Trial Outcomes & Findings for First Time in Humans (FTIH) Study of GSK3368715 in Participants With Solid Tumors and Diffuse Large B-cell Lymphoma (DLBCL) (NCT NCT03666988)

Last Updated: 2022-05-20

Results Overview

A DLT is considered by the investigator to be clinically relevant,attributed event during the first 21days of intervention meeting the following criteria:Non-hematologic toxicity:Aspartate Aminotransferase(AST)/Alanine Aminotransferase(ALT) Grade 3/4,ALT\>=5 times Upper limit of Normal(ULN),ALT\>=3times ULN(\>=4 weeks),ALT\>=3 times ULN plus(+)bilirubin\>=2 times ULN,ALT \>= 3 times ULN+liver symptoms or International Normalization Ratio(INR)\>1.5.Nausea:Grade 3;Vomiting or diarrhea:Grade3/4(\>3days);Fatigue:Grade 3(\>5days).Hypertension:Uncontrolled Grade 3/4.Electrocardiogram(ECG)-change:\>20 milliseconds(msec) QRS extension.Lab abnormality:uncontrolled Grade3(\>3days)/Grade4.Hematologic toxicity:Neutropenia:uncontrolled Grade3(\>3days)/febrile neutropenia/Grade 4.Thrombocytopenia:uncontrolled Grade 3(\>3days)/Grade 3(clinically significant Hemorrhage)/Grade 4.Venous thromboembolism (VTE):Grade2 needing systemic anticoagulation/Grade\>=3 during the first 8 weeks or if sooner,study discontinuation

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

31 participants

Primary outcome timeframe

Up to 21 days

Results posted on

2022-05-20

Participant Flow

This was planned as a 2-part, first time in human study in participants with solid tumors and Diffuse Large B-Cell Lymphoma (DLBCL). Part 1 was planned to include dose escalation and food effect cohorts and Part 2 was an expansion cohort.

This study was terminated early during Part 1 as the benefit/risk assessment did not favor continuation of the study and therefore, Part 1: Food effect cohorts and Part 2 were not conducted. Total 31 participants were enrolled in Part 1 of the study.

Participant milestones

Participant milestones
Measure	Part 1 GSK3368715 50mg Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 50 milligrams (mg).	Part 1 GSK3368715 100mg Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 100mg.	Part 1 GSK3368715 200mg Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 200mg.
Part 1 (Up to 28 Months) STARTED	3	16	12
Part 1 (Up to 28 Months) COMPLETED	0	0	0
Part 1 (Up to 28 Months) NOT COMPLETED	3	16	12
Part 2 (Up to 48 Months) STARTED	0	0	0
Part 2 (Up to 48 Months) COMPLETED	0	0	0
Part 2 (Up to 48 Months) NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1 GSK3368715 50mg Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 50 milligrams (mg).	Part 1 GSK3368715 100mg Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 100mg.	Part 1 GSK3368715 200mg Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 200mg.
Part 1 (Up to 28 Months) Adverse Event	0	1	3
Part 1 (Up to 28 Months) Other	0	1	1
Part 1 (Up to 28 Months) Disease Progression	2	14	7
Part 1 (Up to 28 Months) Physician Decision	0	0	1
Part 1 (Up to 28 Months) Withdrawal by Subject	1	0	0

