Trial Outcomes & Findings for Study to Investigate the Safety and Clinical Activity of GSK3326595 and Other Agents to Treat Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) (NCT NCT03614728)

Last Updated: 2023-02-06

Results Overview

CBR is defined as the percentage of participants achieving a complete remission (CR), complete marrow remission (mCR), partial remission (PR), stable disease (SD) lasting at least 8 weeks, or hematologic improvement (HI), per International Working Group (IWG) criteria, where CR=Bone marrow:\<=5 percent(%) myeloblasts with normal maturation of all cell lines; PR=Bone marrow blasts decreased by \>=50% over pre-treatment but still \>5%; mCR=Bone marrow: \<=5% myeloblasts and decrease by \>=50% over pre-treatment; SD= Failure to achieve at least PR, but no evidence of progression \>8 weeks; HI=Erythroid (E): hemoglobin increase of \>1.5 grams per deciliter (g/dL), HI-Platelet: increase of \>30,000/milliliter (mL) (starting with \>20,000/mL) and increase from \<20,000/mL to \>20,000/mL by \>100%; HI-Neutrophil: increase of \>100% and \>500/microliter. Percentage values are rounded off.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

30 participants

Primary outcome timeframe

Up to 30.8 months

Results posted on

2023-02-06

Participant Flow

This was a 2-part study in participants with myeloid malignancies. Part 1 determined the clinical activity of GSK3326595 as monotherapy. Part 2 composed of a dose escalation and dose expansion cohorts to evaluate safety and clinical activity of GSK3326595 in combination with 5-Azacitidine

A total 30 participants were enrolled in Part 1. Part 2 was terminated early following a review of clinical data collected across the GSK3326595 clinical development program. Hence, no participants were enrolled in Part 2. The decision to terminate the study was not related to new safety concerns or to a change in the benefit risk profile of GSK3326595 .

Participant milestones

Participant milestones
Measure	Part 1: GSK3326595 400 mg Participants received GSK3326595 400 milligram (mg), tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1 (Up to 30.8 Months) STARTED	13	17
Part 1 (Up to 30.8 Months) COMPLETED	12	16
Part 1 (Up to 30.8 Months) NOT COMPLETED	1	1
Part 2 (Up to 3 Years and 2 Months) STARTED	0	0
Part 2 (Up to 3 Years and 2 Months) COMPLETED	0	0
Part 2 (Up to 3 Years and 2 Months) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: GSK3326595 400 mg Participants received GSK3326595 400 milligram (mg), tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 2-Dose Escalation: GSK3326595+5-Azacitidine Participants were planned to receive GSK3326595 in combination with 5-Azacitidine in dose escalation cohort during Part 2 of the study.	Part 2-Dose Expansion: GSK3326595+5-Azacitidine Participants were planned to receive GSK3326595 in combination with 5-Azacitidine in dose expansion cohort during Part 2 of the study.
Part 1 (Up to 30.8 Months) Study Terminated By Sponsor	1	0	0	0
Part 1 (Up to 30.8 Months) Physician Decision	0	1	0	0

Baseline Characteristics

Study to Investigate the Safety and Clinical Activity of GSK3326595 and Other Agents to Treat Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: GSK3326595 400 mg n=13 Participants Participants received GSK3326595 400 milligram (mg), tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=17 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 2-Dose Escalation: GSK3326595+5-Azacitidine Participants were planned to receive GSK3326595 in combination with 5-Azacitidine in dose escalation cohort during Part 2 of the study.	Part 2-Dose Expansion: GSK3326595+5-Azacitidine Participants were planned to receive GSK3326595 in combination with 5-Azacitidine in dose expansion cohort during Part 2 of the study.	Total n=30 Participants Total of all reporting groups
Age, Continuous	70.2 Years STANDARD_DEVIATION 9.25 • n=5 Participants	72.8 Years STANDARD_DEVIATION 9.61 • n=7 Participants	—	—	71.7 Years STANDARD_DEVIATION 9.38 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	—	—	7 Participants n=21 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	13 Participants n=7 Participants	—	—	23 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants	0 Participants n=7 Participants	—	—	3 Participants n=21 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	—	—	1 Participants n=21 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	—	—	1 Participants n=21 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	8 Participants n=5 Participants	14 Participants n=7 Participants	—	—	22 Participants n=21 Participants
Race/Ethnicity, Customized Mixed Race	0 Participants n=5 Participants	1 Participants n=7 Participants	—	—	1 Participants n=21 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	2 Participants n=7 Participants	—	—	2 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to 30.8 months

