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Study of a Combination of GSK1795091 and Immunotherapies in Subjects With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03447314
Recruitment Status : Active, not recruiting
First Posted : February 27, 2018
Results First Posted : July 20, 2021
Last Update Posted : July 20, 2021
Sponsor:
Collaborator:
Iqvia Pty Ltd
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE February 21, 2018
First Posted Date  ICMJE February 27, 2018
Results First Submitted Date  ICMJE June 15, 2021
Results First Posted Date  ICMJE July 20, 2021
Last Update Posted Date July 20, 2021
Actual Study Start Date  ICMJE March 26, 2018
Actual Primary Completion Date July 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 16, 2021)
  • Part 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs (STEAEs) [ Time Frame: Up to 27 months ]
    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.
  • Part 2: Number of Participants With TEAEs and STEAEs [ Time Frame: Up to 27 months ]
    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.
  • Part 1: Number of Participants With Dose-limiting Toxicity (DLT) [ Time Frame: 42 days ]
    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.
  • Part 1: Number of Participants With TEAEs Leading to Discontinuation [ Time Frame: Up to 2 years ]
    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.
  • Part 2: Number of Participants With TEAEs Leading to Discontinuation [ Time Frame: Up to 2 years ]
    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.
  • Part 1: Number of Participants With TEAEs Leading to Dose Reductions or Dose Delays [ Time Frame: Up to 2 years ]
    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.
  • Part 2: Number of Participants With TEAEs Leading to Dose Reductions or Dose Delays [ Time Frame: Up to 2 years ]
    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.
  • Part 1: Number of Participants With Change From Baseline in Hematology Parameters With Respect to the Normal Range [ Time Frame: Baseline (Day 1: Pre-dose) and up to 2 years ]
    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.
  • Part 2: Number of Participants With Change From Baseline in Hematology Parameters With Respect to the Normal Range [ Time Frame: Baseline (Day 1: Pre-dose) and up to 2 years ]
    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.
  • Part 1: Number of Participants With Change From Baseline in Chemistry Parameters With Respect to the Normal Range [ Time Frame: Baseline (Day 1: Pre-dose) and up to 2 years ]
    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.
  • Part 2: Number of Participants With Change From Baseline in Chemistry Parameters With Respect to the Normal Range [ Time Frame: Baseline (Day 1: Pre-dose) and up to 2 years ]
    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.
  • Part 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria [ Time Frame: Up to 2 years ]
    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.
  • Part 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria [ Time Frame: Up to 2 years ]
    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.
  • Part 1: Number of Participants With Increase From Baseline in Vital Signs According to Markedly Abnormal Criteria [ Time Frame: Up to 2 years ]
    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.
  • Part 2: Number of Participants With Vital Signs Any Increases From Baseline According to Markedly Abnormal Criteria [ Time Frame: Up to 2 years ]
    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.
  • Part 1: Number of Participants With Any Decrease From Baseline in Vital Sign According to Markedly Abnormal Criteria [ Time Frame: Up to 2 years ]
    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.
  • Part 2: Number of Participants With Vital Signs Any Decreases From Baseline According to Markedly Abnormal Criteria [ Time Frame: Up to 2 years ]
    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.
  • Part 1: Number of Participants With Any Increase From Baseline in Corrected QT Interval Using Fredericia's Formula (QTcF) According to Markedly Abnormal Criteria [ Time Frame: Up to 2 years ]
    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.
  • Part 2: Number of Participants With Any QTcF Interval Increases From Baseline According to Markedly Abnormal Criteria [ Time Frame: Up to 2 years ]
    12-lead ECG was planned to be performed to measure QTcF interval.
Original Primary Outcome Measures  ICMJE
 (submitted: February 21, 2018)
  • Number of subjects with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 2 years ]
    AEs will be assessed at each visit from first dose until the treatment discontinuation visit (TDV) and until 90 days after last dose for adverse events of special interest (AESI) and SAEs.
  • Number of subjects with dose-limiting toxicities (DLTs) [ Time Frame: Start of treatment to 6 weeks ]
    An AE is considered to be a DLT if it is considered by the investigator to be clinically relevant and is attributed to the study treatment and meets at least 1 of the pre-specified criteria.
  • Number of subjects withdrawn due to AEs [ Time Frame: Up to 2 years ]
    The number of subjects withdrawn due to AEs throughout the study will be summarized.
  • Number of subjects with dose reductions or delays [ Time Frame: Up to 2 years ]
    The number of subjects with dose reductions or delays will be summarized.