Baseline Characteristics

First Time in Humans (FTIH) Study of GSK3368715 in Participants With Solid Tumors and Diffuse Large B-cell Lymphoma (DLBCL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1 GSK3368715 50mg n=3 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 50 milligrams (mg).	Part 1 GSK3368715 100mg n=16 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 100mg.	Part 1 GSK3368715 200mg n=12 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 200mg.	Part 1:Food Effect Cohort: GSK3368715 Fasted Followed by Fed Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fasted state followed by fed state at or near the recommended Phase II dose (RP2D).	Part 1:Food Effect Cohort: GSK3368715 Fed Followed by Fasted Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fed state followed by fasted state at or near the RP2D.	Part 2 GSK3368715 Expansion Cohort Participants with DLBCL were planned to receive recommended Phase II dose (RP2D) based on Part 1 data.	Total n=31 Participants Total of all reporting groups
Age, Continuous	68.0 Years STANDARD_DEVIATION 6.56 • n=99 Participants	55.5 Years STANDARD_DEVIATION 15.12 • n=107 Participants	59.7 Years STANDARD_DEVIATION 10.89 • n=206 Participants	—	—	—	58.3 Years STANDARD_DEVIATION 13.23 • n=3 Participants
Sex: Female, Male Female	2 Participants n=99 Participants	4 Participants n=107 Participants	3 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	9 Participants n=3 Participants
Sex: Female, Male Male	1 Participants n=99 Participants	12 Participants n=107 Participants	9 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	22 Participants n=3 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	1 Participants n=3 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	2 Participants n=3 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	0 Participants n=99 Participants	2 Participants n=107 Participants	4 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	6 Participants n=3 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	3 Participants n=99 Participants	12 Participants n=107 Participants	6 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	21 Participants n=3 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	1 Participants n=3 Participants

PRIMARY outcome

Timeframe: Up to 21 days

Population: All-Treated Population included all participants who received at least one dose of GSK3368715. Data was not collected for Part 1: Food Effect Cohorts, as the study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts

Outcome measures

Outcome measures
Measure	Part 1 GSK3368715 50mg n=3 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 50 milligrams (mg).	Part 1 GSK3368715 100mg n=16 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 100mg.	Part 1 GSK3368715 200mg n=12 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 200mg.	Part 1: Food Effect Cohort: GSK3368715 Fasted Followed by Fed Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fasted state followed by fed state at or near the recommended Phase II dose (RP2D).	Part 1: Food Effect Cohort: GSK3368715 Fed Followed by Fasted Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fed state followed by fasted state at or near the RP2D.
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants	0 Participants	3 Participants	—	—

PRIMARY outcome

Timeframe: Up to 28 months

Population: All-Treated Population. Data was not collected for Part 1: Food Effect Cohorts, as the study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts

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. Any untoward event resulting in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE.

Outcome measures

Outcome measures
Measure	Part 1 GSK3368715 50mg n=3 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 50 milligrams (mg).	Part 1 GSK3368715 100mg n=16 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 100mg.	Part 1 GSK3368715 200mg n=12 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 200mg.	Part 1: Food Effect Cohort: GSK3368715 Fasted Followed by Fed Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fasted state followed by fed state at or near the recommended Phase II dose (RP2D).	Part 1: Food Effect Cohort: GSK3368715 Fed Followed by Fasted Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fed state followed by fasted state at or near the RP2D.
Part 1: Number of Participants With Non-Serious Adverse Events (Non-SAEs) and SAEs Any Non-SAE	3 Participants	15 Participants	9 Participants	—	—
Part 1: Number of Participants With Non-Serious Adverse Events (Non-SAEs) and SAEs Any SAE	2 Participants	4 Participants	6 Participants	—	—

PRIMARY outcome

Timeframe: Up to 28 months

All adverse events were analyzed using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. Graded from Grade 1: mild asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL), Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4: Life-threatening consequences; urgent intervention indicated, Grade 5: death related AE. Higher grade indicates more severe condition. Number of participants with maximum severity grades are presented.

Outcome measures

Outcome measures
Measure	Part 1 GSK3368715 50mg n=3 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 50 milligrams (mg).	Part 1 GSK3368715 100mg n=16 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 100mg.	Part 1 GSK3368715 200mg n=12 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 200mg.	Part 1: Food Effect Cohort: GSK3368715 Fasted Followed by Fed Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fasted state followed by fed state at or near the recommended Phase II dose (RP2D).	Part 1: Food Effect Cohort: GSK3368715 Fed Followed by Fasted Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fed state followed by fasted state at or near the RP2D.
Part 1: Number of Participants With AEs by Severity Grades Grade 1	1 Participants	0 Participants	2 Participants	—	—
Part 1: Number of Participants With AEs by Severity Grades Grade 2	1 Participants	9 Participants	1 Participants	—	—
Part 1: Number of Participants With AEs by Severity Grades Grade 3	1 Participants	5 Participants	5 Participants	—	—
Part 1: Number of Participants With AEs by Severity Grades Grade 4	0 Participants	1 Participants	2 Participants	—	—
Part 1: Number of Participants With AEs by Severity Grades Grade 5	0 Participants	0 Participants	2 Participants	—	—

