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Dose Escalation and Expansion Study of GSK3359609 in Participants With Selected Advanced Solid Tumors (INDUCE-1)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02723955
Recruitment Status : Recruiting
First Posted : March 31, 2016
Last Update Posted : September 4, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE March 24, 2016
First Posted Date  ICMJE March 31, 2016
Last Update Posted Date September 4, 2020
Actual Study Start Date  ICMJE June 23, 2016
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 22, 2020)
  • Part 1: Number of participants with any adverse event(s) (AE) [ Time Frame: Up to 27 months ]
    AE 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.
  • Part 1: Number of participants with serious adverse event(s) (SAE) [ Time Frame: Up to 27 months ]
    An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant or associated with liver injury and impaired liver function.
  • Part 1: Number of participants with dose limiting toxicity (DLT) [ Time Frame: Up to 28 days ]
    A DLT is defined as an AE that meets at least one of the criteria listed in protocol, according to National Cancer Institute (NCI) common terminology criteria for AE (CTCAE) version 4.0, and is considered by the investigator to be clinically relevant and attributed (probably, or possibly) to the study treatment during the first 28 days after the first dose of study treatment.
  • Part 1: Change from Baseline in systolic and diastolic blood pressure (Millimeter of mercury) [ Time Frame: Baseline and up to 24 months ]
    Systolic and diastolic blood pressure (Millimeter of mercury) will be measured in semi-supine position after 5 minutes of rest.
  • Part 1: Change from Baseline in pulse rate (Beats per minute) [ Time Frame: Baseline and up to 24 months ]
    Pulse rate (Beats per minute) will be measured in semi-supine position after 5 minutes of rest.
  • Part 1: Change from Baseline in body temperature (Degrees Celsius) [ Time Frame: Baseline and up to 24 months ]
    Body temperature (Degrees Celsius) will be measured in semi-supine position after 5 minutes of rest.
  • Part 1: Change from Baseline in hemoglobin (Grams per liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in hemoglobin (Grams per liter) will be analyzed.
  • Part 1: Change from Baseline in hematocrit (Proportion of red blood cells in blood) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in hematocrit (Proportion of red blood cells in blood) will be analyzed.
  • Part 1: Change from Baseline in red blood cell (RBC) count (Trillion cells per liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in RBC (Trillion cells per liter) will be analyzed.
  • Part 1: Change from Baseline in platelet count (Giga cells per Liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in platelet count (Giga cells per Liter) will be analyzed.
  • Part 1: Change from Baseline in white blood cell (WBC) count (Giga cells per Liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in WBC count (Giga cells per Liter) will be analyzed.
  • Part 1: Change from Baseline in total neutrophils, eosinophils, monocytes, basophils and lymphocytes (Giga cells per Liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in total neutrophils, eosinophils, monocytes, basophils, and lymphocytes (Giga cells per Liter) will be analyzed.
  • Part 1: Change from Baseline in blood urea nitrogen (BUN) (Millimoles per Liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in BUN (Millimoles per Liter) will be analyzed.
  • Part 1: Change from Baseline in creatinine and bilirubin (Micromoles per liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in creatinine and bilirubin (Micromoles per liter) will be analyzed.
  • Part 1: Change from Baseline in glucose, calcium, sodium and potassium (Millimoles per liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in glucose, calcium, sodium and potassium (Millimoles per liter) will be analyzed.
  • Part 1: Change from Baseline in total protein and albumin (Grams per liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in total protein and albumin (Grams per liter) will be analyzed.
  • Part 1: Change from Baseline in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) (International units per liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in AST, ALT and ALP (International units per liter) will be analyzed.
  • Part 1: Number of participants with any abnormal findings in urine analysis parameters [ Time Frame: Up to 24 months ]
    The following urinalysis parameters will be measured: potential of hydrogen (pH), glucose, protein, blood, ketones by dipstick and specific gravity.
  • Part 1: Change from Baseline in Troponin I or Troponin T (nanograms per liter) [ Time Frame: Baseline and up to 24 months ]
    Troponin I or Troponin T will be assessed by echocardiogram or multigated acquisition scans (MUGA) (nanograms per liter).
  • Part 1: Change from Baseline in thyroid stimulating hormone (TSH) (milliunits per liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in TSH (milliunits per liter) will be analyzed.
  • Part 1: Change from Baseline in triiodothyronine (T3) and thyroxine (T4) (nanograms per deciliter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in T3 and T4 (nanograms per deciliter) will be analyzed.
  • Part 1: Number of participants requiring dose modifications [ Time Frame: Up to 24 months ]
    All dose modifications due to any reason(s) will be recorded.
  • Part 2: Number of participants with any AEs [ Time Frame: Up to 27 months ]
    AE 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.
  • Part 2: Number of participants with serious adverse event(s) (SAE) [ Time Frame: Up to 27 months ]
    An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant or associated with liver injury and impaired liver function.
  • Part 2: Number of participants with DLT [ Time Frame: Up to 28 days ]
    A DLT is defined as an AE that meets at least one of the criteria listed in protocol, according to NCI CTCAE version 4.0, and is considered by the investigator to be clinically relevant and attributed (probably, or possibly) to the study treatment during the first 28 days after the first dose of study treatment.
  • Part 2: Change from Baseline in systolic and diastolic blood pressure (Millimeter of mercury) [ Time Frame: Baseline and up to 24 months ]
    Systolic and diastolic blood pressure (Millimeter of mercury) will be measured in semi-supine position after 5 minutes of rest.
  • Part 2: Change from Baseline in pulse rate (Beats per minute) [ Time Frame: Baseline and up to 24 months ]
    Pulse rate (beats per minute) will be measured in semi-supine position after 5 minutes of rest.