  • Number of subjects with abnormal hematology parameters [ Time Frame: Up to 2 years ]
    The following hematology parameters will be evaluated: platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), neutrophils, lymphocytes, monocytes, eosinophils and basophils.
  • Number of subjects with abnormal clinical chemistry parameters [ Time Frame: Up to 2 years ]
    The following clinical chemistry parameters will be evaluated: blood urea nitrogen (BUN), creatinine, glucose, calculated creatinine clearance (CrCl), potassium, sodium, calcium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, C-reactive protein, total and direct bilirubin, total protein and albumin.
  • Number of subjects with abnormal urine parameters [ Time Frame: Up to 2 years ]
    The following parameters will be evaluated in urine: specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick method. Microscopic examination will be performed if blood or protein is abnormal.
  • Number of subjects with abnormal temperature [ Time Frame: Up to 2 years ]
    Temperature will be measured in semi-supine position after 5 minutes of rest.
  • Number of subjects with abnormal blood pressure [ Time Frame: Up to 2 years ]
    Systolic and diastolic blood pressure will be measured in semi-supine position after 5 minutes of rest.
  • Number of subjects with abnormal pulse rate [ Time Frame: Up to 2 years ]
    Pulse rate will be measured in semi-supine position after 5 minutes of rest.
  • Number of subjects with abnormal electrocardiogram (ECG) measurement [ Time Frame: Up to 2 years ]
    Twelve-lead ECGs will be obtained using an ECG machine after at least 10 minutes of rest.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2021)
  • Part 1: Objective Response Rate [ Time Frame: Up to 2 years ]
    Objective response rate is defined as the percentage of participants achieving a confirmed best overall response of complete response (CR) or partial response (PR) evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1, where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeters (mm) in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
  • Part 2: Objective Response Rate [ Time Frame: Up to 2 years ]
    Objective response rate is defined as the percentage of participants achieving a confirmed best overall response of CR or PR evaluated using RECIST v 1.1, where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
  • Part 1: Disease Control Rate [ Time Frame: Up to 2 years ]
    Disease control rate is defined as the percentage of participants with a confirmed best overall response of CR or PR or at least 12 weeks of stable disease per RECIST v 1.1.
  • Part 2: Disease Control Rate [ Time Frame: Up to 2 years ]
    Disease control rate is defined as the percentage of participants with a confirmed best overall response of CR or PR or at least 12 weeks of stable disease per RECIST v 1.1.
  • Part 1: Time to Response [ Time Frame: Up to 2 years ]
    Time to response is defined as the time from the date of first dose to the date of the first documented evidence of response (PR or CR).
  • Part 2: Time to Response [ Time Frame: Up to 2 years ]
    Time to response is defined as the time from the date of first dose to the date of the first documented evidence of response (PR or CR).
  • Part 1: Duration of Response [ Time Frame: Up to 2 years ]
    Duration of response is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause among participants who achieve an overall response (that is., a confirmed best overall response of CR or PR) by RECIST v 1.1.
  • Part 2: Duration of Response [ Time Frame: Up to 2 years ]
    Duration of response is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause among participants who achieve an overall response (that is., a confirmed best overall response of CR or PR) by RECIST v 1.1.
  • Part 1: Progression-free Survival [ Time Frame: Up to 2 years ]
    Progression-free survival is defined as the interval of time (in months) between the date of first dose to the date of disease progression according to clinical or radiological assessment or death due to any causes, whichever occurs earliest. PFS was determined according to RECIST version 1.1. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
  • Part 2: Progression-free Survival [ Time Frame: Up to 2 years ]
    Progression-free survival is defined as the interval of time (in months) between the date of first dose to the date of disease progression according to clinical or radiological assessment or death due to any causes, whichever occurs earliest by RECIST v 1.1. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
  • Part 1: Overall Survival [ Time Frame: Up to 27 months ]
    Overall survival is defined as time from the date of first dose of study treatment (whichever investigational drug administered first) to the date of death due to any cause.
  • Part 2: Overall Survival [ Time Frame: Up to 27 months ]
    Overall survival is defined as time from the date of first dose of study treatment (whichever investigational drug administered first) to the date of death due to any cause.
  • Part 1a: Plasma Concentration of GSK1795091 [ Time Frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Days 78, 162, 246, 414 and 498: 10 minutes post-dose ]
    Blood samples were collected at indicated time points for the determination of plasma concentration of GSK1795091. Pharmacokinetic (PK) Population consisted of all participants from the All Treated population for whom a PK sample was obtained, analyzed, measurable, and valid.