PRIMARY outcome

Timeframe: Up to 48 months

Population: All-Treated Population. Data was not collected in Part 2 as the study was terminated early during Part 1 and hence no participant was enrolled in Part 2.

ORR is defined as the percentage of participants with a confirmed complete response (CR) or a partial response (PR). Participants with solid tumor were planned to be assessed per Response Criteria for Solid Tumors (RECIST) 1.1 and DLBCL participants were planned to be assessed per Lugano Criteria. This analysis was planned but not performed for Part 2 as the study was terminated during Part 1.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 28 months

Population: All Treated Population. Data was not collected for Part 1: Food Effect Cohorts, as the study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts

Overall response rate is defined as the percentage of participants with a confirmed complete response (CR) or a partial response (PR). Participants with solid tumor were assessed per Response Criteria for Solid Tumors (RECIST) 1.1 and DLBCL participants were assessed per Lugano Criteria. The best ORR was recorded from the start of the intervention until disease progression/recurrence and was determined based on the investigator's assessment of response at each time point. The percentage of participants achieving best overall response rate have been presented.

Outcome measures

Outcome measures
Measure	Part 1 GSK3368715 50mg n=3 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 50 milligrams (mg).	Part 1 GSK3368715 100mg n=16 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 100mg.	Part 1 GSK3368715 200mg n=12 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 200mg.	Part 1: Food Effect Cohort: GSK3368715 Fasted Followed by Fed Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fasted state followed by fed state at or near the recommended Phase II dose (RP2D).	Part 1: Food Effect Cohort: GSK3368715 Fed Followed by Fasted Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fed state followed by fasted state at or near the RP2D.
Part 1: Percentage of Participants Achieving Best Overall Response Rate	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	—	—

SECONDARY outcome

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2 ,3 ,4 ,6, 8, 12, 24, 48, 72 hours post-dose on Day 1; Pre-dose,30 minutes, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 15

Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). Data was not collected for Part 1: Food Effect Cohorts, as the study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts

Blood samples were collected at indicated time points. The pharmacokinetic (PK) parameters were calculated by non-compartmental analysis. PK Population included all participants in the All-Treated population from whom at least one PK sample was obtained, analyzed, and was measurable.

Outcome measures

Outcome measures
Measure	Part 1 GSK3368715 50mg n=3 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 50 milligrams (mg).	Part 1 GSK3368715 100mg n=16 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 100mg.	Part 1 GSK3368715 200mg n=12 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 200mg.	Part 1: Food Effect Cohort: GSK3368715 Fasted Followed by Fed Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fasted state followed by fed state at or near the recommended Phase II dose (RP2D).	Part 1: Food Effect Cohort: GSK3368715 Fed Followed by Fasted Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fed state followed by fasted state at or near the RP2D.
Part 1: Maximum Observed Plasma Concentration (Cmax) Following Administration of GSK3368715 GSK3368715 Day 1,n=3,16,12	107.166 Nanograms per milliliter Geometric Coefficient of Variation 48.81	197.420 Nanograms per milliliter Geometric Coefficient of Variation 112.05	336.771 Nanograms per milliliter Geometric Coefficient of Variation 72.57	—	—
Part 1: Maximum Observed Plasma Concentration (Cmax) Following Administration of GSK3368715 GSK3368715 Day 15,n=3,14,9	111.898 Nanograms per milliliter Geometric Coefficient of Variation 48.51	375.485 Nanograms per milliliter Geometric Coefficient of Variation 79.86	729.196 Nanograms per milliliter Geometric Coefficient of Variation 42.82	—	—

