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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 : May 27, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
GlaxoSmithKline

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.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: GSK3359609 IV infusion Drug: GSK3174998 IV infusion Drug: Pembrolizumab 200 mg 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 Drug: Pembrolizumab 400 mg IV infusion Drug: Dostarlimab Drug: Cobolimab Drug: Bintrafusp alfa Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 873 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Open Label Study of GSK3359609 Administered Alone and in Combination With Anticancer Agents in Subjects With Selected Advanced Solid Tumors
Actual Study Start Date : June 23, 2016
Estimated Primary Completion Date : December 19, 2022
Estimated Study Completion Date : December 19, 2022

Arm Intervention/treatment
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.
Drug: GSK3359609 IV infusion
GSK3359609 diluted product will be administered as an IV infusion to participants Q3W or Q6W.

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.
Drug: GSK3359609 IV infusion
GSK3359609 diluted product will be administered as an IV infusion to participants Q3W or Q6W.

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.
Drug: GSK3359609 IV infusion
GSK3359609 diluted product will be administered as an IV infusion to participants Q3W or Q6W.

Drug: Pembrolizumab 200 mg IV infusion
Pembrolizumab 200 mg will be administered as an IV infusion to participants Q3W.

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.
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.

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.
Drug: GSK3359609 IV infusion
GSK3359609 diluted product will be administered as an IV infusion to participants Q3W or Q6W.

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.

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.
Drug: GSK3359609 IV infusion
GSK3359609 diluted product will be administered as an IV infusion to participants Q3W or 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.

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.
Drug: GSK3359609 IV infusion
GSK3359609 diluted product will be administered as an IV infusion to participants Q3W or 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.

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.
Drug: GSK3359609 IV infusion
GSK3359609 diluted product will be administered as an IV infusion to participants Q3W or Q6W.

Drug: Bintrafusp alfa
Bintrafusp alfa will be administered as an IV infusion at a dose of 2400 mg Q3W.

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.
Drug: GSK3359609 IV infusion
GSK3359609 diluted product will be administered as an IV infusion to participants Q3W or Q6W.

Drug: Pembrolizumab 200 mg IV infusion
Pembrolizumab 200 mg will be administered as an IV infusion to participants Q3W.

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.
Drug: GSK3359609 IV infusion
GSK3359609 diluted product will be administered as an IV infusion to participants Q3W or Q6W.

Drug: Pembrolizumab 400 mg IV infusion
Pembrolizumab 400 mg will be administered as an IV infusion to participants Q6W.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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).

  20. 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.

  21. 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.

  22. 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.

  23. 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.

  24. 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.

  25. 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.

  26. 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.

  27. 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.

  28. 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.

  29. 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.

  30. 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.

  31. 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.

  32. 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.

  33. 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.

  34. 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.

  35. 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.

  36. 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.

  37. 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.

  38. 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.

  39. 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.

  40. 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.

  41. 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).

  42. 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.

  43. 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.

  44. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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).

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 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).

  22. 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.

  23. 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.

  24. 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).

  25. 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.

  26. 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.

  27. 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).

  28. 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.

  29. 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.

  30. 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.

  31. 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.

  32. 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.

  33. 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.

  34. 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.

  35. 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.

  36. 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).

  37. 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.

  38. 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.

  39. 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).

  40. 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.

  41. 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.

  42. 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).

  43. 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

  44. 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.

  45. 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).

  46. 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.

  47. 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.

  48. 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02723955


Contacts
Layout table for location contacts
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

Locations
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United States, California
GSK Investigational Site Recruiting
Duarte, California, United States, 91010
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Erminia Massarelli         
GSK Investigational Site Recruiting
Los Angeles, California, United States, 90025
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Ani Balmanoukian         
United States, Florida
GSK Investigational Site Recruiting
Sarasota, Florida, United States, 34232
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Judy S Wang         
United States, New York
GSK Investigational Site Recruiting
New York, New York, United States, 10016
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Daniel Cho         
GSK Investigational Site Recruiting
New York, New York, United States, 10032
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Matthen Mathew         
United States, Oklahoma
GSK Investigational Site Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Raid Aljumaily         
United States, Pennsylvania
GSK Investigational Site Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Anthony J Olszanski         
United States, Tennessee
GSK Investigational Site Recruiting
Nashville, Tennessee, United States, 37203
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Todd M Bauer         
GSK Investigational Site Recruiting
Nashville, Tennessee, United States, 37232-6307
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Leora Horn         
Australia, Victoria
GSK Investigational Site Recruiting
Heidelberg, Victoria, Australia, 3084
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Hui Gan         
GSK Investigational Site Recruiting
Melbourne, Victoria, Australia, 3000
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Danny Rischin         
Australia, Western Australia
GSK Investigational Site Recruiting
Nedlands, Western Australia, Australia, 6009
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Michael Millward         
Canada, Ontario
GSK Investigational Site Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Aaron Hansen         
France
GSK Investigational Site Recruiting
Bordeaux Cedex, France, 33076
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Antoine Italiano         
GSK Investigational Site Recruiting
Lyon cedex 08, France, 69373
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Catherine Terret         
GSK Investigational Site Recruiting
Paris, France, 75005
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Christophe Le Tourneau         
GSK Investigational Site Recruiting
Villejuif cedex, France, 94805
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Eric Angevin         
Italy
GSK Investigational Site Recruiting
Siena, Toscana, Italy, 53100
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Michele Maio         
Japan
GSK Investigational Site Recruiting
Chiba, Japan, 277-8577
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Yasutoshi Kuboki         
GSK Investigational Site Recruiting
Osaka, Japan, 589-8511
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Masayuki Takeda         
GSK Investigational Site Recruiting
Tokyo, Japan, 104-0045
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Noboru Yamamoto         
Netherlands
GSK Investigational Site Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Frans L. Opdam         
Spain
GSK Investigational Site Recruiting
Barcelona, Spain, 08035
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Elena Garralda Cabanas         
GSK Investigational Site Recruiting
Barcelona, Spain, 08036
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Ana Arance Fernández         
GSK Investigational Site Recruiting
Madrid, Spain, 28040
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Victor Moreno García         
GSK Investigational Site Recruiting
Málaga, Spain, 29010
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Jose Manuel Trigo Pérez         
GSK Investigational Site Recruiting
Sevilla, Spain, 41009
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: David Vicente Baz         
Sponsors and Collaborators
GlaxoSmithKline
Merck Sharp & Dohme Corp.
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02723955    
Other Study ID Numbers: 204691
2016-000148-32 ( EudraCT Number )
First Posted: March 31, 2016    Key Record Dates
Last Update Posted: May 27, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
ICOS receptor agonist antibody
Pembrolizumab
KEYNOTE-478
GSK3359609
Cohort expansion
Dose escalation
Dostarlimab
Cobolimab
Bintrafusp alfa
Additional relevant MeSH terms:
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Gemcitabine
Paclitaxel
Docetaxel
Carboplatin
Fluorouracil
Pembrolizumab
Pemetrexed
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors