Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

All Drugs and Chemicals

Antineoplastic Agents

Pharmaceutical Solutions

Antibodies

Antibodies, Monoclonal

Pembrolizumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants will receive GSK3174998 intravenously (IV) (dose range 0.003 to 10.0 milligram per kilogram \[mg/kg\]) every 3 weeks (Q3W) for up to 2 years or 35 cycles, whichever comes first.

Participants will receive GSK3174998 IV (dose range 0.003 to 10.0 mg/kg) Q3W for up to 2 years or 35 cycles, whichever comes first + Pembrolizumab 200 mg IV Q3W for up to 2 years or 35 cycles, whichever comes first.

Participants will receive GSK3174998 IV (at one dose level shown to be tolerable in dose escalation of part 2A) Q3W for up to 2 years or 35 cycles, whichever comes first + Pembrolizumab 200 mg IV Q3W for 2 years or 35 cycles, whichever comes first.

Lyophilized powder 40 mg reconstituted to get a dose range of 0.003 to \<=10 mg/kg to be given as IV infusion for 30 minutes (min), Q3W

GSK3174998

Pembrolizumab as 100 mg/4 milliliter (mL) solution (dose: 200 mg) to be given as IV infusion for 30 min, Q3W

GSK Clinical Trials

This is a first time in human (FTIH), open-label, non-randomized, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary clinical activity of GSK3174998 administered intravenously to participants with selected advanced or recurrent solid tumors. This dose-escalation study will assess the safety, activity of GSK3174998 as monotherapy (Part 1), in combination with pembrolizumab (Part 2), and potentially in combination with additional therapies.

The study will be conducted in 2 parts, each part consisting of starting with a dose-escalation phase followed by a cohort expansion phase. GSK3174998 will first be evaluated as monotherapy in escalating doses. Once a dose of GSK3174998 has been identified that is both tolerable and demonstrates pharmacodynamic activity, enrollment of Part 2 may begin. In Part 2, escalating doses of GSK3174998 will be evaluated with fixed doses of pembrolizumab.

The maximum duration of treatment with GSK3174998 and pembrolizumab will be approximately 2 years or 35 cycles, whichever comes first. The follow-up period for safety assessments will be a minimum of 3 months from the date of the last dose. The post-treatment follow-up period will include disease assessments every 12 weeks until documented progressive disease (PD). Approximately 141 participants with selected advanced or recurrent solid tumors will be enrolled.

GSK3174998 Alone and With Pembrolizumab in Participants With Advanced Solid Tumors (ENGAGE-1)

A Phase I, Open-Label Study of GSK3174998 Administered Alone and in Combination With Anticancer Agents Including Pembrolizumab in Subjects With Selected Advanced Solid Tumors

IPD for this study will be made available via the Clinical Study Data Request site.

An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE.

An adverse event was considered as DLT if it was considered by the investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment, occurred within the first 28 days of the treatment, and met 1 of the following criteria: Hematologic: Febrile neutropenia, Grade4 neutropenia of \>7days requiring Granulocyte colony-stimulating factor (G-CSF), Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding as described in National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of \>=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT.

An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any adverse event leading to withdrawal from the study is presented.

Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented.

Blood samples were collected for the analysis of following hematology parameters: hemoglobin (Hb), leukocyte count (leuko.), lymphocyte count (Lymph.), neutrophil count (Neutro.) and platelet count (PC). The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.

Blood samples were collected for the analysis of following hematology parameters: Hb, leuko., Lymph., Neutro. and PC. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.

Blood samples were collected for the analysis of following liver function laboratory parameters: alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.

Blood samples were collected for the analysis of following liver function laboratory parameters: ALT, ALP, AST and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.

SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: \<120 millimeter mercury (mmHg); Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: \>=160 mmHg. For DBP: Grade 0: \<80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: \>=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.

SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: \<120 mmHg; Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: \>=160 mmHg. For DBP: Grade 0: \<80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: \>=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.

Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: \<60 beats per minute \[bpm\]', normal HR: 60 to 100 bpm and high HR: \>100 bpm. If values were unchanged (example: increase to \>100 bpm to increase to \>100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.

Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: \<60 bpm', normal HR: 60 to 100 bpm and high HR: \>100 bpm. If values were unchanged (example: increase to \>100 bpm to increase to \>100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.

Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: \<=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: \>=38 degrees Celsius. If values were unchanged (example: increase to \>=38 degrees Celsius to increase to \>=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.

A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented.

ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or a partial response (PR) as the Best Overall Response (BOR), as assessed by the investigator per Response Evaluation Criteria In Solid Tumors (RECIST) Version (v) 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter. PR: \>=30 percent (%) decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart.

ORR is defined as the percentage of participants achieving a confirmed CR or PR as the BOR, as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter. PR: \>=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart.

DCR is defined as the percentage of participants with a confirmed CR or PR at any time, plus stable disease (SD) \>=12 weeks as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter. PR: \>=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. SD: 30% decrease in tumor burden compared with Baseline cannot be established nor 20% increase compared with nadir.

DCR is defined as the percentage of participants with a confirmed CR or PR at any time, plus SD \>=12 weeks as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter. PR: \>=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. SD: 30% decrease in tumor burden compared with Baseline cannot be established nor 20% increase compared with nadir.

Blood samples for pharmacokinetic (PK) analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion (EOI); anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion.

Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion (EOI); anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion.

Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.

Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.

Blood samples for PK analysis of pembrolizumab were collected on Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion (EOPI); anytime on Days 8,15; Pre-dose on Days 22, 64, 106.

Blood samples for PK analysis of pembrolizumab were collected on Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15; Pre-dose on Days 22, 64, 106.

Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.

Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.

Serum samples were collected for the determination of anti-GSK3174998 antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a GSK3174998 bridging style ADA assay with a bio-analytically determined cut-point determined during assay validation. Samples taken after dosing with GSK3174998 that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-GSK3174998 antibodies results at any visit during the study have been presented.

Serum samples were collected for the determination of anti-GSK3174998 antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a GSK3174998 bridging style ADA assay with a bio-analytically determined cut-point (determined during assay validation). Samples taken after dosing with GSK3174998 that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-GSK3174998 antibodies results at any visit during the study have been presented.

Serum samples were collected for the determination of anti-pembrolizumab antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a pembrolizumab bridging style ADA assay with a bio-analytically determined cut-point (determined during assay validation). Samples taken after dosing with pembrolizumab that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-pembrolizumab antibodies results at any visit during the study have been presented.

Serum samples were planned to be collected for the determination of anti-pembrolizumab antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps.

Merck Sharp & Dohme LLC

GlaxoSmithKline

All-cause mortality, SAEs and non-SAEs were collected for All Treated Population which comprised of all participants who received at least one dose of GSK3174998.

Participants received intravenous (IV) dose of GSK3174998 0.003 milligram per kilogram (mg/kg) every 3 weeks (wks) in Part 1.

Part 1: GSK3174998 0.003 mg/kg

Participants received IV dose of GSK3174998 0.01 mg/kg every 3 weeks (Q3W) in Part 1.

Part 1: GSK3174998 0.01 mg/kg

Participants received IV dose of GSK3174998 0.03 mg/kg Q3W in Part 1.

Part 1: GSK3174998 0.03 mg/kg

Participants received IV dose of GSK3174998 0.1 mg/kg Q3W in Part 1.

Part 1: GSK3174998 0.1 mg/kg

Participants received IV dose of GSK3174998 0.3 mg/kg Q3W in Part 1.

Part 1: GSK3174998 0.3 mg/kg

Participants received IV dose of GSK3174998 1.0 mg/kg Q3W in Part 1.

Part 1: GSK3174998 1.0 mg/kg

Participants received IV dose of GSK3174998 3.0 mg/kg Q3W in Part 1.

Part 1: GSK3174998 3.0 mg/kg

Participants received IV dose of GSK3174998 10.0 mg/kg Q3W in Part 1.

Part 1: GSK3174998 10.0 mg/kg

Participants received IV dose of GSK3174998 0.003 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A.

Part 2A: GSK3174998 0.003 mg/kg + Pembrolizumab 200 mg

Participants received IV dose of GSK3174998 0.01 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A.

Part 2A: GSK3174998 0.01 mg/kg + Pembrolizumab 200 mg

Participants received IV dose of GSK3174998 0.03 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A.

Part 2A: GSK3174998 0.03 mg/kg + Pembrolizumab 200 mg

Participants received IV dose of GSK3174998 0.1 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A.

Part 2A: GSK3174998 0.1 mg/kg + Pembrolizumab 200 mg

Participants received IV dose of GSK3174998 0.3 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A.

Part 2A: GSK3174998 0.3 mg/kg + Pembrolizumab 200 mg

Participants received IV dose of GSK3174998 1.0 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A.

Part 2A: GSK3174998 1.0 mg/kg + Pembrolizumab 200 mg

Participants received IV dose of GSK3174998 3.0 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A.

Part 2A: GSK3174998 3.0 mg/kg + Pembrolizumab 200 mg

Participants received IV dose of GSK3174998 10.0 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A.

Part 2A: GSK3174998 10.0 mg/kg + Pembrolizumab 200 mg

Participants with melanoma were included in this cohort and received IV dose of GSK3174998 0.3 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2B.

Part 2B: Melanoma Cohort

Participants with soft tissue sarcoma were included in this cohort and received IV dose of GSK3174998 0.3 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2B.

Part 2B: Soft Tissue Sarcoma Cohort

Participants with non-small cell lung cancer (NSCLC) were included in this cohort and received IV dose of GSK3174998 0.3 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2B.

Part 2B: NSCLC Cohort

Total

Age, Customized

Sex: Female, Male

Race

Race/Ethnicity, Customized

GSK Response Center

Any SAE

Any non-SAE

All Treated Population consisted of all participants who received at least one dose of GSK3174998.

Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE)

Part 2A: Number of Participants With Any SAE and Non-SAE

Part 2B: Number of Participants With Any SAE and Non-SAE

Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)

Part 2A: Number of Participants With DLTs

Part 2B: Number of Participants With DLTs

Part 1: Number of Participants With Any Adverse Event Leading to Withdrawal (AELD) From the Study

Part 2A: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study

Part 2B: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study

Dose reduction

Dose delay

Part 1: Number of Participants With Dose Reductions or Delay

Part 2A: Number of Participants With Dose Reductions or Delay

Part 2B: Number of Participants With Dose Reductions or Delay

Hb decreased (anemia)

Hb increased

Leuko. increased

Leuko. decreased

Lymph. decreased

Lymph. increased

Neutro. decreased

PC decreased

Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters

Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters

Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters

ALT increased

ALP increased

AST increased

Bilirubin increased

Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters

Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters

Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters

Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP

Part 2B: Number of Participants With Any Grade Change From Baseline in SBP and DBP

Decrease to low

Change to normal or no change

Increase to high

Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR)

Part 2A: Number of Participants With Worst Case Change From Baseline in HR

Part 2B: Number of Participants With Worst Case Change From Baseline in HR

Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature

Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature

Part 2B: Number of Participants With Worst Case Change From Baseline in Body Temperature

Part 1: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant Electrocardiogram (ECG) Findings

All Treated Population. Only those participants with data available at the indicated data points were analyzed.

Part 2A: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings

Part 2B: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings

Part 1: Objective Response Rate (ORR)

All Treated Population. The efficacy outputs were presented according to planned study treatment. One participant in Part 2A was planned for 0.01mg, but received 0.003mg at first dose in error. One participant in Part 2A was planned for 0.003mg, but received 0.3mg at first dose in error. Hence, 'N' for the 'Part 2A: GSK3174998 0.01 mg/kg+Pembrolizumab 200 mg' arm is greater than that for the Participant Flow.

Part 2A: Objective Response Rate (ORR)

Part 2B: Objective Response Rate (ORR)

Part 1: Disease Control Rate (DCR)

Part 2A: Disease Control Rate (DCR)

Part 2B: Disease Control Rate (DCR)

Day 1, predose, n=1,1,8,10,10,4,7,4

Day1, 30minutes after EOI, n=1,1,8,10,10,4,7,4

Day1, 4hour after EOI, n=1,1,8,10,9,4,7,4

Day1, 24hour after EOI, n=1,1,6,10,9,4,7,4

Day 8, n=1,1,8,10,10,3,7,4

Day 14, n=1,1,8,9,10,3,7,4

Day 22, predose, n=1,1,8,10,10,4,7,4

Day22, 30minutes after EOI, n=1,1,8,10,10,4,7,4

Day22, 4hour after EOI, n=1,1,8,10,9,4,7,4

Day22, 24hour after EOI, n=1,0,6,9,9,4,7,4

Day 29, n=0,1,8,10,10,4,7,4

Day 36, n=0,1,7,9,9,4,6,4

Day 43, predose, n=0,1,6,8,9,4,5,3

Day43, 30minutes after EOI, n=0,1,6,7,9,3,5,3

Day 64, predose, n=0,1,5,5,7,4,4,3

Day64, 30minutes after EOI, n=0,0,5,5,7,4,4,2

Day 85, predose, n=0,0,1,4,3,2,2,3

Day85, 30minutes after EOI, n=0,0,1,4,3,2,2,3

Day106, predose, n=0,0,1,1,2,2,1,2

Day106, 30minutes after EOI, n=0,0,0,1,3,2,1,2

Pharmacokinetic Population consisted of all participants from the All Treated Population for whom a PK sample was obtained and analyzed. Only those participants with data available at the indicated data points were analyzed (represented by n=X in category titles).

Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points

Day 1, predose, n=4,5,9,10,11,11,12,4

Day1, 30minutes after EOI, n=4,5,9,10,11,11,12,4

Day1, 4hour after EOI, n=4,5,9,10,11,11,12,4

Day1, 24hour after EOI, n=4,5,9,10,11,11,12,4

Day 8, n=4,5,10,11,14,11,12,4

Day 15, n=4,4,10,10,12,11,12,4

Day 22, predose, n=3,2,10,10,12,10,12,3

Day22, 30minutes after EOI, n=3,2,10,10,12,9,12,3

Day22, 4hour after EOI, n=3,2,9,10,12,9,12,3

Day22, 24hour after EOI, n=3,2,7,7,9,10,12,3

Day 29, n=3,1,9,10,10,10,12,1

Day 36, n=3,2,8,8,8,10,11,1

Day 43, predose, n=3,3,7,7,8,9,12,1

Day43, 30minutes after EOI, n=3,3,7,7,8,8,12,1

Day 64, predose, n=1,3,2,6,4,8,10,0

Day64, 30minutes after EOI, n=1,3,2,7,4,8,10,0

Day 85, predose, n=0,3,0,5,5,7,8,0

Day85, 30minutes after EOI, n=0,3,0,5,5,7,8,0

Day106, predose, n=0,1,0,5,5,5,8,0

Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed (represented by n=X in category titles).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
GSK3174998 Alone and With Pembrolizumab in Participants With Advanced Solid Tumors (ENGAGE-1)	NCT02528357	Neoplasms	GSK3174998 Pembrolizumab	18 Years -	GlaxoSmithKline
Study of IMC-1121B (Ramucirumab) With Best Supportive Care in Participants With Gastric Cancer and Adenocarcinoma	NCT00917384	Gastric Cancer Adenocarcinoma	ramucirumab Placebo Best Supportive...	18 Years -	Eli Lilly and Company
Study of IMC-11F8 in Participants With Advanced Solid Tumors	NCT01088464	Neoplasms	IMC-11F8 IMC-11F8 IMC-11F8	20 Years -	Eli Lilly and Company
Study of IMC-11F8 in Participants With Advanced Solid Tumors	NCT01088464	Neoplasms	IMC-11F8 IMC-11F8 IMC-11F8	20 Years -	Eli Lilly and Company
Study of a PD-1 Inhibitor (JTX-4014) in Subjects With Solid Tumor Malignancies	NCT03790488	Cancer	JTX-4014	18 Years -	Jounce Therapeutics, Inc.

Spots Global Cancer Trial Database for monoclonal antibody (mab)