SECONDARY outcome

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose on Day 1; Pre-dose,30 minutes, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 15

Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).Data was not collected for Part 1: Food Effect Cohorts, as the study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Part 1 GSK3368715 50mg n=3 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 50 milligrams (mg).	Part 1 GSK3368715 100mg n=16 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 100mg.	Part 1 GSK3368715 200mg n=12 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 200mg.	Part 1: Food Effect Cohort: GSK3368715 Fasted Followed by Fed Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fasted state followed by fed state at or near the recommended Phase II dose (RP2D).	Part 1: Food Effect Cohort: GSK3368715 Fed Followed by Fasted Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fed state followed by fasted state at or near the RP2D.
Part 1: Time to Reach Cmax (Tmax) Following Administration of GSK3368715 GSK3368715 Day 1,n=3,16,12	0.5326 Hours Geometric Coefficient of Variation 180.404	0.6821 Hours Geometric Coefficient of Variation 94.273	1.1594 Hours Geometric Coefficient of Variation 86.483	—	—
Part 1: Time to Reach Cmax (Tmax) Following Administration of GSK3368715 GSK3368715 Day 15,n=3,14,9	1.7023 Hours Geometric Coefficient of Variation 132.169	0.8080 Hours Geometric Coefficient of Variation 44.215	0.9946 Hours Geometric Coefficient of Variation 66.296	—	—

SECONDARY outcome

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose on Day 1; Pre-dose,30 minutes, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 15

Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).Data was not collected for Part 1: Food Effect Cohorts, as the study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Part 1 GSK3368715 50mg n=3 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 50 milligrams (mg).	Part 1 GSK3368715 100mg n=16 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 100mg.	Part 1 GSK3368715 200mg n=12 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 200mg.	Part 1: Food Effect Cohort: GSK3368715 Fasted Followed by Fed Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fasted state followed by fed state at or near the recommended Phase II dose (RP2D).	Part 1: Food Effect Cohort: GSK3368715 Fed Followed by Fasted Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fed state followed by fasted state at or near the RP2D.
Part 1: Area Under the Concentration Time Curve From Time Zero to Last Time of Quantifiable Concentration (AUC [0-t]) Following Administration of GSK3368715 GSK3368715 Day 1,n=3,16,12	283.4828 Hour*nanogram per milliliter Geometric Coefficient of Variation 32.756	483.1405 Hour*nanogram per milliliter Geometric Coefficient of Variation 107.980	1400.0804 Hour*nanogram per milliliter Geometric Coefficient of Variation 64.718	—	—
Part 1: Area Under the Concentration Time Curve From Time Zero to Last Time of Quantifiable Concentration (AUC [0-t]) Following Administration of GSK3368715 GSK3368715 Day 15,n=3,14,9	437.2790 Hour*nanogram per milliliter Geometric Coefficient of Variation 91.371	1569.2088 Hour*nanogram per milliliter Geometric Coefficient of Variation 64.014	4870.1952 Hour*nanogram per milliliter Geometric Coefficient of Variation 45.623	—	—

SECONDARY outcome

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose on Day 1

Population: PK Population.Only those participants (par) with data available at specified data points were analyzed.Data not collected for Part (P)1:Food Effect Cohorts (FEC),as study was terminated early during P1;hence no par were enrolled in P1:FEC.AUC(0-infinity) could not be calculated for par in "P1 GSK3368715 50mg" arm,as atleast 3 data points are required in terminal elimination phase within same par;this criteria could not be fulfilled due to insufficient data above limit of quantification

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Part 1 GSK3368715 50mg Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 50 milligrams (mg).	Part 1 GSK3368715 100mg n=2 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 100mg.	Part 1 GSK3368715 200mg n=4 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 200mg.	Part 1: Food Effect Cohort: GSK3368715 Fasted Followed by Fed Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fasted state followed by fed state at or near the recommended Phase II dose (RP2D).	Part 1: Food Effect Cohort: GSK3368715 Fed Followed by Fasted Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fed state followed by fasted state at or near the RP2D.
Part 1: AUC From Time Zero Extrapolated to Infinite Time (AUC [0-infinity]) Following Administration of GSK3368715	—	1217.5147 Hour*nanogram per milliliter Geometric Coefficient of Variation 27.619	1674.8304 Hour*nanogram per milliliter Geometric Coefficient of Variation 50.515	—	—

SECONDARY outcome

Timeframe: Pre-dose, 30 minutes, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 15

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Part 1 GSK3368715 50mg n=2 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 50 milligrams (mg).	Part 1 GSK3368715 100mg n=14 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 100mg.	Part 1 GSK3368715 200mg n=9 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 200mg.	Part 1: Food Effect Cohort: GSK3368715 Fasted Followed by Fed Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fasted state followed by fed state at or near the recommended Phase II dose (RP2D).	Part 1: Food Effect Cohort: GSK3368715 Fed Followed by Fasted Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fed state followed by fasted state at or near the RP2D.
Part 1: Area Under the Concentration-time Curve From Time Zero to the Predose of the Next Dose [AUC (0-tau)] Following Administration of GSK3368715	581.9071 Hour*nanogram per milliliter Geometric Coefficient of Variation 101.434	1573.8450 Hour*nanogram per milliliter Geometric Coefficient of Variation 64.183	4861.3917 Hour*nanogram per milliliter Geometric Coefficient of Variation 45.288	—	—

SECONDARY outcome

Timeframe: Pre-dose on Day 1 and Day 15

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. Not applicable (NA) indicates that data could not be calculated as these were derivate values which were below the lower limit of quantification.

Outcome measures

Outcome measures
Measure	Part 1 GSK3368715 50mg n=3 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 50 milligrams (mg).	Part 1 GSK3368715 100mg n=16 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 100mg.	Part 1 GSK3368715 200mg n=11 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 200mg.	Part 1: Food Effect Cohort: GSK3368715 Fasted Followed by Fed Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fasted state followed by fed state at or near the recommended Phase II dose (RP2D).	Part 1: Food Effect Cohort: GSK3368715 Fed Followed by Fasted Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fed state followed by fasted state at or near the RP2D.
Part 1: Trough (Pre-dose) Concentration (Ctau) Following Administration of GSK3368715 GSK3368715 Day 1,n=3,16,11	5.150 Nanogram per milliliter Geometric Coefficient of Variation NA Data could not be calculated as these were derivate values which were below the lower limit of quantification.	7.880 Nanogram per milliliter Geometric Coefficient of Variation 18.46	12.642 Nanogram per milliliter Geometric Coefficient of Variation 73.85	—	—
Part 1: Trough (Pre-dose) Concentration (Ctau) Following Administration of GSK3368715 GSK3368715 Day 15,n=3,14,10	13.609 Nanogram per milliliter Geometric Coefficient of Variation 120.74	26.421 Nanogram per milliliter Geometric Coefficient of Variation 69.92	89.383 Nanogram per milliliter Geometric Coefficient of Variation 70.43	—	—

SECONDARY outcome

Timeframe: Pre-dose, 15, 30 minutes, 1 ,1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose on Day 1; Pre-dose, 30 minutes,1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 15

Population: PK Population. Only those participants with data available at the specified data points were analyzed. Data was not collected for Part 1: Food Effect Cohorts, as the study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts. Time invariance computation is dependent on AUC(0-infinity) and since AUC(0-infinity) could not be computed for participants in "Part 1 GSK3368715 50mg" arm, time invariance was not computable as well.

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. Time invariance was calculated as the ratio of AUC(0-24) on Day 15 / AUC (0-infinity) on Day 1 for GSK3368715.

