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Clinical Trial Results:
A Phase 1/2, Open-Label, Multicenter Study of INCB000928 Administered as a Monotherapy in Participants With Anemia Due to Myelodysplastic Syndromes or Multiple Myeloma

Summary
EudraCT number	2020-002771-35
Trial protocol	FR IT
Global end of trial date	15 Aug 2024

Results information
Results version number	v1(current)
This version publication date	31 Aug 2025
First version publication date	31 Aug 2025
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

INCB 00928-105

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Incyte Corporation

Sponsor organisation address

1801 Augustine Cutoff, Wilmington, United States, 19803

Public contact

Study Director, Incyte Corporation, 1 8554633463, medinfo@incyte.com

Scientific contact

Study Director, Incyte Corporation, 1 8554633463, medinfo@incyte.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

15 Aug 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

15 Aug 2024

Was the trial ended prematurely?

Main objective of the trial

This Phase 1/2, open-label, dose-finding study was intended to evaluate the safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of zilurgisertib administered as monotherapy in participants with myelodysplastic syndromes (MDSs) or multiple myeloma (MM) who were transfusion-dependent or presented with symptomatic anemia.

Protection of trial subjects

This study was performed in accordance with ethical principles that have their origin in the Declaration of Helsinki (Brazil 2013) and conducted in adherence to the study Protocol, applicable Good Clinical Practices, and applicable laws and country-specific regulations, including WMO (Medical Research Involving Human Participants Act) and Clinical Trials Regulation (EU) No. 536/2014, in which the study was conducted.

Background therapy

Evidence for comparator

Actual start date of recruitment

19 Aug 2021

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

France: 3

Country: Number of subjects enrolled

Italy: 1

Country: Number of subjects enrolled

United States: 17

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

This study was conducted at 8 study centers in the United States, France, and Italy.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Zilurgisertib 50 mg QD

Arm description

Participants with myelodysplastic syndromes (MDS) or multiple myeloma (MM) who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 50 milligrams (mg) once daily (QD) administered as a monotherapy for up to 6 months.

Arm type

Experimental

Investigational medicinal product name

Zilurgisertib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

tablets administered once daily orally

Zilurgisertib 100 mg QD

Arm description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 100 mg QD administered as a monotherapy for up to 6 months.

Arm type

Experimental

Investigational medicinal product name

Zilurgisertib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

tablets administered once daily orally

Zilurgisertib 200 mg QD

Arm description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 200 mg QD administered as a monotherapy for up to 6 months.

Arm type

Experimental

Investigational medicinal product name

Zilurgisertib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

tablets administered once daily orally

Zilurgisertib 400 mg QD

Arm description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 400 mg QD administered as a monotherapy for up to 6 months.

Arm type

Experimental

Investigational medicinal product name

Zilurgisertib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

tablets administered once daily orally

Zilurgisertib 600 mg QD

Arm description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 600 mg QD administered as a monotherapy for up to 6 months.

Arm type

Experimental

Investigational medicinal product name

Zilurgisertib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

tablets administered once daily orally

Number of subjects in period 1	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Started	4	5	4	5	3
Completed	0	0	0	0	0
Not completed	4	5	4	5	3
Consent withdrawn by subject	1	-	2	1	-
Physician decision	-	1	-	-	-
Death	1	1	-	1	-
Study Terminated by Sponsor	1	3	2	2	3
Lost to follow-up	1	-	-	-	-
Started New Therapy; Did Not Return to Clinic	-	-	-	1	-

Baseline characteristics

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Reporting group title

Zilurgisertib 50 mg QD

Reporting group description

Reporting group title

Zilurgisertib 100 mg QD

Reporting group description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 100 mg QD administered as a monotherapy for up to 6 months.

Reporting group title

Zilurgisertib 200 mg QD

Reporting group description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 200 mg QD administered as a monotherapy for up to 6 months.

Reporting group title

Zilurgisertib 400 mg QD

Reporting group description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 400 mg QD administered as a monotherapy for up to 6 months.

Reporting group title

Zilurgisertib 600 mg QD

Reporting group description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 600 mg QD administered as a monotherapy for up to 6 months.

Reporting group values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD	Total
Number of subjects	4	5	4	5	3	21
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0
Adults (18-64 years)	0	0	0	0	0	0
From 65-84 years	4	5	3	5	3	20
85 years and over	0	0	1	0	0	1
Age Continuous
Units: years
arithmetic mean (standard deviation)	68.8 ( 4.50 )	74.6 ( 3.78 )	78.5 ( 6.19 )	74.8 ( 4.87 )	75.7 ( 6.66 )	-
Sex: Female, Male
Units: participants
Female	2	1	2	4	1	10
Male	2	4	2	1	2	11
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0
Asian	0	0	1	1	0	2
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0
Black or African American	0	0	0	1	0	1
White	1	5	3	3	3	15
More than one race	0	0	0	0	0	0
Unknown or Not Reported	3	0	0	0	0	3
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	0	0	0	0	0	0
Not Hispanic or Latino	1	5	4	3	3	16
Unknown or Not Reported	3	0	0	2	0	5

Subject analysis set title

All participants

Subject analysis set type

Full analysis

Subject analysis set description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib QD administered as a monotherapy for up to 6 months.

Subject analysis set title

Zilurgisertib 25 mg QD

Subject analysis set type

Full analysis

Subject analysis set description

Participants with myelodysplastic syndromes (MDS) or multiple myeloma (MM) who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 25 milligrams (mg) once daily (QD) administered as a monotherapy from Day 1 to Day 16.

Subject analysis sets values	All participants	Zilurgisertib 25 mg QD
Number of subjects	21	1
Age categorical
Units: Subjects
In utero	0
Preterm newborn infants (gestational age < 37 wks)	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	0
From 65-84 years	20
85 years and over	1
Age Continuous
Units: years
arithmetic mean (standard deviation)	( )	( )
Sex: Female, Male
Units: participants
Female	10
Male	11
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0
Asian	2
Native Hawaiian or Other Pacific Islander	0
Black or African American	1
White	15
More than one race	0
Unknown or Not Reported	3
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	0
Not Hispanic or Latino	16
Unknown or Not Reported	5

End points

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Reporting group title

Zilurgisertib 50 mg QD

Reporting group description

Reporting group title

Zilurgisertib 100 mg QD

Reporting group description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 100 mg QD administered as a monotherapy for up to 6 months.