  • Part 1b: Plasma Concentration of GSK1795091 [ Time Frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose ]
    Blood samples were collected at indicated time points for the determination of plasma concentration of GSK1795091.
  • Part 1c: Plasma Concentration of GSK1795091 [ Time Frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose ]
    Blood samples were collected at indicated time points for the determination of plasma concentration of GSK1795091.
  • Part 1a: Maximum Plasma Concentration (Cmax) of GSK1795091 [ Time Frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Days 78, 162, 246, 414 and 498: 10 minutes post-dose ]
    Blood samples were collected at indicated time points for the determination of Cmax of GSK1795091.
  • Part 1b: Cmax of GSK1795091 [ Time Frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose ]
    Blood samples were collected at indicated time points for the determination of Cmax of GSK1795091.
  • Part 1c: Cmax of GSK1795091 [ Time Frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose ]
    Blood samples were collected at indicated time points for the determination of Cmax of GSK1795091.
  • Part 1a: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) GSK1795091 [ Time Frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Days 78, 162, 246, 414 and 498: 10 minutes post-dose ]
    Blood samples were collected at indicated time points for the determination of AUC(0-tau) of GSK1795091.
  • Part 1b: AUC(0-tau) GSK1795091 [ Time Frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose ]
    Blood samples were collected at indicated time points for the determination of AUC(0-tau) of GSK1795091.
  • Part 1c: AUC(0-tau) GSK1795091 [ Time Frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose ]
    Blood samples were collected at indicated time points for the determination of AUC(0-tau) of GSK1795091.
  • Part 1a: Predose Concentration (Cpre) of GSK1795091 [ Time Frame: Days 1, 8, 15, 22, 57, 64, 78, 162, 246, 414 and 498: Pre-dose ]
    Blood samples were collected at indicated time points for the determination of Cpre of GSK1795091.
  • Part 1b: Cpre of GSK1795091 [ Time Frame: Days 1, 8, 15, 22, 57, 64 and 78: Pre-dose ]
    Blood samples were collected at indicated time points for the determination of Cpre of GSK1795091.
  • Part 1c: Cpre of GSK1795091 [ Time Frame: Days 1, 8, 15, 22, 57, 64 and 78: Pre-dose ]
    Blood samples were collected at indicated time points for the determination of Cpre of GSK1795091.
  • Part 1a: Number of Participants With Present Antidrug Antibody (ADA) Against GSK3174998 [ Time Frame: Up to 27 months ]
    Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to GSK3174998. The presence of anti-GSK3174998 antibodies were assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
  • Part 1b: Number of Participants With the Present ADA Against GSK3359609 [ Time Frame: Up to 27 months ]
    Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to GSK3359609. The presence of anti-GSK3359609 antibodies were assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
  • Part 1c: Number of Participants With the Present ADA Against Pembrolizumab [ Time Frame: Up to 27 months ]
    Serum samples were collected at indicated time points for the presence of antibodies that bind to pembrolizumab. The presence of anti-pembrolizumab antibodies were planned to be assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
  • Part 2a: Number of Participants With the Present ADA Against GSK3174998 [ Time Frame: Up to 2 years ]
    Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to GSK3174998. The presence of anti-GSK3174998 antibodies were were planeed to be assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
  • Part 2b: Number of Participants With the Present ADA Against GSK3359609 [ Time Frame: Up to 2 years ]
    Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to GSK3359609. The presence of anti-GSK3359609 antibodies were were planeed to be assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
  • Part 2c: Number of Participants With the Present ADA Against Pembrolizumab [ Time Frame: Up to 2 years ]
    Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to pembrolizumab. The presence of anti-pembrolizumab antibodies were were planeed to be assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
Original Secondary Outcome Measures  ICMJE
 (submitted: February 21, 2018)
  • Objective response rate [ Time Frame: Up to 2 years ]
    Objective response rate is defined as percentage of subjects with complete response (CR) or partial response (PR). Objective response rate will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  • Disease control rate [ Time Frame: Up to 2 years ]
    Disease control rate is defined as percentage of subjects with CR or PR or at least 12 weeks of stable disease. Disease control rate will be evaluated according to RECIST 1.1.
  • Time to response [ Time Frame: Up to 2 years ]
    Time to response is defined as the time from the date of first dose to the date of the first documented evidence of response (PR or CR).
  • Duration of response [ Time Frame: Up to 2 years ]
    Duration of response is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause among subjects who achieve an overall response (that is, unconfirmed or confirmed CR or PR)
  • Number of subjects with progression-free survival (PFS) [ Time Frame: Up to 2 years ]
    PFS is defined as time from the date of first dose to the date of disease progression according to clinical or radiological assessment or death due to any causes, whichever occurs earliest.
