Completed
PHASE1
INTERVENTIONAL
NCT03447314
Study of a Combination of GSK1795091 and Immunotherapies in Subjects With Advanced Solid Tumors
View on ClinicalTrials.gov
Updated Dec 15, 2025
Brief Summary
GSK1795091 is being developed for administration in combination with other immune system modulators for the treatment of cancers. The study will be conducted in two parts. In Part 1, dose escalation will be performed to identify combination dose levels comprising GSK1795091 with either 24 milligrams (mg) GSK3174998 (Part 1a), 80 mg GSK3359609 (Part 1b), or 200 mg pembrolizumab (Part 1c). One dose level of GSK3174998, GSK3359609, or pembrolizumab with up to 5 dose levels of GSK1795091 are planned for evaluation. In Part 2 (dose-expansion), subjects will receive a single dose level of GSK1795091 as identified based on data from Part 1, in combination with either GSK3174998, GSK3359609, or pembrolizumab.
Interventions
Name:
GSK1795091
Type:
DRUG
Description:
GSK1795091 will be available as solution for injection
Name:
GSK3174998
Type:
DRUG
Description:
GSK3174998 will be available as lyophilized powder to be reconstituted for infusion.
Name:
GSK3359609
Type:
DRUG
Description:
GSK3359609 will be available as solution for infusion.
Name:
Pembrolizumab
Type:
DRUG
Description:
Pembrolizumab will be available as solution for infusion or lyophilized powder for reconstitution.
Primary Outcomes
Measure:
Part 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs (STEAEs)
TimeFrame:
Up to 27 months
Description:
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A serious adverse event 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 or associated with liver injury and impaired liver function. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication. All Treated Population consisted of all participants who received at least 1 dose of GSK1795091, GSK3174998, GSK3359609, or pembrolizumab.
Measure:
Part 2: Number of Participants With TEAEs and STEAEs
TimeFrame:
Up to 27 months
Description:
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A serious adverse event 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 or associated with liver injury and impaired liver function. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
Measure:
Part 1: Number of Participants With Dose-limiting Toxicity (DLT)
TimeFrame:
42 days
Description:
An adverse event was considered to be a DLT if it was considered by investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment and met one of the criteria: hematologic toxicity-Grade4 neutropenia of \>7 days duration or febrile neutropenia, Grade 4 anemia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding as described in Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, non-hematologic toxicity-Grade 4 toxicity, Grade 3 toxicity that does not resolve to \<=Grade 1 or Baseline within 14 days despite optimal supportive care, alanine aminotransferase (ALT) \>=5 times upper limit of normal (ULN), ALT \>=3 times ULN persists for \>=4 weeks, ALT \>=3 times ULN and bilirubin \>=2 times ULN (\>35 percent \[%\] direct bilirubin), ALT \>=3 times ULN and international normalized ratio (INR) \>1.5, ALT \>=3 times ULN associated with symptoms (new or worsening) believed to be related to liver injury or hypersensitivity.
Measure:
Part 1: Number of Participants With TEAEs Leading to Discontinuation
TimeFrame:
Up to 2 years
Description:
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
Measure:
Part 2: Number of Participants With TEAEs Leading to Discontinuation
TimeFrame:
Up to 2 years
Description:
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
Measure:
Part 1: Number of Participants With TEAEs Leading to Dose Reductions or Dose Delays
TimeFrame:
Up to 2 years
Description:
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
Measure:
Part 2: Number of Participants With TEAEs Leading to Dose Reductions or Dose Delays
TimeFrame:
Up to 2 years
Description:
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
Measure:
Part 1: Number of Participants With Change From Baseline in Hematology Parameters With Respect to the Normal Range
TimeFrame:
Baseline (Day 1: Pre-dose) and up to 2 years
Description:
Blood samples were collected for the analysis of following hematology parameters: neutrophils (Neutro), lymphocytes (lympho), monocytes (Mono), eosinophils (Eosino), basophils (Baso), hemoglobin (Hb), hematocrit (Hct), erythrocytes (Erythro), erythrocyte mean corpuscular volume (EMCV), erythrocyte mean corpuscular hemoglobin (EMCH) and platelet count (PC). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data was categorized as decrease to low (D to L) (value below lower limit of normal range \[LNR\]) and increase to high (I to H) (value above upper LNR). Participants were counted twice if participant had both decreased to low and increased to high within an assessment. Data for worst-case on therapy for categories decrease to low and increase to high is presented.
Measure:
Part 2: Number of Participants With Change From Baseline in Hematology Parameters With Respect to the Normal Range
TimeFrame:
Baseline (Day 1: Pre-dose) and up to 2 years
Description:
Blood samples were planned to be collected for the analysis of following hematology parameters: neutrophils, lymphocytes, monocytes, eosinophils, basophils, hemoglobin, hematocrit, erythrocytes, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin and platelet count.