Reporting group title

Zilurgisertib 200 mg QD

Reporting group description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 200 mg QD administered as a monotherapy for up to 6 months.

Reporting group title

Zilurgisertib 400 mg QD

Reporting group description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 400 mg QD administered as a monotherapy for up to 6 months.

Reporting group title

Zilurgisertib 600 mg QD

Reporting group description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 600 mg QD administered as a monotherapy for up to 6 months.

Subject analysis set title

All participants

Subject analysis set type

Full analysis

Subject analysis set description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib QD administered as a monotherapy for up to 6 months.

Subject analysis set title

Zilurgisertib 25 mg QD

Subject analysis set type

Full analysis

Subject analysis set description

Participants with myelodysplastic syndromes (MDS) or multiple myeloma (MM) who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 25 milligrams (mg) once daily (QD) administered as a monotherapy from Day 1 to Day 16.

Primary: Number of participants with any treatment-emergent adverse event (TEAE)

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End point title

Number of participants with any treatment-emergent adverse event (TEAE) ^[1]

End point description

An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. A TEAE is an AE reported for the first time or the worsening of a pre-existing event after the first dose of study drug. The Full Analysis Set-MDS was comprised of all participants with myelodysplastic syndromes (MDS) or MDS/myeloproliferative neoplasm (MPN) overlap syndromes who received at least 1 dose of zilurgisertib.

End point type

Primary

End point timeframe

up to 950 days

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not conducted for this endpoint.

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	4 ^[2]	5 ^[3]	4 ^[4]	5 ^[5]	3 ^[6]
Units: participants	4	5	4	5	2

Notes
[2] - Full Analysis Set-MDS
[3] - Full Analysis Set-MDS
[4] - Full Analysis Set-MDS
[5] - Full Analysis Set-MDS
[6] - Full Analysis Set-MDS

No statistical analyses for this end point

Primary: Number of participants with any ≥Grade 3 TEAE

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End point title

Number of participants with any ≥Grade 3 TEAE ^[7]

End point description

The severity of AEs was assessed using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to one of the following categories. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.

End point type

Primary

End point timeframe

up to 950 days

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not conducted for this endpoint.

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	4 ^[8]	5 ^[9]	4 ^[10]	5 ^[11]	3 ^[12]
Units: participants	2	3	2	2	2

Notes
[8] - Full Analysis Set-MDS
[9] - Full Analysis Set-MDS
[10] - Full Analysis Set-MDS
[11] - Full Analysis Set-MDS
[12] - Full Analysis Set-MDS

No statistical analyses for this end point

Primary: Number of participants with dose-limiting toxicities (DLTs)

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End point title

Number of participants with dose-limiting toxicities (DLTs) ^[13]

End point description

A DLT was defined as the occurrence of any protocol-defined toxicities occurring during the first study drug treatment cycle, from C1D1 up to and including Cycle 1 Day 28 (per regimen cycle schedule), except those with a clear alternative explanation (e.g., disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. The DLT Evaluable Population was comprised of all participants in the FAS Population who met the following criteria: observed for at least the first treatment cycle (i.e., 28 days); received ≥75% of doses of study treatment at the level assigned to that cohort (i.e., 21 days of treatment) or had a DLT during the first study treatment cycle; did not receive any strong or potent CYP3A4/5 inhibitor or inducer during the first study drug treatment cycle (DLT assessment period); was not part of a backfill cohort.

End point type

Primary

End point timeframe

up to Day 28

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not conducted for this endpoint.

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	4 ^[14]	3 ^[15]	4 ^[16]	3 ^[17]	2 ^[18]
Units: participants	0	0	0	0	1

Notes
[14] - DLT Evaluable Population
[15] - DLT Evaluable Population
[16] - DLT Evaluable Population
[17] - DLT Evaluable Population
[18] - DLT Evaluable Population

No statistical analyses for this end point

Primary: Maximum tolerated dose (MTD)

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End point title

Maximum tolerated dose (MTD) ^[19]

End point description

The MTD was defined as the dose at which the observed DLT rate was closest to the target DLT rate of 28% using an isotonical method that took the assumption of a monotonic dose-toxicity relationship into account. 9999=The MTD was not defined due to early termination of the study.

End point type

Primary

End point timeframe

up to Day 28

Notes
[19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not conducted for this endpoint.

End point values	All participants
Number of subjects analysed	21 ^[20]
Units: milligrams	9999

Notes
[20] - Full Analysis Set-MDS

No statistical analyses for this end point

Primary: Recommended dose for expansion (RDE)

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End point title

Recommended dose for expansion (RDE) ^[21]

End point description

RDE doses were defined as pharmacodynamically active. RDE doses were not to have exceeded the MTD defined in each treatment group. 9999=The RDE was not defined due to early termination of the study.

End point type

Primary

End point timeframe

up to Day 28

Notes
[21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not conducted for this endpoint.

End point values	All participants
Number of subjects analysed	21 ^[22]
Units: milligrams	9999

Notes
[22] - Full Analysis Set-MDS

No statistical analyses for this end point

Secondary: Percentage of participants with anemia response

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End point title

Percentage of participants with anemia response

End point description

Participants with anemia response were those with a hemoglobin (Hgb) increase of ≥1.5 grams per deciliter (g/dL) relative to baseline for any 8-week period (with each assessment meeting this requirement) during the first 24 weeks of treatment if transfusion independent at baseline. Transfusion-independent participants at baseline were those that did not receive ≥4 units of red blood cell (RBC) transfusions during the 28 days immediately preceding Cycle 1 Day 1 or did not receive ≥4 units of RBC transfusions in the 8 weeks immediately preceding Cycle 1 Day 1, for an Hgb level of <8.5 g/dL, in the absence of bleeding or treatment-induced anemia. Participants must have been on treatment for ≥8 consecutive weeks or discontinued treatment before Week 8. Only participants who were transfusion independent at baseline were analyzed. The 95% confidence interval was calculated using exact binomial distribution.