  • Number of subjects with overall survival [ Time Frame: Up to 2 years ]
    Overall survival is defined as time from the date of first dose to the date of death due to any cause.
  • Plasma concentration of GSK3174998-Part 1 [ Time Frame: Day15 (pre-dose, 30minutes, 4hours post-dose), Day16 (24 hours post-dose), Day22, Day36 (pre-dose), Day57 (pre-dose, 30minutes, 4hours post-dose), Day58 (24hours post-dose), Day64, and pre-dose on Day78 and every 12weeks for 2years ]
    Blood samples will be collected at indicated time points for the determination of plasma concentration of GSK3174998. Pre-dose indicates blood sample will be collected within 60 minutes before the start of the GSK3174998 infusion.
  • Plasma concentration of GSK3174998-Part 2 [ Time Frame: Day 1 (pre-dose, 30 minutes, 4 hours post-dose), Day 8, Day 22 (pre-dose), Day 43 (pre-dose, 30 minutes, 4 hours post-dose), Day 50, pre-dose on Day 64, Day 85 and then every 12 weeks for 2 years ]
    Blood samples will be collected at indicated time points for the determination of plasma concentration of GSK3174998. Pre-dose indicates blood sample will be collected within 60 minutes before the start of the GSK3174998 infusion.
  • Plasma concentration of GSK1795091-Part 1 [ Time Frame: Day15 (pre-dose,10minutes,4hours post-dose),Day16 (24hours post-dose),Day22 (pre-dose),Day57 (pre-dose,10minutes,4hours post-dose),Day58 (24hours post-dose), Day64 (pre-dose,10minutes post-dose),10minutes post-dose on Day78 and every 12weeks for 2years ]
    Blood samples will be collected at indicated time points for the determination of plasma concentration of GSK1795091. Pre-dose indicates the blood sample will be collected within 60 minutes before the start of the GSK1795091 injection.
  • Plasma concentration of GSK1795091-Part 2 [ Time Frame: Day1 (pre-dose, 10minutes, 2, 4, 6hours post-dose), Day8 (pre-dose), Day22 (10minutes post-dose), Day43 (pre-dose, 10minutes, 4 hours post-dose), Day50 (pre-dose, 10minutes post-dose), 10minutes post-dose on Day64, Day85 and then every 12weeks for 2years ]
    Blood samples will be collected at indicated time points for the determination of plasma concentration of GSK1795091. Pre-dose indicates the blood sample will be collected within 60 minutes before the start of the GSK1795091 injection.
  • Maximum observed concentration (Cmax) of GSK3174998-Part 1 [ Time Frame: Day15 (pre-dose, 30minutes, 4hours post-dose), Day16 (24 hours post-dose), Day22, Day36 (pre-dose), Day57 (pre-dose, 30minutes, 4hours post-dose), Day58 (24hours post-dose), Day64, and pre-dose on Day78 and every 12weeks for 2years ]
    Blood samples will be collected at indicated time points for determination of Cmax. Pre-dose indicates blood sample will be collected within 60 minutes before the start of the GSK3174998 infusion.
  • Cmax of GSK3174998-Part 2 [ Time Frame: Day 1 (pre-dose, 30 minutes, 4 hours post-dose), Day 8, Day 22 (pre-dose), Day 43 (pre-dose, 30 minutes, 4 hours post-dose), Day 50, pre-dose on Day 64, Day 85 and then every 12 weeks for 2 years ]
    Blood samples will be collected at indicated time points for determination of Cmax. Pre-dose indicates blood sample will be collected within 60 minutes before the start of the GSK3174998 infusion.
  • Cmax of GSK1795091-Part 1 [ Time Frame: Day15 (pre-dose,10minutes,4hours post-dose),Day16 (24hours post-dose),Day22 (pre-dose),Day57 (pre-dose,10minutes,4hours post-dose),Day58 (24hours post dose), Day64 (pre-dose,10minutes post-dose),10minutes post-dose on Day78 and every 12weeks for 2years ]
    Blood samples will be collected at indicated time points for determination of Cmax. Pre-dose indicates the blood sample will be collected within 60 minutes before the start of the GSK1795091 injection.