Measure:
Part 1: Number of Participants With Change From Baseline in Chemistry Parameters With Respect to the Normal Range
TimeFrame:
Baseline (Day 1: Pre-dose) and up to 2 years
Description:
Blood samples were collected for the analysis of following chemistry parameters: urea, creatinine (Cr), glucose (Glu), potassium (Pot), sodium (Sod), calcium (Cal), aspartate aminotransferase (AST), ALT, alkaline phosphatase (ALP), bilirubin (Bil), direct bilirubin (D.Bil), protein, albumin (Alb), C-reactive protein (CRP) and Creatinine Clearance (CrCl). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data was categorized as decrease to low (value below the lower LNR), and increase to high (value above the upper LNR). Participants were counted twice if the participant had both decreased to low and increased to high within an assessment. Data for worst case on therapy for categories decrease to low and increase to high is presented.
Measure:
Part 2: Number of Participants With Change From Baseline in Chemistry Parameters With Respect to the Normal Range
TimeFrame:
Baseline (Day 1: Pre-dose) and up to 2 years
Description:
Blood samples were planned to be collected for the analysis of following chemistry parameters: urea, creatinine, glucose, potassium, sodium, calcium, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, direct bilirubin, protein, albumin, C-reactive protein and Creatinine Clearance.
Measure:
Part 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria
TimeFrame:
Up to 2 years
Description:
Urine samples were collected for the analysis of following urinalysis parameters: glucose (Glu), protein (Pro), occult blood (OB), ketones, potential of hydrogen (pH) and specific gravity (SpGr) by dipstick method. The dipstick test gives results in a semi-quantitative manner. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The reference range is 1.002-1.030. Urine pH is an acid-base measurement. Normal urine has a slightly acid pH (5.0 - 6.0). Data was categorized as decrease to low (value below the lower LNR) and increase to high (value above the upper LNR). Participants were counted twice if the participant had both decreased to low and increased to high within an assessment. Data for worst-case on therapy for categories decrease to low and increase to high is presented.
Measure:
Part 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria
TimeFrame:
Up to 2 years
Description:
Urine samples were planned to be collected for the analysis of following urine parameters: glucose, protein, occult blood, ketones, potential of hydrogen and specific gravity by dipstick method.
Measure:
Part 1: Number of Participants With Increase From Baseline in Vital Signs According to Markedly Abnormal Criteria
TimeFrame:
Up to 2 years
Description:
Vital signs including systolic blood pressure (SBP), diastolic BP (DBP), pulse rate (PR) and body temperature (BT) were measured in a semi-supine position after 5 minutes rest for the participants. SBP: Category1 (\>140 and \<161 millimeter of mercury\[mmHg\]), Category 2 (\>=161 and \<181 mmHg), Category3 (\>=181 mmHg); DBP: Category1 (\>90 and \<101 mmHg), Category 2 (\>=101 and \<111 mmHg), Category 3 (\>=111 mmHg); PR: Category 1 (\>101 and \<116 beats per minutes\[bpm\]), Category 2 (\>=116 and \<131 bpm), Category 3 (\>=131 bpm); BT: Category 1 (\>38.0 and \<38.6 degrees Celsius), Category 2 (\>=38.6 and \<39.1 degrees Celsius), Category 3 (\>=39.1 degrees Celsius). Data for any increase in category at worst case on therapy is presented.
Measure:
Part 2: Number of Participants With Vital Signs Any Increases From Baseline According to Markedly Abnormal Criteria
TimeFrame:
Up to 2 years
Description:
Vital signs including SBP, DBP, pulse rate and body temperature were planned to be measured in a semi-supine position after 5 minutes rest for the participants.
Measure:
Part 1: Number of Participants With Any Decrease From Baseline in Vital Sign According to Markedly Abnormal Criteria
TimeFrame:
Up to 2 years
Description:
Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest for the participants. For SBP: a decrease in Category was defined as \<80 mmHg decrease from Baseline; DBP: decrease defined as Category (\<50 mmHg decrease from Baseline); pulse rate: decrease defined as Category (\<45 bpm decrease from Baseline). Data for decrease in category at worst case on therapy is presented.
Measure:
Part 2: Number of Participants With Vital Signs Any Decreases From Baseline According to Markedly Abnormal Criteria
TimeFrame:
Up to 2 years
Description:
Vital signs including SBP, DBP and pulse rate were planned to be measured in a semi-supine position after 5 minutes rest for the participants.
Measure:
Part 1: Number of Participants With Any Increase From Baseline in Corrected QT Interval Using Fredericia's Formula (QTcF) According to Markedly Abnormal Criteria
TimeFrame:
Up to 2 years
Description:
12-lead electrocardiogram (ECG) was obtained at indicated time point using an automated ECG machine that measured QTcF interval. QTc parameters were graded according to National Cancer Institute - CTCAE version 4.0. Grade 1 (\>450 milliseconds \[msec\]), Grade 2 (\>480 msec), Grade 3 (\>500 msec). An increase is defined as an increase in CTCAE grade relative to Baseline grade. Data for any grade increase at worst case on therapy is presented.
Measure:
Part 2: Number of Participants With Any QTcF Interval Increases From Baseline According to Markedly Abnormal Criteria
TimeFrame:
Up to 2 years
Description:
12-lead ECG was planned to be performed to measure QTcF interval.
Trial Information
NCT ID
NCT03447314
Status
Completed
Study Type
INTERVENTIONAL
Phases
PHASE1
Sponsor
GlaxoSmithKline
Last Updated
December 15, 2025