  • Part 2: Change from Baseline in body temperature (Degrees Celsius) [ Time Frame: Baseline and up to 24 months ]
    Body temperature (Degrees Celsius) will be measured in semi-supine position after 5 minutes of rest.
  • Part 2: Change from Baseline in hemoglobin (Grams per liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in haemoglobin (Grams per liter) will be analyzed.
  • Part 2: Change from Baseline in hematocrit (Proportion of red blood cells in blood) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in hematocrit (Proportion of red blood cells in blood) will be analyzed.
  • Part 2: Change from Baseline in RBC count (Trillion cells per liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in RBC (Trillion cells per liter) will be analyzed.
  • Part 2: Change from Baseline in platelet count (Giga cells per Liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in platelet (Giga cells per Liter) count will be analyzed.
  • Part 2: Change from Baseline in WBC count (Giga cells per Liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in WBC (Giga cells per Liter) count will be analyzed.
  • Part 2: Change from Baseline in total neutrophils, eosinophils, monocytes, basophils, and lymphocytes (Giga cells per Liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in total neutrophils, eosinophils, monocytes, basophils, and lymphocytes (Giga cells per Liter) will be analyzed.
  • Part 2: Change from Baseline in BUN (Millimoles per Liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in BUN (Millimoles per Liter) will be analyzed.
  • Part 2: Change from Baseline in creatinine and bilirubin (Micromoles per liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in creatinine and bilirubin (Micromoles per liter) will be analyzed.
  • Part 2: Change from Baseline in glucose, calcium, sodium and potassium (Millimoles per liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in glucose, calcium, sodium and potassium (Millimoles per liter) will be analyzed.
  • Part 2: Change from Baseline in total protein and albumin (Grams per liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in total protein and albumin (Grams per liter) will be analyzed.
  • Part 2: Change from Baseline in AST, ALT and ALP (International units per liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in AST, ALT and ALP (International units per liter) will be analyzed.
  • Part 2: Number of participants with any abnormal findings in urine analysis parameters [ Time Frame: Up to 24 months ]
    The following urinalysis parameters will be measured: pH, glucose, protein, blood, ketones by dipstick and specific gravity.
  • Part 2: Change from Baseline in Troponin I or Troponin T (nanograms per liter) [ Time Frame: Baseline and up to 24 months ]
    Troponin I or Troponin T will be assessed by echocardiogram or MUGA (nanograms per liter).
  • Part 2: Change from Baseline in TSH (milliunits per liter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in TSH (milliunits per liter) will be analyzed.
  • Part 2: Change from Baseline in T3 and T4 (nanograms per deciliter) [ Time Frame: Baseline and up to 24 months ]
    Blood samples will be collected at indicated time points and change from Baseline in T3 and T4 (nanograms per deciliter) will be analyzed.
  • Part 2: Number of participants requiring dose modifications [ Time Frame: Up to 24 months ]
    All dose modifications due to any reason(s) will be recorded.
Original Primary Outcome Measures  ICMJE
 (submitted: March 24, 2016)
  • Parts 1 and 2: Number of subjects with any adverse event(s) (AE) and serious adverse event(s) (SAE) [ Time Frame: Up to 27 months ]
  • Parts 1 and 2: Changes in systolic and diastolic blood pressure [ Time Frame: Up to 24 months ]
  • Parts 1 and 2: Changes in pulse rate [ Time Frame: Up to 24 months ]
  • Parts 1 and 2: Changes in temperature [ Time Frame: Up to 24 months ]
  • Parts 1 and 2: Change in hematology parameters [ Time Frame: Up to 24 months ]
    The following hematology parameters will be measured: hemoglobin, Hematocrit, Red blood cell (RBC) count, Platelet count, white blood cell (WBC) count, Total neutrophils (Absolute), Eosinophils (Absolute), Monocytes (Absolute), Basophils (Absolute), and Lymphocytes (Absolute)
  • Parts 1 and 2: Change in chemistry parameters [ Time Frame: Up to 24 months ]
    The following chemistry parameters will be measured: Blood Urea nitrogen (BUN), Creatinine, Glucose, Calcium, Sodium, Potassium, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Bilirubin, Total protein and Albumin.
  • Parts 1 and 2: Change in urinalysis parameters [ Time Frame: Up to 24 months ]
    The following urinalysis parameters will be measured: pH, Glucose, Protein, Blood, Ketones by dipstick; and specific gravity
  • Parts 1 and 2: Change in thyroid function tests [ Time Frame: Up to 24 months ]
  • Parts 1 and 2: Number subject requiring dose modifications [ Time Frame: Up to 24 months ]
  • Parts 1 and 2: Number subject with dose limiting toxicity (DLT) [ Time Frame: First 28 days after the first dose of study treatment ]
    A DLT is defined as an AE that meets at least one of the criteria listed in protocol, according to National Cancer Institute (NCI) common terminology criteria for AE (CTCAE) grade (G) version 4.0, and is considered by the investigator to be clinically relevant and attributed (definitely, probably, or possibly) to the study treatment during the first 28 days after the first dose of study treatment.
  • Parts 1 and 2: Pharmacodynamic characteristics assessed as a measures of target engagement and functional effects in the tumor and in the periphery [ Time Frame: Up to 24 months ]
  • Parts 1 and 2: Plasma concentrations of GSK3359609 [ Time Frame: Days 1, 2, 3, 5, 8, 15, 22, 29, 36, 43, 64, 85, 106, 127 and Week 21 from then every 12 weeks, and additionally at 30 days and 12 weeks post last dose of GSK3359609 (Up to 27 months). ]
  • Part 2: Plasma concentrations of pembrolizumab [ Time Frame: Days 1, 2, 8, 15, 22, 64, 106, 127 and Week 21 from then every 12 weeks, and additionally at 30 days and 12 weeks post last dose of Pembrolizumab (Up to 27 months). ]
  • Parts 1 and 2: Change in echocardiogram [ Time Frame: Up to 24 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2020)
  • Part 1: Disease control rate (DCR) [ Time Frame: Up to 27 months ]
    DCR is defined as the percentage of participants with a confirmed complete response (CR) + partial response (PR) at any time, plus stable disease (SD) >=18 weeks.
  • Part 1: Overall survival (OS) [ Time Frame: up to 4 years ]
    OS is defined as time from the date of first dose of study treatment to the date of death due to any cause.
  • Part 1: Progression-free survival (PFS) [ Time Frame: Up to 27 months ]
    PFS is defined as time from the date of first dose of study treatment to the date of disease progression according to clinical or radiographic assessment or death due to any cause, whichever occurs earliest.
  • Part 1: Time to overall response (TTR) [ Time Frame: Up to 27 months ]
    TTR will be summarized for participants with a confirmed CR or PR and is defined as the time from date of first dose of study treatment to date of first documented confirmed CR or PR.
  • Part 1: Duration of response (DOR) [ Time Frame: Up to 27 months ]
    DOR will be summarized for participants with a confirmed CR or PR and is defined as the time from date of initial confirmed response to the date of disease progression or death due to any cause.
  • Part 1: Overall response rate (ORR) [ Time Frame: Up to 27 months ]
    ORR is defined as the percentage of participants with a best overall confirmed CR or a PR at any time as per disease-specific criteria.
  • Part 1: Maximum observed plasma concentration (Cmax) of GSK3359609 [ Time Frame: Day1:predose,end of infusion(EOI),EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Day 8 and 15,Day22:pre EOI+4hours,Days29and 36,Days43 to 106:pre EOI+4hours,Day127:pre dose;Week21 then every12weeks postdose(Up to 27months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmax.
  • Part 1: Minimum observed plasma concentration (Cmin) of GSK3359609 [ Time Frame: Day1:predose,end of infusion(EOI),EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Day 8 and 15,Day22:pre EOI+4hours,Days29and 36,Days43 to 106:pre EOI+4hours,Day127:pre dose;Week21 then every12weeks postdose(Up to 27months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmin.
  • Part 1: Area under the concentration-time curve over the dosing interval (AUC[0-tau]) of GSK3359609 in plasma [ Time Frame: Day1:predose,end of infusion(EOI),EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Day 8 and 15,Day22:pre EOI+4hours,Days29and 36,Days43 to 106:pre EOI+4hours,Day127:pre dose;Week21 then every12weeks postdose(Up to 27months) ]
    Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
  • Part 1: Number of participants with positive results in Anti-drug antibody (ADA) test by GSK3359609 dose level [ Time Frame: Up to 27 months ]
    Blood samples will be collected up to 27 months for ADA test.
  • Part 1: Number of participants with positive results in GSK3359609 [ Time Frame: Up to 27 months ]
    Blood samples will be collected up to 27 months for immunogenicity.
  • Part 2: Number of participants with DLT following administration of GSK3359609 combination with chemotherapies [ Time Frame: Up to 28 days ]
    A DLT is defined as an AE that meets at least one of the criteria listed in protocol, according to NCI CTCAE G version 4.0, and is considered by the investigator to be clinically relevant and attributed (probably, or possibly) to the study treatment during the first 28 days after the first dose of study treatment.
  • Part 2: Disease control rate (DCR) [ Time Frame: Up to 27 months ]
    DCR is defined as the percentage of participants with a confirmed CR + PR at any time, plus SD >=18 weeks.
  • Part 2: Overall survival (OS) [ Time Frame: Up to 4 years ]
    OS is defined as time from the date of first dose of study treatment to the date of death due to any cause.
  • Part 2: Progression-free survival (PFS) [ Time Frame: Up to 27 months ]
    PFS is defined as time from the date of first dose of study treatment to the date of disease progression according to clinical or radiographic assessment or death due to any cause, whichever occurs earliest.
  • Part 2: Time to overall response (TTR) [ Time Frame: Up to 27 months ]
    TTR will be summarized for participants with a confirmed CR or PR and is defined as the time from date of first dose of study treatment to date of first documented confirmed CR or PR.
  • Part 2: Duration of response (DOR) [ Time Frame: Up to 27 months ]
    DOR will be summarized for participants with a confirmed CR or PR and is defined as the time from date of initial confirmed response to the date of disease progression or death due to any cause.
  • Part 2: Overall response rate (ORR) [ Time Frame: Up to 27 months ]
    ORR is defined as the percentage of participants with a best overall confirmed CR or a PR at any time as per disease-specific criteria.
  • Part 2: Cmax of GSK3359609 (Q3W dosing) [ Time Frame: Day1:predose,EOI,EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Day 8 and 15, Day22:pre EOI+4hours,Days29 and 36,Days43 to 106:pre EOI+4hours,Day127:pre dose;Week21 then every 12weeks postdose (Up to 27months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmax.
  • Part 2: Cmin of GSK3359609 (Q3W dosing) [ Time Frame: Day1:predose,EOI,EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Day 8 and 15, Day22:pre EOI+4hours,Days29 and 36,Days43 to 106:pre EOI+4hours,Day127:pre dose;Week21 then every 12weeks postdose (Up to 27months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmin.
  • Part 2: AUC(0-tau) of GSK3359609 (Q3W dosing) [ Time Frame: Day1:predose,EOI,EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Day 8 and 15, Day22:pre EOI+4hours,Days29 and 36,Days43 to 106:pre EOI+4hours,Day127:pre dose;Week21 then every 12weeks postdose (Up to 27months) ]
    Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
  • Part 2: Cmax of GSK3174998 [ Time Frame: Day 1: predose, EOI, EOI+4 hours, EOI+24 hours, Day 8 and 15, Day22: predose, Day 43:predose, EOI,EOI+4hours, Day 64 and 85: predose, EOI+4hours, Day 106: predose,Day127:pre dose;Week21 then every 12weeks postdose (Up to 24months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmax.