  • Cmax of GSK1795091-Part 2 [ Time Frame: Day1 (pre-dose, 10minutes, 2, 4, 6hours post-dose), Day8 (pre-dose), Day22 (10minutes post-dose), Day43 (pre-dose, 10minutes, 4 hours post-dose), Day50 (pre-dose, 10minutes post-dose), 10minutes post-dose on Day64, Day85 and then every 12weeks for 2years ]
    Blood samples will be collected at indicated time points for determination of Cmax. Pre-dose indicates the blood sample will be collected within 60 minutes before the start of the GSK1795091 injection.
  • Area under the concentration-time curve over the dosing interval (AUC [0-tau]) of GSK3174998-Part 1 [ Time Frame: Day15 (pre-dose, 30minutes, 4hours post-dose), Day16 (24 hours post-dose), Day22, Day36 (pre-dose), Day57 (pre-dose, 30minutes, 4hours post-dose), Day58 (24hours post-dose), Day64, and pre-dose on Day78 and every 12weeks for 2years ]
    Blood samples will be collected at indicated time points for determination of AUC (0-tau). Pre-dose indicates blood sample will be collected within 60 minutes before the start of the GSK3174998 infusion.
  • AUC (0-tau) of GSK3174998-Part 2 [ Time Frame: Day 1 (pre-dose, 30 minutes, 4 hours post-dose), Day 8, Day 22 (pre-dose), Day 43 (pre-dose, 30 minutes, 4 hours post-dose), Day 50, pre-dose on Day 64, Day 85 and then every 12 weeks for 2 years ]
    Blood samples will be collected at indicated time points for determination of AUC (0-tau). Pre-dose indicates blood sample will be collected within 60 minutes before the start of the GSK3174998 infusion.
  • AUC (0-tau) of GSK1795091-Part 1 [ Time Frame: Day15 (pre-dose,10minutes,4hours post-dose),Day16 (24hours post-dose),Day22 (pre-dose),Day57 (pre-dose,10minutes,4hours post-dose),Day58 (24hours post-dose), Day64 (pre-dose,10minutes post-dose),10minutes post-dose on Day78 and every 12weeks for 2years ]
    Blood samples will be collected at indicated time points for determination of AUC (0-tau). Pre-dose indicates the blood sample will be collected within 60 minutes before the start of the GSK1795091 injection.
  • AUC (0-tau) of GSK1795091-Part 2 [ Time Frame: Day1 (pre-dose, 10minutes, 2, 4, 6hours post-dose), Day8 (pre-dose), Day22 (10minutes post-dose), Day43 (pre-dose, 10minutes, 4 hours post-dose), Day50 (pre-dose, 10minutes post-dose), 10minutes post-dose on Day64, Day85 and then every 12weeks for 2years ]
    Blood samples will be collected at indicated time points for determination of AUC (0-tau). Pre-dose indicates the blood sample will be collected within 60 minutes before the start of the GSK1795091 injection.
  • Trough plasma concentrations(Ctrough) of GSK3174998-Part 1 [ Time Frame: Day15 (pre-dose, 30minutes, 4hours post-dose), Day16 (24 hours post-dose), Day22, Day36 (pre-dose), Day57 (pre-dose, 30minutes, 4hours post-dose), Day58 (24hours post-dose), Day64, and pre-dose on Day78 and every 12weeks for 2years ]
    Blood samples will be collected at indicated time points for determination of Ctrough. Pre-dose indicates blood sample will be collected within 60 minutes before the start of the GSK3174998 infusion.
  • Ctrough of GSK3174998-Part 2 [ Time Frame: Day 1 (pre-dose, 30 minutes, 4 hours post-dose), Day 8, Day 22 (pre-dose), Day 43 (pre-dose, 30 minutes, 4 hours post-dose), Day 50, pre-dose on Day 64, Day 85 and then every 12 weeks for 2 years ]
    Blood samples will be collected at indicated time points for determination of Ctrough. Pre-dose indicates blood sample will be collected within 60 minutes before the start of the GSK3174998 infusion.
  • Ctrough of GSK1795091-Part 1 [ Time Frame: Day15 (pre-dose,10minutes,4hours post-dose),Day16 (24hours post-dose),Day22 (pre-dose),Day57 (pre-dose,10minutes,4hours post-dose),Day58 (24hours post-dose), Day64 (pre-dose,10minutes post-dose),10minutes post-dose on Day78 and every 12weeks for 2years ]
    Blood samples will be collected at indicated time points for determination of Ctrough. Pre-dose indicates the blood sample will be collected within 60 minutes before the start of the GSK1795091 injection.