End point type

Secondary

End point timeframe

up to Week 24

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	2 ^[23]	4 ^[24]	2 ^[25]	4 ^[26]	2 ^[27]
Units: percentage of participants
number (confidence interval 95%)	0.0 (0.0 to 84.2)	0.0 (0.0 to 60.2)	0.0 (0.0 to 84.2)	0.0 (0.0 to 60.2)	0.0 (0.0 to 84.2)

Notes
[23] - Full Analysis Set-MDS
[24] - Full Analysis Set-MDS
[25] - Full Analysis Set-MDS
[26] - Full Analysis Set-MDS
[27] - Full Analysis Set-MDS

No statistical analyses for this end point

Secondary: Duration of anemia response (DoAR)

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End point title

Duration of anemia response (DoAR)

End point description

DoAR was the interval from the first onset of anemia response (AR) to the earliest date of loss of AR that persisted for ≥4 weeks or death from any cause. Participants with AR had a hemoglobin (Hgb) increase of ≥1.5 grams per deciliter (g/dL) relative to baseline for any 8-week period (with each assessment meeting this requirement) during the first 24 weeks of treatment if transfusion independent at baseline. Transfusion-independent participants at baseline were those that did not receive ≥4 units of red blood cell (RBC) transfusions during the 28 days immediately preceding Cycle 1 Day 1 or did not receive ≥4 units of RBC transfusions in the 8 weeks immediately preceding Cycle 1 Day 1, for an Hgb level of <8.5 g/dL, in the absence of bleeding or treatment-induced anemia. Participants must have been on treatment for ≥8 consecutive weeks and have discontinued treatment before Week 8. Only participants who were transfusion independent at baseline and had a response were analyzed.

End point type

Secondary

End point timeframe

up to 920 days

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	0 ^[28]	0 ^[29]	0 ^[30]	0 ^[31]	0 ^[32]
Units: days
median (standard error)	( )	( )	( )	( )	( )

Notes
[28] - Full Analysis Set-MDS
[29] - Full Analysis Set-MDS
[30] - Full Analysis Set-MDS
[31] - Full Analysis Set-MDS
[32] - Full Analysis Set-MDS

No statistical analyses for this end point

Secondary: Percentage of participants with RBC-transfusion independence (TI)

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End point title

Percentage of participants with RBC-transfusion independence (TI)

End point description

Participants with RBC-transfusion independence were defined as those who did not require any RBC transfusion for at least 8 consecutive weeks during the first 24 weeks of treatment. Only participants who were transfusion dependent at Baseline were analyzed. The 95% confidence interval was calculated using exact binomial distribution.

End point type

Secondary

End point timeframe

up to Week 24

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	2 ^[33]	1 ^[34]	2 ^[35]	1 ^[36]	1 ^[37]
Units: percentage of participants
number (confidence interval 95%)	0.0 (0.0 to 84.2)	100.0 (2.5 to 100.0)	0.0 (0.0 to 84.2)	0.0 (0.0 to 97.5)	0.0 (0.0 to 97.5)

Notes
[33] - Full Analysis Set-MDS
[34] - Full Analysis Set-MDS
[35] - Full Analysis Set-MDS
[36] - Full Analysis Set-MDS
[37] - Full Analysis Set-MDS

No statistical analyses for this end point

Secondary: Duration of RBC-transfusion independence (TI) period for participants achieving RBC-TI for at least 8 consecutive weeks during the first 24 weeks of treatment

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End point title

Duration of RBC-transfusion independence (TI) period for participants achieving RBC-TI for at least 8 consecutive weeks during the first 24 weeks of treatment

End point description

Participants with RBC-TI were defined as those who did not require any RBC transfusion for at least 8 consecutive weeks during the first 24 weeks of treatment. Only participants who were transfusion dependent at Baseline and achieved transfusion independence were analyzed. 9999=Standard error cannot be calculated for a single participant.

End point type

Secondary

End point timeframe

up to 920 days

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	0 ^[38]	1 ^[39]	0 ^[40]	0 ^[41]	0 ^[42]
Units: days
median (standard error)	( )	60 ( 9999 )	( )	( )	( )

Notes
[38] - Full Analysis Set-MDS
[39] - Full Analysis Set-MDS
[40] - Full Analysis Set-MDS
[41] - Full Analysis Set-MDS
[42] - Full Analysis Set-MDS

No statistical analyses for this end point

Secondary: Rate of red blood cell (RBC) transfusion through Weeks 12 and 24

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End point title

Rate of red blood cell (RBC) transfusion through Weeks 12 and 24

End point description

The rate of RBC transfusion was defined as the average number of RBC units per participant-month during the treatment period. Only participants who were on treatment for at least 78 days were included in the analysis.

End point type

Secondary

End point timeframe

Weeks 12 and 24

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	4 ^[43]	5 ^[44]	4 ^[45]	5 ^[46]	3 ^[47]
Units: RBC units per participant-month
arithmetic mean (standard deviation)	2.53 ( 1.955 )	1.34 ( 0.948 )	3.01 ( 2.955 )	2.71 ( 2.232 )	1.19 ( 2.067 )

Notes
[43] - Full Analysis Set-MDS
[44] - Full Analysis Set-MDS
[45] - Full Analysis Set-MDS
[46] - Full Analysis Set-MDS
[47] - Full Analysis Set-MDS

No statistical analyses for this end point

Secondary: The largest increase from baseline in the mean Hgb values over any rolling 8-week treatment period during the first 24 weeks of treatment

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End point title

The largest increase from baseline in the mean Hgb values over any rolling 8-week treatment period during the first 24 weeks of treatment

End point description

Baseline Hgb was measured up to 8 weeks prior to the first dose administration of zilurgisertib. The baseline Hgb was defined as the average of all eligible Hgb assessments. The Hgb assessment(s) within the window from the date received RBC transfusion+1 day to the date received RBC transfusion+14 days that didn’t trigger another transfusion were excluded. Participants were included in the mean change from baseline in hemoglobin value analysis if the participant was in the FAS and met both of the following criteria: a. was on treatment for more than 8 weeks; b. had ≥1 valid post-baseline Hgb assessment(s).

End point type

Secondary

End point timeframe

up to Week 24

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	3 ^[48]	4 ^[49]	3 ^[50]	5 ^[51]	3 ^[52]
Units: grams per liter
arithmetic mean (standard deviation)	2.19 ( 2.782 )	9.73 ( 2.842 )	2.51 ( 3.681 )	4.92 ( 10.240 )	6.59 ( 4.229 )

Notes
[48] - Full Analysis Set-MDS
[49] - Full Analysis Set-MDS
[50] - Full Analysis Set-MDS
[51] - Full Analysis Set-MDS
[52] - Full Analysis Set-MDS

No statistical analyses for this end point

Secondary: Overall response rate (ORR) in MDS participants

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End point title

Overall response rate (ORR) in MDS participants

End point description

ORR was defined as the percentage of participants with complete response (CR) or partial response (PR). For MDS, CR: bone marrow with ≤5% myeloblasts with normal maturation of all cell lines; HgB ≥11 g/dl, neutrophils ≥1.0x10^9/Liter (L), platelets ≥100x10^9/L, and no blasts in the peripheral blood. For MDS, PR: all CR criteria, but bone marrow blasts decreased by ≥50% over pretreatment but still >5%; cellularity and morphology not relevant. For MDS/MPN overlap syndromes, CR: bone marrow with ≤5% myeloblasts; no osteomyelofibrosis or ≤Grade 1 fibrosis; white blood cells ≤10X10^9 cells/L, HgB ≥11 g/dL, platelets ≥100x10^9/L/≤450x10^9/L, neutrophils ≥1.0x10^9/L, no blasts, neutrophil precursors reduced to ≤2%, monocytes ≤1x10^9/L in peripheral blood; complete resolution of medullary disease. For MDS/MPN overlap syndromes, PR: normalization of peripheral counts and hepatosplenomegaly with bone marrow blasts reduced by 50%, but remaining >5% of cellularity.

End point type

Secondary

End point timeframe

up to 920 days

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	4 ^[53]	4 ^[54]	3 ^[55]	5 ^[56]	3 ^[57]
Units: percentage of participants
number (confidence interval 95%)	0.0 (0.0 to 60.2)	0.0 (0.0 to 60.2)	0.0 (0.0 to 70.8)	0.0 (0.0 to 52.2)	0.0 (0.0 to 70.8)

Notes
[53] - Full Analysis Set-MDS only. MDS/MPN overlap syndromes were excluded.
[54] - Full Analysis Set-MDS only. MDS/MPN overlap syndromes were excluded.
[55] - Full Analysis Set-MDS only. MDS/MPN overlap syndromes were excluded.
[56] - Full Analysis Set-MDS only. MDS/MPN overlap syndromes were excluded.
[57] - Full Analysis Set-MDS only. MDS/MPN overlap syndromes were excluded.

No statistical analyses for this end point

Secondary: Percentage of MDS participants with an event of progression or death

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End point title

Percentage of MDS participants with an event of progression or death

End point description

Participants with MDS/MPN overlap syndromes were excluded from analysis. Data have been reported as the percentage of participants with an event of progression or death rather than median PFS (the interval from the first dose of study drug until the first documented progression or death) because 2 participants had an event of PFS or death. It was pre-specified in the SAP that the number of MDS participants with documented progression or death was to be summarized.

End point type

Secondary

End point timeframe

up to 920 days

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	4 ^[58]	4 ^[59]	3 ^[60]	5 ^[61]	3 ^[62]
Units: percentage of participants
number (not applicable)	25.0	0.0	0.0	20.0	0.0

Notes
[58] - Full Analysis Set-MDS only
[59] - Full Analysis Set-MDS only
[60] - Full Analysis Set-MDS only
[61] - Full Analysis Set-MDS only
[62] - Full Analysis Set-MDS only

No statistical analyses for this end point

Secondary: Percentage of participants with an event of leukemia or death

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End point title

Percentage of participants with an event of leukemia or death

End point description

Data have been reported as the percentage of participants with an event of leukemia or death rather than LFS (the interval from the first dose of study drug until the first documented leukemia transformation or death from any cause) because 3 participants had an event of leukemia or death. It was pre-specified in the SAP that the number of participants with leukemia transformation or death was to be summarized.

End point type

Secondary

End point timeframe

up to 920 days

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	4 ^[63]	5 ^[64]	4 ^[65]	5 ^[66]	3 ^[67]
Units: percentage of participants
number (not applicable)	25.0	20.0	0.0	20.0	0.0

Notes
[63] - Full Analysis Set-MDS
[64] - Full Analysis Set-MDS
[65] - Full Analysis Set-MDS
[66] - Full Analysis Set-MDS
[67] - Full Analysis Set-MDS

No statistical analyses for this end point

Secondary: ORR in multiple myeloma (MM) participants

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End point title

ORR in multiple myeloma (MM) participants

End point description

ORR was defined as the percentage of participants with stringent CR, CR, very good PR, and PR.

End point type

Secondary

End point timeframe

up to 920 days

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	0 ^[68]	0 ^[69]	0 ^[70]	0 ^[71]	0 ^[72]
Units: percentage of participants
number (confidence interval 95%)	( to )	( to )	( to )	( to )	( to )

Notes
[68] - Full Analysis Set. No participants with MM were enrolled.
[69] - Full Analysis Set. No participants with MM were enrolled.
[70] - Full Analysis Set. No participants with MM were enrolled.
[71] - Full Analysis Set. No participants with MM were enrolled.
[72] - Full Analysis Set. No participants with MM were enrolled.

No statistical analyses for this end point

Secondary: PFS in MM participants

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End point title

PFS in MM participants

End point description

PFS was defined as the interval from the first dose of study drug until the first documented progression or death.

End point type

Secondary

End point timeframe

up to 920 days

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	0 ^[73]	0 ^[74]	0 ^[75]	0 ^[76]	0 ^[77]
Units: months
median (confidence interval 95%)	( to )	( to )	( to )	( to )	( to )

Notes
[73] - Full Analysis Set. No participants with MM were enrolled.
[74] - Full Analysis Set. No participants with MM were enrolled.
[75] - Full Analysis Set. No participants with MM were enrolled.
[76] - Full Analysis Set. No participants with MM were enrolled.
[77] - Full Analysis Set. No participants with MM were enrolled.

No statistical analyses for this end point

Secondary: Cmax of zilurgisertib

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End point title

Cmax of zilurgisertib

End point description

Cmax was defined as the maximum concentration of zilurgisertib. Analysis was conducted in the Pharmacokinetic (PK) Evaluable Population, comprised of all participants who received at least 1 dose of zilurgisertib and provided at least 1 postdose plasma sample (1 PK measurement). Only participants with available data were analyzed. One participant who was supposed to receive 100 mg actually received 25 mg. 7777=One participant did not have any PK data; 2 participants had values above the upper limit of quantification, meaning data for PK parameters could not be determined. 8888=Standard deviation was not calculated for a single participant. 9999=No participants were analyzed in this group at this time point.

End point type

Secondary

End point timeframe

Days 1 and 15 of Cycle 1: pre-dose; 2, 4, and 6 hours post-dose

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD	Zilurgisertib 25 mg QD
Number of subjects analysed	4 ^[78]	4 ^[79]	4 ^[80]	4 ^[81]	3 ^[82]	1 ^[83]
Units: nanomolar
arithmetic mean (standard deviation)
Cycle 1 Day 1, n=4, 4, 4, 4, 3, 1	181 ( 80.4 )	249 ( 100 )	569 ( 291 )	1950 ( 642 )	7777 ( 7777 )	79.9 ( 8888 )
Cycle 1 Day 15, n=4, 4, 4, 2, 3, 0	350 ( 131 )	636 ( 330 )	1360 ( 613 )	2620 ( 4620 )	7777 ( 7777 )	9999 ( 9999 )

Notes
[78] - PK Evaluable Population
[79] - PK Evaluable Population
[80] - PK Evaluable Population
[81] - PK Evaluable Population
[82] - PK Evaluable Population
[83] - PK Evaluable Population

No statistical analyses for this end point

Secondary: tmax of zilurgisertib

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End point title

tmax of zilurgisertib

End point description

tmax was defined as the time to the maximum observed concentration of zilurgisertib. Only participants with available data were analyzed. 7777=One participant did not have any PK data; 2 participants had values above the upper limit of quantification, meaning data for PK parameters could not be determined. -8888, 8888=Standard deviation was not calculated for a single participant. 9999=No participants were analyzed in this group at this time point.

End point type

Secondary

End point timeframe

Days 1 and 15 of Cycle 1: pre-dose; 2, 4, and 6-8 hours post-dose

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD	Zilurgisertib 25 mg QD
Number of subjects analysed	4 ^[84]	4 ^[85]	4 ^[86]	4 ^[87]	3 ^[88]	1 ^[89]
Units: hours
median (full range (min-max))
Cycle 1 Day 1, n=4, 4, 4, 4, 3, 1	2.0 (2.0 to 4.0)	2.0 (2.0 to 2.0)	3.0 (2.0 to 4.0)	2.0 (2.0 to 2.0)	7777 (7777 to 7777)	2.0 (-8888 to 8888)
Cycle 1 Day 15, n=4, 4, 4, 2, 3, 0	2.0 (2.0 to 6.0)	2.0 (2.0 to 2.0)	3.0 (2.0 to 6.0)	2.0 (2.0 to 4.0)	7777 (7777 to 7777)	9999 (9999 to 9999)

Notes
[84] - PK Evaluable Population
[85] - PK Evaluable Population
[86] - PK Evaluable Population
[87] - PK Evaluable Population
[88] - PK Evaluable Population
[89] - PK Evaluable Population

No statistical analyses for this end point

Secondary: AUClast of zilurgisertib

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End point title

AUClast of zilurgisertib

End point description

AUClast was defined as the area under the plasma concentration-time curve from time 0 to the last quantifiable measurable plasma concentration of zilurgisertib. Only participants with available data were analyzed. One participant who was supposed to receive 100 mg actually received 25 mg. 7777=One participant did not have any PK data; 2 participants had values above the upper limit of quantification, meaning data for PK parameters could not be determined. 8888=Standard deviation was not calculated for a single participant. 9999=No participants were analyzed in this group at this time point.

End point type

Secondary

End point timeframe

Days 1 and 15 of Cycle 1: pre-dose; 2, 4, and 6-8 hours post-dose

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD	Zilurgisertib 25 mg QD
Number of subjects analysed	4 ^[90]	4 ^[91]	4 ^[92]	4 ^[93]	3 ^[94]	1 ^[95]
Units: nanomolar x hour
arithmetic mean (standard deviation)
Cycle 1 Day 1, n=4, 4, 4, 4, 3, 1	749 ( 312 )	1070 ( 471 )	2540 ( 1150 )	8050 ( 2680 )	7777 ( 7777 )	343 ( 8888 )
Cycle 1 Day 14, n=4, 4, 4, 2, 3, 0	1890 ( 749 )	3090 ( 1620 )	6850 ( 3050 )	12300 ( 26100 )	7777 ( 7777 )	9999 ( 9999 )

Notes
[90] - PK Evaluable Population
[91] - PK Evaluable Population
[92] - PK Evaluable Population
[93] - PK Evaluable Population
[94] - PK Evaluable Population
[95] - PK Evaluable Population

No statistical analyses for this end point

Secondary: Percentage change in hepcidin from Cycle 1 Day 15 to Cycle 7 Day 1

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End point title

Percentage change in hepcidin from Cycle 1 Day 15 to Cycle 7 Day 1

End point description

Percentage change was calculated as the ([post-baseline value minus the baseline value] / [baseline value]) * 100. Analysis was conducted in the Pharmacodynamic (PD) Evaluable Population, comprised all participants who received at least 1 dose of zilurgisertib and provided at least 1 plasma/serum sample (1 PD measurement).

End point type

Secondary

End point timeframe

from Cycle 1 Day 15 to Cycle 7 Day 1

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	4 ^[96]	4 ^[97]	4 ^[98]	5 ^[99]	3 ^[100]
Units: percentage
arithmetic mean (standard deviation)	-24.53 ( 41.69 )	-16.25 ( 47.06 )	-11.25 ( 39.97 )	-59.02 ( 32.35 )	-63.79 ( 44.23 )

Notes
[96] - PD Evaluable Population
[97] - PD Evaluable Population
[98] - PD Evaluable Population
[99] - PD Evaluable Population
[100] - PD Evaluable Population

No statistical analyses for this end point

Secondary: Change from Baseline in ferritin

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End point title

Change from Baseline in ferritin

End point description

Change from Baseline (CFB) was calculated as the post-Baseline value minus the Baseline value. Only participants with available data were analyzed. 9999=Standard deviation was not calculated for a single participant. 8888=Data were not collected in this treatment group at this time point.

End point type

Secondary

End point timeframe

Baseline; Cycle 1 Day 8; Cycle 1 Day 15; Cycles 2, 3, 4, 5, 6, and 7 Day 1

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	4 ^[101]	5 ^[102]	4 ^[103]	5 ^[104]	3 ^[105]
Units: nanograms per milliliter
arithmetic mean (standard deviation)
Baseline, n=4, 5, 4, 5, 3	1022.35 ( 634.096 )	930.18 ( 697.078 )	2092.25 ( 1220.166 )	2034.42 ( 1329.794 )	1469.00 ( 1191.873 )
CFB at Cycle 1 Day 8, n=3, 5, 4, 3, 2	47.67 ( 43.501 )	-65.24 ( 57.388 )	203.25 ( 523.789 )	-98.83 ( 567.584 )	-110.00 ( 24.042 )
CFB at Cycle 1 Day 15, n=2, 3, 4, 3, 2	292.00 ( 161.220 )	17.30 ( 31.109 )	67.50 ( 140.950 )	-109.77 ( 98.223 )	-96.00 ( 56.569 )
CFB at Cycle 2 Day 1, n=4, 3, 4, 3, 2	101.65 ( 245.814 )	70.03 ( 76.619 )	154.50 ( 53.658 )	-92.87 ( 364.312 )	135.00 ( 200.818 )
CFB at Cycle 3 Day 1, n=4, 3, 4, 3, 3	307.58 ( 709.602 )	-6.70 ( 46.054 )	532.00 ( 833.804 )	353.77 ( 314.682 )	-383.00 ( 536.324 )
CFB at Cycle 4 Day 1, n=3, 2, 4, 5, 2	409.83 ( 689.052 )	-21.15 ( 48.295 )	875.00 ( 649.850 )	619.00 ( 275.281 )	-153.50 ( 82.731 )
CFB at Cycle 5 Day 1, n=3, 1, 4, 4, 2	349.00 ( 680.559 )	172.00 ( 9999 )	574.00 ( 394.335 )	516.10 ( 502.323 )	-106.50 ( 211.425 )
CFB at Cycle 6 Day 1, n=3, 2, 3, 2, 0	297.67 ( 614.180 )	488.50 ( 152.028 )	347.33 ( 362.417 )	442.15 ( 264.246 )	8888 ( 8888 )
CFB at Cycle 7 Day 1, n=2, 1, 3, 2, 0	365.50 ( 658.316 )	971.00 ( 9999 )	315.33 ( 222.172 )	507.35 ( 64.559 )	8888 ( 8888 )

Notes
[101] - Full Analysis Set-MDS
[102] - Full Analysis Set-MDS
[103] - Full Analysis Set-MDS
[104] - Full Analysis Set-MDS
[105] - Full Analysis Set-MDS

No statistical analyses for this end point

Secondary: Change from Baseline in hemoglobin at the end of treatment

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End point title

Change from Baseline in hemoglobin at the end of treatment

End point description

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only participants with available data were analyzed.

End point type

Secondary

End point timeframe

up to 950 days

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	4 ^[106]	5 ^[107]	4 ^[108]	5 ^[109]	3 ^[110]
Units: grams per liter
arithmetic mean (standard deviation)
Baseline, n=4, 5, 4, 5, 3	77.7750 ( 5.83688 )	75.7200 ( 4.00899 )	74.9354 ( 5.98330 )	74.6767 ( 7.94708 )	79.4139 ( 4.14997 )
CFB at end of treatment, n=2, 3, 2, 3, 3	-1.7500 ( 4.59619 )	10.1333 ( 12.87685 )	4.0182 ( 7.61104 )	16.9556 ( 12.34055 )	69.6667 ( 10.40833 )

Notes
[106] - Full Analysis Set-MDS
[107] - Full Analysis Set-MDS
[108] - Full Analysis Set-MDS
[109] - Full Analysis Set-MDS
[110] - Full Analysis Set-MDS

No statistical analyses for this end point

Secondary: Ctrough of zilurgisertib

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End point title

Ctrough of zilurgisertib

End point description

Ctrough was defined as the lowest concentration of zilurgisertib. Only participants with available data were analyzed. 7777=One participant did not have any PK data; 2 participants had values above the upper limit of quantification, meaning data for PK parameters could not be determined.

End point type

Secondary

End point timeframe

Day 15 of Cycle 1: pre-dose; 2, 4, and 6-8 hours post-dose

End point values	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Zilurgisertib 200 mg QD	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD
Number of subjects analysed	4 ^[111]	4 ^[112]	4 ^[113]	2 ^[114]	3 ^[115]
Units: nanomolar
arithmetic mean (standard deviation)	214 ( 91.8 )	304 ( 175 )	619 ( 241 )	981 ( 3130 )	7777 ( 7777 )

Notes
[111] - PK Evaluable Population
[112] - PK Evaluable Population
[113] - PK Evaluable Population
[114] - PK Evaluable Population
[115] - PK Evaluable Population

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

up to 950 days

Adverse event reporting additional description

Analysis was conducted in the Full Analysis Set-MDS, comprised of all participants with myelodysplastic syndromes (MDS) or MDS/myeloproliferative neoplasm (MPN) overlap syndromes who received at least 1 dose of zilurgisertib.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Zilurgisertib 50 mg QD

Reporting group description

Reporting group title

Zilurgisertib 100 mg QD

Reporting group description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 100 mg QD administered as a monotherapy for up to 6 months.

Reporting group title

Total

Reporting group description

Total

Reporting group title

Zilurgisertib 400 mg QD

Reporting group description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 400 mg QD administered as a monotherapy for up to 6 months.

Reporting group title

Zilurgisertib 600 mg QD

Reporting group description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 600 mg QD administered as a monotherapy for up to 6 months.

Reporting group title

Zilurgisertib 200 mg QD

Reporting group description

Participants with MDS or MM who were transfusion dependent or presented with symptomatic anemia received oral zilurgisertib 200 mg QD administered as a monotherapy for up to 6 months.

Serious adverse events	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Total	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD	Zilurgisertib 200 mg QD
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 4 (50.00%)	1 / 5 (20.00%)	7 / 21 (33.33%)	2 / 5 (40.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)
number of deaths (all causes)	1	1	3	1	0	0
number of deaths resulting from adverse events	1	0	1	0	0	0
Vascular disorders
Hypotension
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiac failure
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Syncope
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	2 / 21 (9.52%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 3	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
COVID-19
subjects affected / exposed	1 / 4 (25.00%)	1 / 5 (20.00%)	2 / 21 (9.52%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia pseudomonal
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Zilurgisertib 50 mg QD	Zilurgisertib 100 mg QD	Total	Zilurgisertib 400 mg QD	Zilurgisertib 600 mg QD	Zilurgisertib 200 mg QD
Total subjects affected by non serious adverse events
subjects affected / exposed	4 / 4 (100.00%)	5 / 5 (100.00%)	20 / 21 (95.24%)	5 / 5 (100.00%)	2 / 3 (66.67%)	4 / 4 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Vascular neoplasm
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Vascular disorders
Hypotension
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
General disorders and administration site conditions
Chills
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	2 / 21 (9.52%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	2	1	0	0
Cyst
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0	0
Fatigue
subjects affected / exposed	1 / 4 (25.00%)	1 / 5 (20.00%)	4 / 21 (19.05%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	4	2	0	0
Hyperthermia
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	0
Influenza like illness
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	2	0	0	0
Malaise
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	3	0	3	0	0	0
Oedema peripheral
subjects affected / exposed	2 / 4 (50.00%)	1 / 5 (20.00%)	6 / 21 (28.57%)	2 / 5 (40.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)
occurrences all number	2	1	6	2	1	0
Pyrexia
subjects affected / exposed	1 / 4 (25.00%)	1 / 5 (20.00%)	2 / 21 (9.52%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	2	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 4 (25.00%)	1 / 5 (20.00%)	2 / 21 (9.52%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	2	0	0	0
Dyspnoea
subjects affected / exposed	1 / 4 (25.00%)	1 / 5 (20.00%)	3 / 21 (14.29%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences all number	1	1	3	0	0	1
Hiccups
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	0
Epistaxis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1	0	0	1
Rhinitis allergic
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Upper-airway cough syndrome
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Psychiatric disorders
Confusional state
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Insomnia
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0	0
Amylase increased
subjects affected / exposed	0 / 4 (0.00%)	2 / 5 (40.00%)	3 / 21 (14.29%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	3	5	0	0	2
Aspartate aminotransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0	0
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1	0	0	1
Blood bilirubin increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1	0	0	1
Blood creatinine increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1	0	0	1
Blood phosphorus increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1	0	0	1
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	3 / 21 (14.29%)	0 / 5 (0.00%)	1 / 3 (33.33%)	2 / 4 (50.00%)
occurrences all number	0	0	6	0	2	4
Lipase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	2	0	0	2
Neutrophil count decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)
occurrences all number	0	0	2	0	2	0
Serum ferritin increased
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Weight increased
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	0
Injury, poisoning and procedural complications
Bankart lesion
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Contusion
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	0
Fall
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0	0
Limb injury
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Joint injury
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Cardiac disorders
Arrhythmia
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Palpitations
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	2	0	0	0
Nervous system disorders
Dysgeusia
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Dizziness
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	3 / 21 (14.29%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences all number	1	0	3	1	0	1
Blood and lymphatic system disorders
Hypofibrinogenaemia
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	0
Neutropenia
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	2 / 21 (9.52%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)
occurrences all number	0	1	2	0	1	0
Thrombocytopenia
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	2 / 21 (9.52%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)
occurrences all number	0	1	2	0	1	0
Ear and labyrinth disorders
External ear pain
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Gastrointestinal disorders
Abdominal pain lower
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	2	0	0	0
Abdominal pain
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	3 / 21 (14.29%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)
occurrences all number	0	1	3	1	1	0
Colitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1	0	0	1
Constipation
subjects affected / exposed	1 / 4 (25.00%)	1 / 5 (20.00%)	3 / 21 (14.29%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences all number	3	1	5	0	0	1
Diarrhoea
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	3 / 21 (14.29%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences all number	3	0	5	1	0	1
Haemorrhoids
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	0
Gingival bleeding
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	0
Odynophagia
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	0
Nausea
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	4 / 21 (19.05%)	1 / 5 (20.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)
occurrences all number	1	0	5	1	1	2
Stomatitis
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Vomiting
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	2 / 21 (9.52%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)
occurrences all number	0	1	2	0	1	0
Hepatobiliary disorders
Hyperbilirubinaemia
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Jaundice
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	3 / 21 (14.29%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	3	2	0	0
Dry skin
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 21 (9.52%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	2	2	0	0
Ingrowing nail
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Skin lesion
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Pruritus
subjects affected / exposed	1 / 4 (25.00%)	1 / 5 (20.00%)	3 / 21 (14.29%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	3	1	0	0
Renal and urinary disorders
Haematuria
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0	0
Renal colic
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	2	0	0	0
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	2 / 21 (9.52%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	2	1	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Back pain
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	2 / 21 (9.52%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	2	1	0	0
Joint range of motion decreased
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Myalgia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	1	0
Pain in extremity
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1	0	0	1
Tendonitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0	0
Infections and infestations
COVID-19 pneumonia
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
COVID-19
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	0
Diverticulitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1	0	0	1
Mastitis
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	0
Otitis externa
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Pneumonia
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0
Urinary tract infection
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	4 / 21 (19.05%)	1 / 5 (20.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)
occurrences all number	0	1	6	1	0	4
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 21 (9.52%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)
occurrences all number	0	0	2	1	1	0
Hyperphosphataemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	3 / 21 (14.29%)	2 / 5 (40.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	3	2	0	1
Hypokalaemia
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	2 / 21 (9.52%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	1	3	0	0	2
Iron deficiency
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

17 Nov 2020

The overall rationale for this amendment was to implement changes based on Health Authority comments and requests.

08 Apr 2021

The overall rationale for this amendment was to implement changes and clarifications to the protocol.

22 Dec 2021

The rationale for this amendment was to implement changes to clarify the dose-escalation scheme.

20 Dec 2022

The rationale for this amendment was to implement changes to clarify the dose-expansion scheme and to allow a more complete exploration of the safety and efficacy of 1 or more recommended doses for expansion (RDE[s]).

06 Dec 2023

The primary purpose of the amendment was to reduce the investigational sampling for participants on the study following the Sponsor's strategic decision to stop further recruitment. Participants were followed for efficacy and safety while on study but no further pharmacokinetic (PK) or pharmacodynamic (PD)/translational sampling occurred. Unnecessary assessments or samples were also removed.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

The sponsor terminated study enrollment as a strategic decision. Due to early study termination, no participants were enrolled in the expansion stage of the study.

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Clinical trials

Clinical Trial Results: A Phase 1/2, Open-Label, Multicenter Study of INCB000928 Administered as a Monotherapy in Participants With Anemia Due to Myelodysplastic Syndromes or Multiple Myeloma

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of participants with any treatment-emergent adverse event (TEAE)

Primary: Number of participants with any treatment-emergent adverse event (TEAE)

Primary: Number of participants with any ≥Grade 3 TEAE

Primary: Number of participants with any ≥Grade 3 TEAE

Primary: Number of participants with dose-limiting toxicities (DLTs)

Primary: Number of participants with dose-limiting toxicities (DLTs)

Primary: Maximum tolerated dose (MTD)

Primary: Maximum tolerated dose (MTD)

Primary: Recommended dose for expansion (RDE)

Primary: Recommended dose for expansion (RDE)

Secondary: Percentage of participants with anemia response

Secondary: Percentage of participants with anemia response

Secondary: Duration of anemia response (DoAR)

Secondary: Duration of anemia response (DoAR)

Secondary: Percentage of participants with RBC-transfusion independence (TI)

Secondary: Percentage of participants with RBC-transfusion independence (TI)

Secondary: Duration of RBC-transfusion independence (TI) period for participants achieving RBC-TI for at least 8 consecutive weeks during the first 24 weeks of treatment

Secondary: Duration of RBC-transfusion independence (TI) period for participants achieving RBC-TI for at least 8 consecutive weeks during the first 24 weeks of treatment

Secondary: Rate of red blood cell (RBC) transfusion through Weeks 12 and 24

Secondary: Rate of red blood cell (RBC) transfusion through Weeks 12 and 24

Secondary: The largest increase from baseline in the mean Hgb values over any rolling 8-week treatment period during the first 24 weeks of treatment

Secondary: The largest increase from baseline in the mean Hgb values over any rolling 8-week treatment period during the first 24 weeks of treatment

Secondary: Overall response rate (ORR) in MDS participants

Secondary: Overall response rate (ORR) in MDS participants

Secondary: Percentage of MDS participants with an event of progression or death

Secondary: Percentage of MDS participants with an event of progression or death

Secondary: Percentage of participants with an event of leukemia or death

Secondary: Percentage of participants with an event of leukemia or death

Secondary: ORR in multiple myeloma (MM) participants

Secondary: ORR in multiple myeloma (MM) participants

Secondary: PFS in MM participants

Secondary: PFS in MM participants

Secondary: Cmax of zilurgisertib

Secondary: Cmax of zilurgisertib

Secondary: tmax of zilurgisertib

Secondary: tmax of zilurgisertib

Secondary: AUClast of zilurgisertib

Secondary: AUClast of zilurgisertib

Secondary: Percentage change in hepcidin from Cycle 1 Day 15 to Cycle 7 Day 1

Secondary: Percentage change in hepcidin from Cycle 1 Day 15 to Cycle 7 Day 1

Secondary: Change from Baseline in ferritin

Secondary: Change from Baseline in ferritin

Secondary: Change from Baseline in hemoglobin at the end of treatment

Secondary: Change from Baseline in hemoglobin at the end of treatment

Secondary: Ctrough of zilurgisertib

Secondary: Ctrough of zilurgisertib

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Phase 1/2, Open-Label, Multicenter Study of INCB000928 Administered as a Monotherapy in Participants With Anemia Due to Myelodysplastic Syndromes or Multiple Myeloma