  • Part 2: Cmin of GSK3174998 [ Time Frame: Day 1: predose, EOI, EOI+4 hours, EOI+24 hours, Day 8 and 15, Day22: predose, Day 43:predose, EOI,EOI+4hours, Day 64 and 85: predose, EOI+4hours, Day 106: predose,Day127:pre dose;Week21 then every 12weeks postdose (Up to 24months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmin.
  • Part 2: AUC(0-tau) of GSK3174998 [ Time Frame: Day 1: predose, EOI, EOI+4 hours, EOI+24 hours, Day 8 and 15, Day22: predose, Day 43:predose, EOI,EOI+4hours, Day 64 and 85: predose, EOI+4hours, Day 106: predose,Day127:pre dose;Week21 then every 12weeks postdose (Up to 24months) ]
    Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
  • Part 2: Cmax of Pembrolizumab (Q3W dosing) [ Time Frame: Day 1: pre-dose, EOI + 30 minutes, Day 2: EOI+24 hours, Days 8 and 15, Days 22, 43, 85, and 106: predose, Days 29, 36 and 64, Day 127: predose, and Week 21 then every 12 weeks postdose (Up to 27 months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmax.
  • Part 2: Cmin of Pembrolizumab (Q3W dosing) [ Time Frame: Day 1: pre-dose, EOI + 30 minutes, Day 2: EOI+24 hours, Days 8 and 15, Days 22, 43, 85, and 106: predose, Days 29, 36 and 64, Day 127: predose, and Week 21 then every 12 weeks postdose (Up to 27 months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmin.
  • Part 2: AUC(0-tau) of Pembrolizumab (Q3W dosing) [ Time Frame: Day 1: pre-dose, EOI + 30 minutes, Day 2: EOI+24 hours, Days 8 and 15, Days 22, 43, 85, and 106: predose, Days 29, 36 and 64, Day 127: predose, and Week 21 then every 12 weeks postdose (Up to 27 months) ]
    Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
  • Part 2: Number of participants with positive results in ADA test by GSK3359609 in combination with pembrolizumab or GSK3174998 dose level [ Time Frame: Up to 27 months ]
    Blood samples will be collected up to 27 months for ADA test.
  • Part 2: Number of participants with positive results in Pembrolizumab [ Time Frame: Up to 27 months ]
    Blood samples will be collected up to 27 months for immunogenicity.
  • Part 2: Number of participants with positive results in GSK3174998 [ Time Frame: Up to 27 months ]
    Blood samples will be collected up to 27 months for immunogenicity.
  • Part 2: Cmax of GSK3359609 combination with chemotherapies [ Time Frame: Day 1: predose, EOI, EOI+2 hours, EOI+4 hours, Days 22, 64, 106, and 127: EOI, EOI+ 2 hours post chemotherapy (Up to 27 months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmax.
  • Part 2: Cmin of GSK3359609 combination with chemotherapies [ Time Frame: Day 1: predose, EOI, EOI+2 hours, EOI+4 hours, Days 22, 64, 106, and 127: EOI, EOI+ 2 hours post chemotherapy (Up to 27 months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmin.
  • Part 2: Number of participants with positive results in ADA test by GSK3359609 combination with chemotherapies dose level [ Time Frame: Up to 27 months ]
    Blood samples will be collected up to 27 months for ADA test.
  • Part 2: Cmax of GSK3359609 (Q6W dosing) [ Time Frame: Day1:predose,EOI,EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Days 8, 15, 22, 29 and 36:pre dose,Days43 and 85:pre EOI+4hours,Days 64,106 and 127:pre dose;Week21 then every12weeks postdose (Up to 27months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmax.
  • Part 2: Cmin of GSK3359609 (Q6W dosing) [ Time Frame: Day1:predose,EOI,EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Days 8, 15, 22, 29 and 36:pre dose,Days43 and 85:pre EOI+4hours,Days 64,106 and 127:pre dose;Week21 then every 12weeks postdose (Up to 27months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmin.
  • Part 2: AUC(0-tau) of GSK3359609 (Q6W dosing) [ Time Frame: Day1:predose,EOI,EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Days 8, 15, 22, 29 and 36:pre dose,Days43 and 85:pre EOI+4hours,Days 64,106 and 127:pre dose;Week21 then every12weeks postdose (Up to 27months) ]
    Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
  • Part 2: Cmax of Pembrolizumab (Q6W dosing) [ Time Frame: Day 1: pre-dose, EOI + 30 minutes, Day 2: EOI+24 hours, Day 8, 15, 22, 29, 36, 64 and 106, Days 43, 85 and 127: predose, and Week 21 then every 12 weeks postdose (Up to 27 months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmax.
  • Part 2: Cmin of Pembrolizumab (Q6W dosing) [ Time Frame: Day 1: pre-dose, EOI + 30 minutes, Day 2: EOI+24 hours, Day 8, 15, 22, 29, 36, 64 and 106, Days 43, 85 and 127: predose, and Week 21 then every 12 weeks postdose (Up to 27 months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmin.
  • Part 2: AUC(0-tau) of Pembrolizumab (Q6W dosing) [ Time Frame: Day 1: pre-dose, EOI + 30 minutes, Day 2: EOI+24 hours, Day 8, 15, 22, 29, 36, 64 and 106, Days 43, 85 and 127: predose, and Week 21 then every 12 weeks postdose (Up to 27 months) ]
    Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
  • Part 2: Cmax of dostarlimab [ Time Frame: Day 1, 22, 85 and 127: pre-dose, EOI, then pre-dose every 18 weeks (Up to 27 months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmax.