  • Ctrough of GSK1795091-Part 2 [ Time Frame: Day1 (pre-dose, 10minutes, 2, 4, 6hours post-dose), Day8 (pre-dose), Day22 (10minutes post-dose), Day43 (pre-dose, 10minutes, 4 hours post-dose), Day50 (pre-dose, 10minutes post-dose), 10minutes post-dose on Day64, Day85 and then every 12weeks for 2years ]
    Blood samples will be collected at indicated time points for determination of Ctrough. Pre-dose indicates the blood sample will be collected within 60 minutes before the start of the GSK1795091 injection.
  • Number of subjects who develop detectable antidrug antibody (ADA) against GSK3174998 [ Time Frame: Up to 2 years ]
    Serum samples will be collected and tested for the presence of antibodies that bind to GSK3174998.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of a Combination of GSK1795091 and Immunotherapies in Subjects With Advanced Solid Tumors
Official Title  ICMJE A Phase I, Open-Label Study of GSK1795091 Administered in Combination With Immunotherapies in Participants With Advanced Solid Tumors
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
In Part 1, one dose level of GSK3174998, GSK3359609, or pembrolizumab with up to 5 dose levels of GSK1795091 are planned for evaluation. Sequential cohorts will be enrolled and dose escalation (or de-escalation) will proceed according to Neuenschwander-Continual Reassessment Method (N-CRM design). In Part 2, subjects will be administered GSK1795091 in combination with either 24 mg GSK3174998, 80 mg GSK3359609, or 200 mg pembrolizumab at a dose identified in Part 1.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasms
Intervention  ICMJE
  • Drug: GSK1795091
    GSK1795091 will be available as solution for injection
  • Drug: GSK3174998
    GSK3174998 will be available as lyophilized powder to be reconstituted for infusion.
  • Drug: GSK3359609
    GSK3359609 will be available as solution for infusion.
  • Drug: Pembrolizumab
    Pembrolizumab will be available as solution for infusion or lyophilized powder for reconstitution.
Study Arms  ICMJE
  • Experimental: Part 1a: 50ng GSK1795091 + 24mg GSK3174998
    Participants will be administered GSK1795091 50 nanogram (ng) intravenously (IV) on Days 1 and 8 followed by once weekly administration of GSK1795091 50 ng IV in combination with GSK3174998 24 milligram (mg) administered at 3-week intervals (Q3W) via the IV route until Week 12. From Week 12 onwards, GSK1795091 50 ng IV will be administered in combination with GSK3174998 24 mg at Q3W interval.
    Interventions:
    • Drug: GSK1795091
    • Drug: GSK3174998
  • Experimental: Part 1a: 100ng GSK1795091 + 24mg GSK3174998
    Participants will be administered GSK1795091 100 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 100 ng IV in combination with GSK3174998 24 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 100 ng IV will be administered in combination with GSK3174998 24 mg at Q3W interval.
    Interventions:
    • Drug: GSK1795091
    • Drug: GSK3174998
  • Experimental: Part 1a: 150ng GSK1795091 + 24mg GSK3174998
    Participants will be administered GSK1795091 150 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 150 ng IV in combination with GSK3174998 24 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 150 ng IV will be administered in combination with GSK3174998 24 mg at Q3W interval.
    Interventions:
    • Drug: GSK1795091
    • Drug: GSK3174998
  • Experimental: Part 1a: 200ng GSK1795091 + 24mg GSK3174998
    Participants will be administered GSK1795091 200 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 200 ng IV in combination with GSK3174998 24 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 200 ng IV will be administered in combination with GSK3174998 24 mg at Q3W interval.
    Interventions:
    • Drug: GSK1795091
    • Drug: GSK3174998
  • Experimental: Part 1a: 250ng GSK1795091 + 24mg GSK3174998
    Participants will be administered GSK1795091 250 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 250 ng IV in combination with GSK3174998 24 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 250 ng IV will be administered in combination with GSK3174998 24 mg at Q3W interval.
    Interventions:
    • Drug: GSK1795091
    • Drug: GSK3174998
  • Experimental: Part 1b: 50ng GSK1795091 + 80mg GSK3359609
    Participants will be administered GSK1795091 50 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 50 ng IV in combination with GSK3359609 80 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 50 ng IV will be administered in combination with GSK3359609 80 mg at Q3W interval.
    Interventions:
    • Drug: GSK1795091
    • Drug: GSK3359609
  • Experimental: Part 1b: 100ng GSK1795091 + 80mg GSK3359609
    Participants will be administered GSK1795091 100 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 100 ng IV in combination with GSK3359609 80 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 100 ng IV will be administered in combination with GSK3359609 80 mg at Q3W interval.
