 hours
Part 1: Ruxolitinib + Siremadlin 30 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	0.775 hours
Part 1: Ruxolitinib + Siremadlin 30 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 5 n=3,3,1,0,0,0,0	0.980 hours
Part 1: Ruxolitinib + Siremadlin 30 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 2 Day 1 n=3,3,1,0,0,0,0	1.02 hours
Part 1: Ruxolitinib + Siremadlin 30 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 2 Day 1 n=1,2,2,0,0,0,0	1.46 hours
Part 1: Ruxolitinib + Siremadlin 30 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 2 Day 1 n=2,2,1,0,0,0,0	1.00 hours
Part 1: Ruxolitinib + Siremadlin 30 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 5 n=2,4,1,0,0,0,0	1.00 hours
Part 1: Ruxolitinib + Siremadlin 30 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0	1.54 hours
Part 1: Ruxolitinib + Siremadlin 30 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 5 n=1,1,2,0,0,0,0	0.830 hours
Part 1: Ruxolitinib + Siremadlin 40 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 2 Day 1 n=3,3,1,0,0,0,0	0.930 hours
Part 1: Ruxolitinib + Siremadlin 40 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	0.500 hours
Part 1: Ruxolitinib + Siremadlin 40 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2	1.96 hours
Part 1: Ruxolitinib + Siremadlin 40 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0	1.00 hours
Part 1: Ruxolitinib + Siremadlin 40 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 5 mg Cycle 1 Day 5 n=0,0,2,0,0,0,0	0.960 hours
Part 1: Ruxolitinib + Siremadlin 40 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 5 n=3,3,1,0,0,0,0	1.00 hours
Part 1: Ruxolitinib + Siremadlin 40 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 5 n=1,1,2,0,0,0,0	0.955 hours
Part 1: Ruxolitinib + Siremadlin 40 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 5 n=2,4,1,0,0,0,0	0.830 hours
Part 1: Ruxolitinib + Siremadlin 40 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 5 mg Cycle 2 Day 1 n=0,0,1,0,0,0,0	0.900 hours
Part 1: Ruxolitinib + Siremadlin 40 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 2 Day 1 n=2,2,1,0,0,0,0	2.00 hours
Part 1: Ruxolitinib + Siremadlin 40 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 2 Day 1 n=1,2,2,0,0,0,0	4.00 hours
Part 1: Ruxolitinib + Siremadlin 40 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 5 mg Cycle 1 Day 1 n=0,0,2,1,0,0,0	0.960 hours
Part 1: Ruxolitinib + Rineterkib 200 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	0.485 hours
Part 1: Ruxolitinib + Rineterkib 200 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 25 mg Cycle 1 Day 1 n=0,0,0,1,0,0,1	0.00 hours
Part 1: Ruxolitinib + Rineterkib 200 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 5 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0	0.500 hours
Part 1: Ruxolitinib + Rineterkib 200 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 15 n=0,0,0,2,0,0,0	1.98 hours
Part 1: Ruxolitinib + Rineterkib 200 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0	0.500 hours
Part 1: Ruxolitinib + Rineterkib 200 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 15 n=0,0,0,3,0,0,0	0.650 hours
Part 1: Ruxolitinib + Rineterkib 200 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 25 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0	0.500 hours
Part 1: Ruxolitinib + Rineterkib 200 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 5 mg Cycle 1 Day 1 n=0,0,2,1,0,0,0	0.500 hours
Part 1: Ruxolitinib + Rineterkib 200 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2	0.420 hours
Part 1: Ruxolitinib + Rineterkib 200 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0	0.450 hours
Part 1: Ruxolitinib + Crizanlizumab	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2	1.80 hours
Part 1: Ruxolitinib + Crizanlizumab	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	0.580 hours
Part 1: Ruxolitinib + Crizanlizumab	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0	1.17 hours
Part 1: Ruxolitinib + Sabatolimab	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	0.460 hours
Part 1: Ruxolitinib + NIS793	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2	2.42 hours
Part 1: Ruxolitinib + NIS793	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1	1.67 hours
Part 1: Ruxolitinib + NIS793	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1	Ruxolitinib 25 mg Cycle 1 Day 1 n=0,0,0,1,0,0,1	2.00 hours

Secondary

Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1

Time frame: Days 1 and 5 of Cycles 1 and 2 for siremadlin and Cycles 1 and 3 for crizanlizumab, sabatolimab, and NIS793; Days 1 and 15 of Cycle 1 for rineterkib

Population: The pharmacokinetic (PK) analysis set included all enrolled subjects who had an evaluable PK profile.

Arm	Measure	Group	Value (MEDIAN)
Part 1: Ruxolitinib + Siremadlin 20 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	2.52 hours
Part 1: Ruxolitinib + Siremadlin 20 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 5 n=6,7,5,0,0,0,0	3.44 hours
Part 1: Ruxolitinib + Siremadlin 20 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 1 n=5,6,3,0,0,0,0	1.95 hours
Part 1: Ruxolitinib + Siremadlin 20 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 5 n=3,5,3,0,0,0,0	3.00 hours
Part 1: Ruxolitinib + Siremadlin 30 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 1 n=5,6,3,0,0,0,0	3.92 hours
Part 1: Ruxolitinib + Siremadlin 30 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	3.00 hours
Part 1: Ruxolitinib + Siremadlin 30 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 5 n=6,7,5,0,0,0,0	2.90 hours
Part 1: Ruxolitinib + Siremadlin 30 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 5 n=3,5,3,0,0,0,0	2.93 hours
Part 1: Ruxolitinib + Siremadlin 40 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 1 n=5,6,3,0,0,0,0	2.88 hours
Part 1: Ruxolitinib + Siremadlin 40 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	3.93 hours
Part 1: Ruxolitinib + Siremadlin 40 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 5 n=6,7,5,0,0,0,0	2.87 hours
Part 1: Ruxolitinib + Siremadlin 40 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 2 Day 5 n=3,5,3,0,0,0,0	3.02 hours
Part 1: Ruxolitinib + Rineterkib 200 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	3.92 hours
Part 1: Ruxolitinib + Rineterkib 200 mg	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 15 n=0,0,0,9,0,0,0	2.50 hours
Part 1: Ruxolitinib + Crizanlizumab	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 3 Day 1 n=0,0,0,0,5,2,3	1.65 hours
Part 1: Ruxolitinib + Crizanlizumab	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	1.82 hours
Part 1: Ruxolitinib + Sabatolimab	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 3 Day 1 n=0,0,0,0,5,2,3	2.01 hours
Part 1: Ruxolitinib + Sabatolimab	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	1.84 hours
Part 1: Ruxolitinib + NIS793	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 1 Day 1 n=6,9,5,9,5,2,4	2.00 hours
Part 1: Ruxolitinib + NIS793	Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1	Cycle 3 Day 1 n=0,0,0,0,5,2,3	1.97 hours

Source: ClinicalTrials.gov · Data processed: Feb 17, 2026

Platform Study of Novel Ruxolitinib Combinations in Myelofibrosis Patients

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Masking description

Intervention model description

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1

Response Rate at the End of Cycle 6 or Cycle 8 in Part 1

Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1

Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1

Change in Spleen Length From Baseline in Part 1

Concentration Versus Time Profile for Crizanlizumab in Part 1

Concentration Versus Time Profile for NIS793 in Part 1

Concentration Versus Time Profile for Rineterkib in Part 1

Concentration Versus Time Profile for Ruxolitinib in Part 1

Concentration Versus Time Profile for Sabatolimab in Part 1

Concentration Versus Time Profile for Siremadlin in Part 1

Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1

Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1

Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1

Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1

Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)

Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1

Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1

Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1

Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1