  • Part 2: Cmin of dostarlimab [ Time Frame: Day 1, 22, 85 and 127: pre-dose, EOI, then pre-dose every 18 weeks (Up to 27 months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmin.
  • Part 2: AUC(0-tau) of dostarlimab [ Time Frame: Day 1, 22, 85 and 127: pre-dose, EOI, then pre-dose every 18 weeks (Up to 27 months) ]
    Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
  • Part 2: Cmax of cobolimab [ Time Frame: Days 1, 22, 43, 64, 85, 106 and 127: pre-dose, EOI + 0.5 hours then pre-dose every 18 weeks (Up to 27 months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmax
  • Part 2: Cmin of cobolimab [ Time Frame: Days 1, 22, 43, 64, 85, 106 and 127: pre-dose, EOI + 0.5 hours then pre-dose every 18 weeks (Up to 27 months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmin.
  • Part 2: AUC(0-tau) of cobolimab [ Time Frame: Days 1, 22, 43, 64, 85, 106 and 127: pre-dose, EOI + 0.5 hours then pre-dose every 18 weeks (Up to 27 months) ]
    Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
  • Part 2: Cmax of bintrafusp alfa [ Time Frame: Day 1: pre-dose, EOI, EOI + 30 minutes, Day 2: EOI+24 hours, Days 8 and 15, Days 22, 43, 64, 85, 106: pre-dose, EOI; Day 127: pre-dose and pre-dose at Week 21 then every 12 weeks (Up to 27 months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmax.
  • Part 2: Cmin of bintrafusp alfa [ Time Frame: Day 1: pre-dose, EOI, EOI + 30 minutes, Day 2: EOI+24 hours, Days 8 and 15, Days 22, 43, 64, 85, 106: pre-dose, EOI; Day 127: pre-dose and pre-dose at Week 21 then every 12 weeks (Up to 27 months) ]
    Blood samples will be collected at the indicated time points for evaluation of Cmin.
  • Part 2: AUC(0-tau) of bintrafusp alfa [ Time Frame: Day 1: pre-dose, EOI, EOI + 30 minutes, Day 2: EOI+24 hours, Days 8 and 15, Days 22, 43, 64, 85, 106: pre-dose, EOI; Day 127: pre-dose and pre-dose at Week 21 then every 12 weeks (Up to 27 months) ]
    Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
Original Secondary Outcome Measures  ICMJE
 (submitted: March 24, 2016)
  • Parts 1 and 2: Disease control rate (DCR) [ Time Frame: Up to 24 months ]
    DCR is defined as the percentage of subjects with a confirmed complete response (CR) + partial response (PR) at any time, plus stable disease (SD) >=18 weeks)
  • Parts 1 and 2: Overall response rate (ORR) [ Time Frame: Up to 24 months ]
    ORR is defined as the percentage of subjects with a best overall confirmed CR or a PR at any time as per disease-specific criteria
  • Parts 1 and 2: Overall survival (OS) [ Time Frame: up to 4 years ]
    OS is defined as time from the date of first dose of study treatment to the date of death due to any cause.
  • Parts 1 and 2: Progression-free survival (PFS) [ Time Frame: Up to 24 months ]
    PFS is defined as time from the date of first dose of study treatment to the date of disease progression according to clinical or radiographic assessment or death due to any cause, whichever occurs earliest.
  • Parts 1 and 2: Time to overall response (TTR) [ Time Frame: Up to 24 months ]
    TTR will be summarized for subjects with a confirmed CR or PR and is defined as the time from date of first dose of study treatment to date of first documented confirmed CR or PR.
  • Parts 1 and 2: Duration of response (DOR) [ Time Frame: Up to 24 months ]
    DOR will be summarized for subjects with a confirmed CR or PR and is defined as the time from date of initial confirmed response to the date of disease progression or death due to any cause.
  • Part 1: Anti-drug antibody (ADA) incidence by GSK3359609 dose level [ Time Frame: Up to 27 months ]
  • Part 2: ADA incidence by GSK3359609 and pembrolizumab dose level [ Time Frame: Up to 27 months ]
  • Parts 1 and 2: Area under curve (AUC) from time curve over the dosing interval [ Time Frame: Days 1, 2, 3, 5, 8, 15, 22, 29, 36, 43, 64, 85, 106, 127 and Week 21 from then every 12 weeks, and additionally at 30 days and 12 weeks post last dose of GSK3359609 (Up to 27 months) ]
  • Parts 1 and 2: Maximum observed plasma concentration (Cmax) of GSK3359609 [ Time Frame: Days 1, 2, 3, 5, 8, 15, 22, 29, 36, 43, 64, 85, 106, 127 and Week 21 from then every 12 weeks, and additionally at 30 days and 12 weeks post last dose of GSK3359609 (Up to 27 months). ]
  • Part 1 and 2: Minimum observed plasma concentration (Cmin) of GSK3359609 [ Time Frame: Days 1, 2, 3, 5, 8, 15, 22, 29, 36, 43, 64, 85, 106, 127 and Week 21 from then every 12 weeks, and additionally at 30 days and 12 weeks post last dose of GSK3359609 (Up to 27 months). ]
  • Parts 1 and 2: AUC (0-tau) of Pembrolizumab [ Time Frame: Days 1, 2, 8, 15, 22, 64, 106, 127 and Week 21 from then every 12 weeks, and additionally at 30 days and 12 weeks post last dose of Pembrolizumab (Up to 27 months) ]
  • Parts 1 and 2: Cmax of Pembrolizumab [ Time Frame: Days 1, 2, 8, 15, 22, 64, 106, 127 and Week 21 from then every 12 weeks, and additionally at 30 days and 12 weeks post last dose of Pembrolizumab (Up to 27 months). ]
  • Parts 1 and 2: Cmin of Pembrolizumab [ Time Frame: Days 1, 2, 8, 15, 22, 64, 106, 127 and Week 21 from then every 12 weeks, and additionally at 30 days and 12 weeks post last dose of Pembrolizumab (Up to 27 months). ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose Escalation and Expansion Study of GSK3359609 in Participants With Selected Advanced Solid Tumors (INDUCE-1)
Official Title  ICMJE A Phase I Open Label Study of GSK3359609 Administered Alone and in Combination With Anticancer Agents in Subjects With Selected Advanced Solid Tumors
Brief Summary GSK3359609 is an anti-Inducible T cell Co-Stimulator (ICOS) receptor agonist antibody intended for the treatment of cancers of different histology. This is a first-time-in-human (FTIH), open-label, multicenter study designed to investigate the safety, pharmacology, and preliminary antitumor activity in participants with selected, advanced or recurrent solid tumors with the aim to establish recommended dose(s) of GSK3359609 for further exploration as monotherapy and in combination with pembrolizumab, chemotherapy or other immune therapies. The study is comprised of two primary parts, each composed of two phases: Part 1: GSK3359609 monotherapy with Part 1A as dose escalation phase and Part 1B as cohort expansion phase; Part 2: GSK3359609 combination therapy with Part 2A pembrolizumab or GSK3174998 or dostarlimab or dostarlimab plus cobolimab or Bintrafusp alfa combination dose escalation phase and Part 2B expansion phase with pembrolizumab. Part 2A GSK3359609 combinations with chemotherapy will only consist of safety run-in cohorts. Each part and phase of the study includes a screening period, a treatment period, and a follow-up period. The primary objective of the study is to determine the safety, tolerability, maximum tolerated dose or the maximum administered dose of GSK3359609 alone or in combination.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasms
Intervention  ICMJE
  • Drug: GSK3359609 IV infusion
    GSK3359609 diluted product will be administered as an IV infusion to participants Q3W or Q6W.
  • Drug: GSK3174998 IV infusion
    GSK3174998 diluted product will be administered as an IV infusion to participants Q3W.
  • Drug: Pembrolizumab 200 mg IV infusion
    Pembrolizumab 200 mg will be administered as an IV infusion to participants Q3W.
  • Drug: Docetaxel 75 milligrams per square meters (mg/m^2) IV infusion
    Docetaxel 75 mg/m^2 diluted product will be administered as an IV infusion to participants Q3W.
  • Drug: Pemetrexed 500 mg/m^2 plus Carboplatin area under the curve (AUC) 4-6 mg/mL per minute IV infusion
    Pemetrexed 500 mg/m^2 diluted product in combination with Carboplatin AUC 4-6 milligram per milliliter (mg/mL) per minute (diluted product), will be administered as an IV infusion to participants Q3W.
  • Drug: Paclitaxel 200 mg/m^2 plus Carboplatin AUC 4-6 mg/mL per minute IV infusion
    Paclitaxel 200 mg/m^2 diluted product in combination with Carboplatin AUC 4-6 mg/mL per minute (diluted product), will be administered as an IV infusion to participants Q3W.
  • Drug: Gemcitabine 1250 mg/m^2 plus Carboplatin AUC 4-6 mg/mL per minute IV infusion
    Gemcitabine 1250 mg/m^2 diluted product in combination with Carboplatin AUC 4-6 mg/mL per minute (diluted product), will be administered as an IV infusion to participants Q3W.
  • Drug: Fluorouracil (5-FU) 1000 mg/m^2/day plus carboplatin or cisplatin
    Carboplatin AUC 4-6 mg/mL per minute or cisplatin at 100 mg/m^2 will be combined with 5-FU at 1000 mg/m^2/day will be administered as an IV infusion to participants Q3W.
  • Drug: Pembrolizumab 400 mg IV infusion
    Pembrolizumab 400 mg will be administered as an IV infusion to participants Q6W.
  • Drug: Dostarlimab
    Dostarlimab will be administered as an IV infusion at a dose of 500 mg once Q3W for 4 doses followed by a dose of 1000 mg Q6W.
  • Drug: Cobolimab
    Cobolimab will be administered as an IV infusion at a dose of 300 mg Q3W.
  • Drug: Bintrafusp alfa
    Bintrafusp alfa will be administered as an IV infusion at a dose of 2400 mg Q3W.
Study Arms  ICMJE
  • Experimental: Part 1A: Dose escalation GSK3359609
    Participants will receive GSK3359609 as an intravenous (IV) infusion administered once every 3 weeks (Q3W) continuously at a dose level dependent on to which dose level the participant is accrued.
    Intervention: Drug: GSK3359609 IV infusion
  • Experimental: Part 1B: Expansion GSK3359609
    Participants will receive GSK3359609 as an IV infusion administered Q3W continuously at a dose level chosen for further exploration in dose expansion cohorts.
    Intervention: Drug: GSK3359609 IV infusion
  • Experimental: Part 2A: Dose escalation (GSK3359609+pembrolizumab)
    Participants will receive GSK3359609 as an IV infusion administered Q3W continuously in combination with 200 milligram (mg) of pembrolizumab as an IV infusion administered once Q3W continuously.
    Interventions:
    • Drug: GSK3359609 IV infusion
    • Drug: Pembrolizumab 200 mg IV infusion
  • Experimental: Part 2A: Dose escalation (GSK3359609+GSK3174998)
    Participants will receive GSK3359609 as an IV infusion administered Q3W continuously in combination with GSK3174998 as an IV infusion administered once Q3W.
    Interventions:
    • Drug: GSK3359609 IV infusion
    • Drug: GSK3174998 IV infusion
  • Experimental: Part 2A: Safety run-in (GSK3359609+chemotherapy)
    Participants participating in Part 2A chemotherapy combination cohorts will receive GSK3359609 in combination with chemotherapy at doses and schedules based on standard of care practice.
    Interventions:
    • Drug: GSK3359609 IV infusion
    • Drug: Docetaxel 75 milligrams per square meters (mg/m^2) IV infusion
    • Drug: Pemetrexed 500 mg/m^2 plus Carboplatin area under the curve (AUC) 4-6 mg/mL per minute IV infusion
    • Drug: Paclitaxel 200 mg/m^2 plus Carboplatin AUC 4-6 mg/mL per minute IV infusion
    • Drug: Gemcitabine 1250 mg/m^2 plus Carboplatin AUC 4-6 mg/mL per minute IV infusion
    • Drug: Fluorouracil (5-FU) 1000 mg/m^2/day plus carboplatin or cisplatin
  • Experimental: Part 2A: Dose escalation (GSK3359609+ dostarlimab)
    Participants will receive GSK3359609 as an IV infusion administered Q3W continuously in combination with dostarlimab administered as an IV infusion at 500 mg Q3W for 4 cycles followed by 1000 mg Q6W.
    Interventions:
    • Drug: GSK3359609 IV infusion
    • Drug: Dostarlimab
  • Experimental: Part 2A: Dose escalation (GSK3359609+dostarlimab+cobolimab)
    Participants will receive GSK3359609 as an IV infusion administered Q3W continuously in combination with dostarlimab administered as an IV infusion at 500 mg Q3W for 4 cycles followed by 1000 mg Q6W plus cobolimab administered as an IV infusion at 300 mg Q3W.
    Interventions:
    • Drug: GSK3359609 IV infusion
    • Drug: Dostarlimab
    • Drug: Cobolimab
  • Experimental: Part 2A: Dose escalation (GSK3359609+bintrafusp alfa)
    Participants will receive GSK3359609 as an IV infusion administered Q3W continuously in combination with bintrafusp alfa administered as an IV infusion at 2400 mg Q3W.
    Interventions:
    • Drug: GSK3359609 IV infusion
    • Drug: Bintrafusp alfa
  • Experimental: Part 2B: Expansion-GSK3359609
    Participants will receive GSK3359609 as an IV infusion administered Q3W continuously in combination with 200 mg of pembrolizumab as an IV infusion administered once Q3W continuously.
    Interventions:
    • Drug: GSK3359609 IV infusion
    • Drug: Pembrolizumab 200 mg IV infusion
  • Experimental: Part 2B: Expansion-GSK3359609 (Q6W)
    Participants will receive GSK3359609 as an IV infusion administered once every 6 weeks (Q6W) continuously in combination with 400 mg of pembrolizumab as an IV infusion administered Q6W continuously.
    Interventions:
    • Drug: GSK3359609 IV infusion
    • Drug: Pembrolizumab 400 mg IV infusion
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 22, 2020)
873
Original Estimated Enrollment  ICMJE
 (submitted: March 24, 2016)
304
Estimated Study Completion Date  ICMJE December 31, 2024
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • Capable of giving signed, written informed consent.
  • Male or female, age >=18 years (at the time consent is obtained).
  • Histological or cytological documentation of an invasive malignancy that was diagnosed as locally advanced/metastatic or relapsed/refractory and is of one of the following tumor types: bladder/urothelial cancer of the upper and lower urinary tract; cervical; colorectal (includes appendix); esophagus, squamous cell; head and neck carcinoma; melanoma; malignant pleural mesothelioma (MPM); non-small-cell lung cancer (NSCLC), prostate; Microsatellite Instability-High/deficient mismatch repair (MSI-H/dMMR) tumor (Part 1B and Part 2B) and Human Papilloma Virus (HPV)-positive or Epstein-Barr (EBV)-positive tumor (Part 1B and Part 2B).
  • Disease that has progressed after standard therapy for the specific tumor type, or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate, or if no further standard therapy exists; exceptions are in these tumor types in which pembrolizumab single agent may be a standard: NSCLC, head and neck squamous cell cancer (HNSCC), bladder/urothelial cancer, MSI-H/dMMR cancers and melanoma and cervical cancer. In Part 2B pembrolizumab combination expansion cohorts, prior treatment with anti-Programmed cell death protein 1(PD-1)/ Ligand-1 (L1) may not be required. 1) Participants must not have received more than 5 prior lines of therapy for advanced disease including both standards of care and investigational therapies. 2) Participants who received prior PD-1/L1 therapy must fulfill the following requirements (Part 1B [except PK/PD cohort]/ Part 2B):a) Have achieved a CR, PR or SD and subsequently had disease progression while still on PD-1/L1 therapy; b) Have received at least 2 doses of an approved PD-1/L1 inhibitor (by any regulatory authority), c) Have demonstrated disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 within 18 weeks from the last dose of the PD-1/L1 inhibitor. The initial evidence of disease progression is to be confirmed by a second assessment no less than four weeks from the date of the first documented Progressive Disease (PD) (the confirmatory scan could be the Baseline eligibility scan for this study). 3) In Part 2A 5-fluorouracil (FU)/platinum combination with GSK3359609 and pembrolizumab cohort, participants must not have received prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy given as part of multimodal treatment for locally advanced disease).
  • Archival tumor tissue obtained at any time from the initial diagnosis to study entry; a fresh tumor biopsy using a procedure that is safe for the participant on a lesion not previously irradiated unless lesion progressed will be required if archival tissue is unavailable.
  • Agree to undergo a pre-treatment and on treatment biopsy and have disease amenable to biopsy required in pharmacokinetic (PK) / pharmacodynamics (PD), dose randomized HNSCC, Melanoma dose expansion and Biomarker cohorts..