    Interventions:
    • Drug: GSK1795091
    • Drug: GSK3359609
    • Drug: Pembrolizumab
  • Experimental: Part 1b: 150ng GSK1795091 + 80mg GSK3359609
    Participants will be administered GSK1795091 150 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 150 ng IV in combination with GSK3359609 80 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 150 ng IV will be administered in combination with GSK3359609 80 mg at Q3W interval.
    Interventions:
    • Drug: GSK1795091
    • Drug: GSK3359609
  • Experimental: Part 1b: 200ng GSK1795091 + 80mg GSK3359609
    Participants will be administered GSK1795091 200 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 200 ng IV in combination with GSK3359609 80 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 200 ng IV will be administered in combination with GSK3359609 80 mg at Q3W interval.
    Interventions:
    • Drug: GSK1795091
    • Drug: GSK3359609
  • Experimental: Part 1b: 250ng GSK1795091 + 80mg GSK3359609
    Participants will be administered GSK1795091 250 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 250 ng IV in combination with GSK3359609 80 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 250 ng IV will be administered in combination with GSK3359609 80 mg at Q3W interval.
    Interventions:
    • Drug: GSK1795091
    • Drug: GSK3359609
  • Experimental: Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab
    Participants will be administered GSK1795091 50 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 50 ng IV in combination with pembrolizumab 200 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 50 ng IV will be administered in combination with pembrolizumab 200 mg at Q3W interval.
    Interventions:
    • Drug: GSK1795091
    • Drug: Pembrolizumab
  • Experimental: Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab
    Participants will be administered GSK1795091 100 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 100 ng IV in combination with pembrolizumab 200 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 100 ng IV will be administered in combination with pembrolizumab 200 mg at Q3W interval.
    Interventions:
    • Drug: GSK1795091
    • Drug: Pembrolizumab
  • Experimental: Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab
    Participants will be administered GSK1795091 150 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 150 ng IV in combination with pembrolizumab 200 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 150 ng IV will be administered in combination with pembrolizumab 200 mg at Q3W interval.
    Interventions:
    • Drug: GSK1795091
    • Drug: Pembrolizumab
  • Experimental: Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab
    Participants will be administered GSK1795091 200 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 200 ng IV in combination with pembrolizumab 200 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 200 ng IV will be administered in combination with pembrolizumab 200 mg at Q3W interval.
    Interventions:
    • Drug: GSK1795091
    • Drug: Pembrolizumab
  • Experimental: Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab
    Participants will be administered GSK1795091 250 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 250 ng IV in combination with pembrolizumab 200 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 250 ng IV will be administered in combination with pembrolizumab 200 mg at Q3W interval.
    Interventions:
    • Drug: GSK1795091
    • Drug: Pembrolizumab
  • Experimental: Part 2a: GSK1795091 + 24 mg GSK3174998
    Participants will be administered GSK1795091 at a dose identified in Part 1 along with GSK3174998 24 mg.
    Interventions:
    • Drug: GSK1795091
    • Drug: GSK3174998
  • Experimental: Part 2b: GSK1795091 + 80 mg GSK3359609
    Participants will be administered GSK1795091 at a dose identified in Part 1 along with GSK3359609 80 mg.
    Interventions:
    • Drug: GSK1795091
    • Drug: GSK3359609
  • Experimental: Part 2c: GSK1795091 + 200 mg Pembrolizumab
    Participants will be administered GSK1795091 at a dose identified in Part 1 along with pembrolizumab 200 mg.
    Interventions:
    • Drug: GSK1795091
    • Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 21, 2018)
54
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 11, 2022
Actual Primary Completion Date July 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subject must be >=18 years of at the time of signing the informed consent.
  • Histological documentation of advanced solid tumor.
  • Archival tumor tissue obtained at any time from the initial diagnosis to study entry. Although a fresh biopsy obtained during screening is preferred, archival tumor specimen is acceptable if it is not feasible to obtain a fresh biopsy. Subjects enrolled in a PK/Pharmacodynamic Cohort must provide a fresh biopsy of a tumor lesion not previously irradiated during the screening period and must agree to provide at least one additional on-treatment biopsy.
  • Disease that has progressed after standard therapies or for which standard therapy is otherwise unsuitable (example, intolerance).
  • Measurable disease, that is, presenting with at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
  • Life expectancy of at least 12 weeks.
  • Adequate organ function.
  • In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
  • Male or female subjects will be included. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: a) Not a woman of childbearing potential (WOCBP) OR b). A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions specified.