Outcome measures

Outcome measures
Measure	Part 1 GSK3368715 50mg Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 50 milligrams (mg).	Part 1 GSK3368715 100mg n=2 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 100mg.	Part 1 GSK3368715 200mg n=4 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 200mg.	Part 1: Food Effect Cohort: GSK3368715 Fasted Followed by Fed Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fasted state followed by fed state at or near the recommended Phase II dose (RP2D).	Part 1: Food Effect Cohort: GSK3368715 Fed Followed by Fasted Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fed state followed by fasted state at or near the RP2D.
Part 1: Time Invariance Ratio Following Administration of GSK3368715	—	1.6007 Ratio Geometric Coefficient of Variation 15.614	2.9492 Ratio Geometric Coefficient of Variation 43.451	—	—

SECONDARY outcome

Timeframe: Pre-dose, 15, 30 minutes, 1 ,1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose on Day 1; Pre-dose, 30 minutes, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 15

Population: PK Population.Only those participants with data available at the specified data points were analyzed. Data was not collected for Part 1: Food Effect Cohorts,as study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts. Accumulation ratio could not be derived for "Part 1 GSK3368715 50mg" arm because there were no participant with AUC(0-24) values at both Day 1 and Day 15; hence, paired results were not available to calculate Accumulation ratio

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. Accumulation ratio (AR) was calculated as the ratio of AUC(0-24) on Day 15/Day 1 for GSK3368715.

Outcome measures

Outcome measures
Measure	Part 1 GSK3368715 50mg Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 50 milligrams (mg).	Part 1 GSK3368715 100mg n=7 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 100mg.	Part 1 GSK3368715 200mg n=9 Participants Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 200mg.	Part 1: Food Effect Cohort: GSK3368715 Fasted Followed by Fed Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fasted state followed by fed state at or near the recommended Phase II dose (RP2D).	Part 1: Food Effect Cohort: GSK3368715 Fed Followed by Fasted Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fed state followed by fasted state at or near the RP2D.
Part 1: Accumulation Ratio Following Administration of GSK3368715	—	2.6276 Ratio Geometric Coefficient of Variation 37.761	3.5953 Ratio Geometric Coefficient of Variation 40.900	—	—

SECONDARY outcome

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose on Day 1; Pre-dose, 1 and 4 hours post dose on Day 8, Pre-dose, 30 minutes, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 15

Population: PK Population. Data was not collected for Part 1: Food Effect Cohorts, as the study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts

Blood samples were planned to be collected at indicated time points in food effect cohorts (fasted followed by fed state and fed followed by fasted state). Samples were not collected due to early termination of study during Part 1; therefore, no analysis could be performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Blood samples were planned to be collected at indicated time points in food effect cohorts (fasted followed by fed state and fed followed by fasted state). Samples were not collected due to early termination of the study during Part 1; therefore, no analysis could be performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose on Day 1; Pre-dose, 1 and 4 hours post dose on Day 8, Pre-dose,30 minutes, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 15

Blood samples were planned to be collected at indicated time points in food effect cohorts (fasted followed by fed state and fed followed by fasted state). Samples were not collected due to early termination of the study during Part 1; therefore, no analysis could be performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose on Day 1; Pre-dose, 1 and 4 hours post dose on Day 8, Pre-dose,30 minutes,1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 15

Blood samples were planned to be collected at indicated time points in food effect cohorts (fasted followed by fed state and fed followed by fasted state). Samples were not collected due to early termination of the study during Part 1; therefore, no analysis could be performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Blood samples were planned to be collected at indicated time points in food effect cohorts (fasted followed by fed state and fed followed by fasted state). Samples were not collected due to early termination of the study during Part 1; therefore, no analysis could be performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 48 months

Population: All Treated Population. Data was not collected as the study was terminated early during Part 1 and hence no participants were enrolled in Part 2.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 48 months

Population: All Treated Population. Data was not collected as the study was terminated early during Part 1 and hence no participants were enrolled in Part 2.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 48 months

Population: All Treated Population. Data was not collected as the study was terminated early during Part 1 and hence no participants were enrolled in Part 2.

PFS is defined as the time from the first dose of study intervention to disease progression or death due to any cause, whichever occurs earlier. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5 ,2 ,3 ,4 ,6, 8, 12, 24, 48, 72 hours post-dose on Day 1; Pre-dose,30 minutes, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 15