  • Measurable disease per RECIST version 1.1. Palpable lesions that are not measurable by radiographic or photographic evaluations may not be utilized as the only measurable lesion. Any measurable lesion biopsied at Screening cannot be followed as a target/index lesion unless agreed upon by GlaxoSmithKline (GSK).
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
  • Life expectancy of at least 12 weeks.
  • Adequate organ function.
  • QT interval corrected for heart rate according to Fridericia's formula (QTcF) <450 milliseconds (msec) or QTcF <480 msec for participants with bundle branch block.
  • A female participant is eligible to participate if she is not pregnant (as confirmed by a negative serum beta-human chorionic gonadotrophin [beta-hCG] test in females of reproductive potential), and not lactating or reproductive potential agrees to follow one of the options listed in protocol from 30 days prior to the first dose of study medication and until 120 days after the last dose of study treatment.
  • Male participants with female partners of child bearing potential must agree to use one of the methods of contraception specified in protocol from time of first dose of study treatment until 120 days after the last dose of study treatment.
  • Documented HPV/ EBV-positive tumor as determined by a local laboratory for Part 1B and Part 2B pembrolizumab combination viral-positive expansion cohorts only.
  • Documented MSI-H or dMMR-positive tumor as determined by local laboratory for Part 1B and Part 2B pembrolizumab combination MSI-H/dMMR expansion cohorts only.
  • Documented ICOS expression using an analytically validated immunohistochemistry (IHC) assay by central laboratory for Part 1B biomarker cohort only.
  • Documented gene expression (GEX) result using an analytically validated method by central laboratory (Part 1B Biomarker Cohort only).
  • PD-L1 combined positive score (CPS) <1 using the Food and Drug Administration (FDA) approved PD-L1 IHC 22C3 pharmdx assay by central laboratory testing for Part 2B HNSCC PD-L1 CPS <1 Cohort. Documented test result from FDA approved PD-L1 IHC 22C3 pharmDx assay in local laboratory, if available, may be accepted in lieu of the central laboratory test result.
  • Defined PD-L1 expression using the Ventana PD-L1 (SP263) IHC assay by central testing for enrollment in the PK/PD cohort with bintrafusp alfa, dostarlimab, dostarlimab and cobolimab combination studies (Part 2A).

Exclusion Criteria

  • Prior treatment with the following therapies:

    • Anticancer therapy within 30 days or 5 half-lives of the drug, whichever is shorter. At least 14 days must have elapsed between the last dose of prior anticancer agent and the first dose of study drug is administered.
    • Part 2B (GSK3359609/pembrolizumab combination): prior pembrolizumab washout is not required.
    • Prior radiation therapy: permissible if at least one 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 two weeks before start of study drug for radiation of any intended use to the extremities for bone metastases and 4 weeks for radiation to the chest, brain, or visceral organs is required. • Investigational therapy within 30 days or 5 half-lives of the investigational product (whichever is shorter). At least 14 days must have elapsed between the last dose of investigational agent and the first dose of study drug is administered.
  • Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.
  • Toxicity from previous anticancer treatment
  • Invasive malignancy or history of invasive malignancy other than disease under study within the last two years except: Any other invasive malignancy for which the participant was definitively treated, has been disease-free for <=2 years and in the opinion of the principal investigator and GSK Medical Monitor will not affect the evaluation of the effects of the study treatment on the currently targeted malignancy, may be included in this clinical trial; and curatively treated non-melanoma skin cancer.
  • Central nervous system (CNS) metastases, with the following exception: • Participants who have previously-treated CNS metastases, are asymptomatic, and have no requirement for steroids at least 14 days prior to first dose of study drug. Participants with carcinomatous meningitis or leptomeningeal spread are excluded regardless of clinical stability.
  • 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, recombinant erythropoietin) within 14 days prior to the first dose of GSK3359609.
  • Major surgery <=4 weeks before the first dose of study treatment. Participants must have also fully recovered from any surgery (major or minor) and/or its complications before initiating study treatment.
  • Active autoimmune disease that has required systemic treatment within the last two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Concurrent medical condition requiring the use of systemic immunosuppressive medications within 7 days before the first dose of study treatment. Physiologic doses of corticosteroids for treatment of endocrinopathies or steroids with minimal systemic absorption, including topical, inhaled, or intranasal corticosteroids may be continued if the participant is on a stable dose.
  • Condition requiring treatment with strong inhibitors/inducers of cytochrome (CYP) p450 3A4 within 7 days prior to first dose of chemotherapy (requirement applies to participants enrolled to Part 2 chemotherapy combination with docetaxel).
  • Active infection requiring systemic therapy, known human immunodeficiency virus infection, or positive test for hepatitis B active infection or hepatitis C active infection.
  • Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease per investigator assessment).
  • Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction that required surgery.
  • Receipt of any live vaccine within 4 weeks prior to first dose of study treatment.
  • Recent history of allergen desensitization therapy within 4 weeks of starting study treatment.
  • History of severe hypersensitivity to monoclonal antibodies or to the chemotherapies under investigation including any ingredient used in the formulation.
  • History or evidence of cardiac abnormalities.
  • History of (current and past) idiopathic pulmonary fibrosis, pneumonitis (for past pneumonitis exclusion only if steroids were required for treatment), interstitial lung disease, or organizing pneumonia. Note: post-radiation changes in the lung related to prior radiotherapy and/or asymptomatic radiation-induced pneumonitis not requiring treatment may be permitted if agreed by the investigator and Medical Monitor.
  • 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 participant's safety, obtaining informed consent, or compliance to the study procedures.
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: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com
Listed Location Countries  ICMJE Australia,   Canada,   France,   Italy,   Japan,   Netherlands,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02723955
Other Study ID Numbers  ICMJE 204691
2016-000148-32 ( 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 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 Merck Sharp & Dohme Corp.
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date September 2020

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