Population: All Treated Population consisted of all participants who received at least one dose of GSK3326595 as monotherapy or at least one dose of both combination drugs as combination treatment.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=13 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=17 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: Percentage of Participants With Clinical Benefit Rate (CBR)	15 Percentage of Participants Interval 1.9 to 45.4	18 Percentage of Participants Interval 3.8 to 43.4

PRIMARY outcome

Timeframe: Up to 3 years and 2 months

Population: All Treated Population. Data was not collected as no participants were enrolled in Part 2.

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. Treatment emergent adverse event (TEAE) is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with non-STEAEs and STEAEs were planned to be assessed.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to 3 years and 2 months

Population: All Treated Population. Data was not collected as no participants were enrolled in Part 2.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to 28 days

Population: DLT Evaluable Population is defined as participants who received at least 75 percent (%) of the planned doses of GSK3326595 and all seven planned doses of 5-Azacitidine (Part 2) within the 28-day DLT observation period or those who have had a DLT. Data was not collected as no participants were enrolled in Part 2.

An event is considered to be a DLT if the event occurs within the first 28 days of treatment meeting one of the following criteria of toxicity, Hematologic: Grade 4 or greater treatment-emergent neutropenia, anemia, or thrombocytopenia, lasting for \>=14 days in the absence of Investigational Product, that cannot be attributed to underlying disease as described in National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4; Non-hematologic: Hepatic toxicity that meets Liver Stopping Criteria, Grade 3 nausea, vomiting or diarrhea that does not improve within 72 hours despite appropriate supportive treatments, Grade 4 or greater nausea, vomiting, or diarrhea of any duration, Any other Grade 3 or greater clinically significant non-hematologic toxicity; Other: Inability to receive all planned doses, dose interruption and Grade 2 or higher toxicity. Number of participants with DLTs were planned to be assessed.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to 3 years and 2 months

Population: All Treated Population. Data was not collected as no participants were enrolled in Part 2.

Number of participants with AEs leading to dose interruptions, dose reductions and treatment discontinuation due to AEs were planned to be assessed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 30.8 months

Population: All Treated Population

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. TEAEs which were not serious, were considered as non-STEAEs.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=13 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=17 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: Number of Participants With Common Non-STEAEs and STEAEs Common non-STEAEs	12 Participants	17 Participants
Part 1: Number of Participants With Common Non-STEAEs and STEAEs STEAEs	11 Participants	12 Participants

SECONDARY outcome

Timeframe: Up to 30.8 months

Population: All Treated Population

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Severity of each AE was reported during the study and was assigned a grade according to the NCI-CTCAE. AEs severity were graded as: Grade 1=mild; Grade 2=moderate; Grade 3=severe or medically significant but not immediately life-threatening; Grade 4=life-threatening consequences and Grade 5=death related to AE.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=13 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=17 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: Number of Participants With AEs by Severity Grade 2	1 Participants	0 Participants
Part 1: Number of Participants With AEs by Severity Grade 1	0 Participants	0 Participants
Part 1: Number of Participants With AEs by Severity Grade 3	0 Participants	6 Participants
Part 1: Number of Participants With AEs by Severity Grade 4	5 Participants	6 Participants
Part 1: Number of Participants With AEs by Severity Grade 5	7 Participants	5 Participants

SECONDARY outcome

Timeframe: Up to 28 days

Population: DLT Evaluable Population. Only those participants with data available at the indicated time points were analyzed.

An event is considered to be a DLT if the event occurs within the first 28 days of treatment meeting one of the following criteria of toxicity, Hematologic: Grade 4 or greater treatment-emergent neutropenia, anemia, or thrombocytopenia, lasting for \>=14 days in the absence of Investigational Product, that cannot be attributed to underlying disease as described in NCI-CTCAE version 4; Non-hematologic: Hepatic toxicity that meets Liver Stopping Criteria, Grade 3 nausea, vomiting or diarrhea that does not improve within 72 hours despite appropriate supportive treatments, Grade 4 or greater nausea, vomiting, or diarrhea of any duration, Any other Grade 3 or greater clinically significant non-hematologic toxicity; Other: Inability to receive all planned doses, dose interruption and Grade 2 or higher toxicity.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=10 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=16 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: Number of Participants With DLTs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 30.8 months

Population: All Treated Population.

Overall response rate is defined as the percentage of participants achieving a CR, mCR, or PR, per IWG criteria, where CR=Bone marrow: \<=5% myeloblasts with normal maturation of all cell lines; PR=Bone marrow blasts decreased by \>=50% over pre-treatment but still \>5%; mCR= Bone marrow: ≤ 5% myeloblasts and decrease by \>=50% over pre-treatment. Percentage values are rounded off.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=13 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=17 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: Overall Response Rate	0 Percentage of Participants Interval 0.0 to 24.7	6 Percentage of Participants Interval 0.1 to 28.7

SECONDARY outcome

Timeframe: Up to 30.8 months

Population: All Treated Population.

Progression free survival is defined as time from first dose to disease progression, as defined by IWG criteria, or death due to any cause, whichever occurs earlier. Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=13 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=17 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: Progression Free Survival	0.99 Months Interval 0.95 to 2.53	0.99 Months Interval 0.95 to 2.43

SECONDARY outcome

Timeframe: Up to 30.8 months

Population: All Treated Population.

Overall survival is defined as time from first dose to death due to any cause.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=13 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=17 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: Overall Survival	2.69 Months Interval 2.14 to 12.98	2.96 Months Interval 1.28 to 15.24

SECONDARY outcome

Timeframe: Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose

Population: Pharmacokinetic (PK) Population consisted of all participants from the All Treated Population for whom a PK sample was obtained and analyzed.

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=13 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=17 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK3326595 Following Administration of Single Dose	1322.8 Nanogram per milliliter Geometric Coefficient of Variation 50	960.4 Nanogram per milliliter Geometric Coefficient of Variation 61

SECONDARY outcome

Timeframe: Day 15:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose

Population: PK Population. Only those participants with data available at the indicated time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=10 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=17 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: Cmax of GSK3326595 Following Administration of Repeat Dose	1125.4 Nanogram per milliliter Geometric Coefficient of Variation 95	889.7 Nanogram per milliliter Geometric Coefficient of Variation 38

SECONDARY outcome

Population: PK Population

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=13 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=17 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: Time of Maximum Concentration Observed (Tmax) of GSK3326595 Following Administration of Single Dose	2.0000 Hours Interval 0.95 to 4.167	2.1667 Hours Interval 0.5 to 5.933

SECONDARY outcome

Population: PK Population. Only those participants with data available at the indicated time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=10 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=17 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: Tmax of GSK3326595 Following Administration of Repeat Dose	2.9833 Hours Interval 0.083 to 5.833	2.9500 Hours Interval 0.483 to 4.067

SECONDARY outcome

Population: PK Population. Only those participants with data available at the indicated time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=13 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=16 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK3326595 Following Administration of Single Dose	5.0755 Hours Geometric Coefficient of Variation 45.248	6.7688 Hours Geometric Coefficient of Variation 52.542

SECONDARY outcome

Population: PK Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=9 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=16 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: t1/2 of GSK3326595 Following Administration of Repeat Dose	6.2694 Hours Geometric Coefficient of Variation 47.757	6.8437 Hours Geometric Coefficient of Variation 67.132

SECONDARY outcome

Population: PK Population

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=13 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=17 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: Area Under Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within Participant Across All Treatments (AUC[0-t]) of GSK3326595 Following Administration of Single Dose	6667.4570 Hours*nanogram per milliliter Geometric Coefficient of Variation 56.989	5189.2734 Hours*nanogram per milliliter Geometric Coefficient of Variation 58.269

SECONDARY outcome

Population: PK Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=10 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=17 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: AUC(0-t) of GSK3326595 Following Administration of Repeat Dose	5750.5167 Hours*nanogram per milliliter Geometric Coefficient of Variation 211.317	5651.2792 Hours*nanogram per milliliter Geometric Coefficient of Variation 49.506

SECONDARY outcome

Population: PK Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=9 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=17 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: AUC From 0 Hours to the Time of Next Dosing (AUC[0-tau]) of GSK3326595	8460 Hours*nanogram per milliliter Geometric Coefficient of Variation 65.8	5830 Hours*nanogram per milliliter Geometric Coefficient of Variation 45.0

SECONDARY outcome

Population: PK Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=13 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=16 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of GSK3326595 Following Administration of Single Dose	7128.4358 Hours*nanogram per milliliter Geometric Coefficient of Variation 54.648	6572.8527 Hours*nanogram per milliliter Geometric Coefficient of Variation 52.385

SECONDARY outcome

Population: PK Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=9 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=16 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: AUC(0-inf) of GSK3326595 Following Administration of Repeat Dose	9202.5641 Hours*nanogram per milliliter Geometric Coefficient of Variation 70.085	6397.0840 Hours*nanogram per milliliter Geometric Coefficient of Variation 57.093

SECONDARY outcome

Population: PK Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=13 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=16 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: Oral Clearance (CL/F) of GSK3326595 Following Administration of Single Dose	56.1133 Liter per hour Geometric Coefficient of Variation 54.648	45.6423 Liter per hour Geometric Coefficient of Variation 52.385

SECONDARY outcome

Population: PK Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=9 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=17 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: CL/F of GSK3326595 Following Administration of Repeat Dose	47.2832 Liter per hour Geometric Coefficient of Variation 65.777	51.4710 Liter per hour Geometric Coefficient of Variation 45.010

SECONDARY outcome

Timeframe: Days1and15:Pre-dose(within 1hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hour(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour),24hours(+/-2hour)post-dose

Population: PK Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595. Time invariance was calculated as the ratio of AUC(0-24) on Day 15 divided by AUC(0-infinity) on Day 1 for GSK3326595.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=9 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=16 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: Time Invariance Following Administration of GSK3326595	1.3032 Ratio Geometric Coefficient of Variation 46.471	0.9485 Ratio Geometric Coefficient of Variation 57.938

SECONDARY outcome

Population: PK Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595. Accumulation ratio was calculated as the ratio of AUC(0-24) on Day 15 divided by AUC(0-24) on Day 1 for GSK3326595.

Outcome measures

Outcome measures
Measure	Part 1: GSK3326595 400 mg n=9 Participants Participants received GSK3326595 400 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.	Part 1: GSK3326595 300 mg n=16 Participants Participants received GSK3326595 300 mg, tablets, orally, once daily until progression, unacceptable toxicity, or withdrawal of consent during Part 1 of the study.
Part 1: Accumulation Ratio Following Administration of GSK3326595	1.3814 Ratio Geometric Coefficient of Variation 53.170	1.0774 Ratio Geometric Coefficient of Variation 41.113

SECONDARY outcome

Timeframe: Up to 3 years and 2 months

Population: All Treated Population. Data was not collected as no participants were enrolled in Part 2.

Complete remission rate is defined as percentage of participants achieving a CR per IWG criteria.