Additional Inclusion criteria for Subjects in Part 2a (GSK3174998 expansion) and Part 2b (GSK3359609 expansion):

  • Histological or cytological documentation of squamous cell carcinoma of the head and neck (SCCHN) (oral cavity, oropharynx, hypopharynx, or larynx) that is recurrent, locally advanced, or metastatic and is not amenable to curative treatment options, surgery or definitive chemoradiation therapy.
  • Received, ineligible for, or otherwise unsuitable for platinum-based therapy and anti-Programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy
  • Received no more than 3 prior lines of systemic therapy for metastatic disease.

Additional Inclusion Criteria for Subjects in Part 2c (pembrolizumab expansion):

  • Histological or cytological documentation of SCCHN (oral cavity, oropharynx, hypopharynx, or larynx) that is recurrent, locally advanced, or metastatic and is not amenable to curative treatment options, surgery or definitive chemoradiation therapy.
  • Received no more than 2 prior lines of systemic therapy for metastatic disease.

Exclusion Criteria:

  • Malignancy other than disease under study with the exception of those from which the subject has been disease-free for more than 2 years and not expected to affect the safety of the subject or the endpoints of the trial.
  • Symptomatic central nervous system (CNS) metastases or asymptomatic CNS metastases that have required steroids within 2 weeks prior to first dose of study treatment.
  • Active autoimmune disease that has required systemic disease modifying or immunosuppressive treatment within the last 2 years. Replacement therapy (example, thyroxine or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted.
  • Concurrent medical condition requiring the use of systemic immunosuppressive treatment within 28 days before the first dose of study treatment.
  • Known human immunodeficiency virus infection.
  • Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
  • Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study treatment.
  • Positive Hepatitis C test result at screening or within 3 months prior to first dose of study treatment.
  • QT interval corrected for heart rate according to Fridericia's formula (QTcF) >450 milliseconds (msec) or QTcF >480 msec for subjects with bundle branch block
  • Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction.
  • Recent history of allergen desensitization therapy within 4 weeks of starting study treatment.
  • History of severe hypersensitivity to monoclonal antibodies (mAbs).
  • History or evidence of cardiovascular (CV) risk including any of the following: a) Recent (within the past 6 months) history of serious uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities including second degree (Type II) or third degree atrioventricular block. b) Cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting, or bypass grafting within the past 6 months before enrollment. c) Congestive heart failure (Class II, III, or IV) as defined by the New York Heart Association (NYHA) functional classification system. d) Recent (within the past 6 months) history of symptomatic pericarditis.
  • History of idiopathic pulmonary fibrosis, pneumonitis, interstitial lung disease, or organizing pneumonia, or evidence of active, non-infectious pneumonitis.
  • Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural effusions.
  • Any serious and/or unstable pre-existing medical, psychiatric disorder, or other condition that could interfere with the subject's safety, obtaining informed consent, or compliance to the study procedures.
  • Is or has an immediate family member (example, spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective Institutional Review Board (IRB) approval (by chair or designee) is given allowing exception to this criterion for a specific subject.
  • Prior treatment with the following agents: a) OX40, inducible T-cell co-stimulator (ICOS) agonist at any time. b) Prior systemic or intratumoral therapy with TLR agonist. c) Anticancer therapy or investigational therapy within 30 days or 5 half-lives of the drug, whichever is shorter. d) Prior radiation therapy: permissible if at least 1 non-irradiated measurable lesion is available for assessment according to RECIST version 1.1 or if a solitary measurable lesion was irradiated, objective progression is documented. A wash out of at least 14 days before start of study treatment for radiation of any intended use to the extremities for bone metastases and 28 days for radiation to the chest, brain, or visceral organs is required.
  • Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.
  • Toxicity from previous treatment including: a) Toxicity Grade >=3 related to prior immunotherapy and that lead to study treatment discontinuation. b) Toxicity related to prior treatment has not resolved to Grade <=1 (except alopecia, or endocrinopathy managed with replacement therapy).
  • Received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony-stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor, and recombinant erythropoietin) within 2 weeks before the first dose of study treatment.
  • Major surgery <=4 weeks before the first dose of study treatment. Subjects must have also fully recovered from any surgery (major or minor) and/or its complications before initiating study treatment.
  • Known drug or alcohol abuse.
  • Receipt of any live vaccine within 4 weeks.

Additional Exclusion Criteria for Subjects in Part 2c

  • Received prior anti-PD-1/PD-L1 therapy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Netherlands,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03447314
Other Study ID Numbers  ICMJE 204686
2017-003545-23 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Iqvia Pty Ltd
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP