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

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ClinicalTrials.gov Identifier: NCT02528357
Recruitment Status : Completed
First Posted : August 19, 2015
Results First Posted : May 18, 2021
Last Update Posted : May 18, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:

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

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

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


Condition or disease Intervention/treatment Phase
Neoplasms Drug: GSK3174998 Drug: Pembrolizumab Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 141 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label Study of GSK3174998 Administered Alone and in Combination With Anticancer Agents Including Pembrolizumab in Subjects With Selected Advanced Solid Tumors
Actual Study Start Date : September 11, 2015
Actual Primary Completion Date : April 29, 2020
Actual Study Completion Date : April 29, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1A: GSK3174998 Monotherapy- Dose escalation
Participants will receive GSK3174998 intravenously (IV) (dose range 0.003 to 10.0 milligram per kilogram [mg/kg]) every 3 weeks (Q3W) for up to 2 years or 35 cycles, whichever comes first.
Drug: GSK3174998
Lyophilized powder 40 mg reconstituted to get a dose range of 0.003 to <=10 mg/kg to be given as IV infusion for 30 minutes (min), Q3W

Experimental: Part 2A: GSK3174998+ pembrolizumab - Dose escalation
Participants will receive GSK3174998 IV (dose range 0.003 to 10.0 mg/kg) Q3W for up to 2 years or 35 cycles, whichever comes first + Pembrolizumab 200 mg IV Q3W for up to 2 years or 35 cycles, whichever comes first.
Drug: GSK3174998
Lyophilized powder 40 mg reconstituted to get a dose range of 0.003 to <=10 mg/kg to be given as IV infusion for 30 minutes (min), Q3W

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

Experimental: Part 2B: GSK3174998+ pembrolizumab - Cohort expansion
Participants will receive GSK3174998 IV (at one dose level shown to be tolerable in dose escalation of part 2A) Q3W for up to 2 years or 35 cycles, whichever comes first + Pembrolizumab 200 mg IV Q3W for 2 years or 35 cycles, whichever comes first.
Drug: GSK3174998
Lyophilized powder 40 mg reconstituted to get a dose range of 0.003 to <=10 mg/kg to be given as IV infusion for 30 minutes (min), Q3W

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




Primary Outcome Measures :
  1. Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) [ Time Frame: Up to maximum 39 weeks ]
    An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE.

  2. Part 2A: Number of Participants With Any SAE and Non-SAE [ Time Frame: Up to maximum 105 weeks ]
    An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE.

  3. Part 2B: Number of Participants With Any SAE and Non-SAE [ Time Frame: Up to maximum 33 weeks ]
    An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE.

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

  5. Part 2A: Number of Participants With DLTs [ Time Frame: 28 days ]
    An adverse event was considered as DLT if it was considered by the investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment, occurred within the first 28 days of the treatment, and met 1 of the following criteria: Hematologic: Febrile neutropenia, Grade4 neutropenia of >7days requiring Granulocyte colony-stimulating factor (G-CSF), Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding as described in National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of >=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT.

  6. Part 2B: Number of Participants With DLTs [ Time Frame: 28 days ]
    An adverse event was considered as DLT if it was considered by the investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment, occurred within the first 28 days of the treatment, and met 1 of the following criteria: Hematologic: Febrile neutropenia, Grade4 neutropenia of >7days requiring Granulocyte colony-stimulating factor (G-CSF), Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding as described in National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of >=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT.

  7. Part 1: Number of Participants With Any Adverse Event Leading to Withdrawal (AELD) From the Study [ Time Frame: Up to maximum 39 weeks ]
    An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any adverse event leading to withdrawal from the study is presented.

  8. Part 2A: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study [ Time Frame: Up to maximum 105 weeks ]
    An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any adverse event leading to withdrawal from the study is presented.

  9. Part 2B: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study [ Time Frame: Up to maximum 33 weeks ]
    An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any adverse event leading to withdrawal from the study is presented.

  10. Part 1: Number of Participants With Dose Reductions or Delay [ Time Frame: Up to maximum 39 weeks ]
    Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented.

  11. Part 2A: Number of Participants With Dose Reductions or Delay [ Time Frame: Up to maximum 105 weeks ]
    Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented.

  12. Part 2B: Number of Participants With Dose Reductions or Delay [ Time Frame: Up to maximum 33 weeks ]
    Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented.

  13. Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters [ Time Frame: Baseline (Day 1) and up to maximum 39 weeks ]
    Blood samples were collected for the analysis of following hematology parameters: hemoglobin (Hb), leukocyte count (leuko.), lymphocyte count (Lymph.), neutrophil count (Neutro.) and platelet count (PC). The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.

  14. Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters [ Time Frame: Baseline (Day 1) and up to maximum 105 weeks ]
    Blood samples were collected for the analysis of following hematology parameters: Hb, leuko., Lymph., Neutro. and PC. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.

  15. Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters [ Time Frame: Baseline (Day 1) and up to maximum 33 weeks ]
    Blood samples were collected for the analysis of following hematology parameters: Hb, leuko., Lymph., Neutro. and PC. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.

  16. Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters [ Time Frame: Baseline (Day 1) and up to maximum 39 weeks ]
    Blood samples were collected for the analysis of following liver function laboratory parameters: alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.

  17. Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters [ Time Frame: Baseline (Day 1) and up to maximum 105 weeks ]
    Blood samples were collected for the analysis of following liver function laboratory parameters: ALT, ALP, AST and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.

  18. Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters [ Time Frame: Baseline (Day 1) and up to maximum 33 weeks ]
    Blood samples were collected for the analysis of following liver function laboratory parameters: ALT, ALP, AST and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.

  19. Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [ Time Frame: Baseline (Day 1) and up to maximum 39 weeks ]
    SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: <120 millimeter mercury (mmHg); Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: >=160 mmHg. For DBP: Grade 0: <80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: >=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.

  20. Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP [ Time Frame: Baseline (Day 1) and up to maximum 105 weeks ]
    SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: <120 mmHg; Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: >=160 mmHg. For DBP: Grade 0: <80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: >=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.

  21. Part 2B: Number of Participants With Any Grade Change From Baseline in SBP and DBP [ Time Frame: Baseline (Day 1) and up to maximum 33 weeks ]
    SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: <120 mmHg; Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: >=160 mmHg. For DBP: Grade 0: <80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: >=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.

  22. Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) [ Time Frame: Baseline (Day 1) and up to maximum 39 weeks ]
    Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: <60 beats per minute [bpm]', normal HR: 60 to 100 bpm and high HR: >100 bpm. If values were unchanged (example: increase to >100 bpm to increase to >100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.

  23. Part 2A: Number of Participants With Worst Case Change From Baseline in HR [ Time Frame: Baseline (Day 1) and up to maximum 105 weeks ]
    Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: <60 bpm', normal HR: 60 to 100 bpm and high HR: >100 bpm. If values were unchanged (example: increase to >100 bpm to increase to >100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.

  24. Part 2B: Number of Participants With Worst Case Change From Baseline in HR [ Time Frame: Baseline (Day 1) and up to maximum 33 weeks ]
    Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: <60 bpm', normal HR: 60 to 100 bpm and high HR: >100 bpm. If values were unchanged (example: increase to >100 bpm to increase to >100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.

  25. Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature [ Time Frame: Baseline (Day 1) and up to maximum 39 weeks ]
    Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: <=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: >=38 degrees Celsius. If values were unchanged (example: increase to >=38 degrees Celsius to increase to >=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.

  26. Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature [ Time Frame: Baseline (Day 1) and up to maximum 105 weeks ]
    Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: <=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: >=38 degrees Celsius. If values were unchanged (example: increase to >=38 degrees Celsius to increase to >=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.

  27. Part 2B: Number of Participants With Worst Case Change From Baseline in Body Temperature [ Time Frame: Baseline (Day 1) and up to maximum 33 weeks ]
    Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: <=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: >=38 degrees Celsius. If values were unchanged (example: increase to >=38 degrees Celsius to increase to >=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.

  28. Part 1: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant Electrocardiogram (ECG) Findings [ Time Frame: Up to maximum 39 weeks ]
    A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented.

  29. Part 2A: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings [ Time Frame: Up to maximum 105 weeks ]
    A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented.

  30. Part 2B: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings [ Time Frame: Up to maximum 33 weeks ]
    A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented.


Secondary Outcome Measures :
  1. Part 1: Objective Response Rate (ORR) [ Time Frame: Up to maximum 39 weeks ]
    ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or a partial response (PR) as the Best Overall Response (BOR), as assessed by the investigator per Response Evaluation Criteria In Solid Tumors (RECIST) Version (v) 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30 percent (%) decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart.

  2. Part 2A: Objective Response Rate (ORR) [ Time Frame: Up to maximum 105 weeks ]
    ORR is defined as the percentage of participants achieving a confirmed CR or PR as the BOR, as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart.

  3. Part 2B: Objective Response Rate (ORR) [ Time Frame: Up to maximum 33 weeks ]
    ORR is defined as the percentage of participants achieving a confirmed CR or PR as the BOR, as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart.

  4. Part 1: Disease Control Rate (DCR) [ Time Frame: Up to maximum 39 weeks ]
    DCR is defined as the percentage of participants with a confirmed CR or PR at any time, plus stable disease (SD) >=12 weeks as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. SD: 30% decrease in tumor burden compared with Baseline cannot be established nor 20% increase compared with nadir.

  5. Part 2A: Disease Control Rate (DCR) [ Time Frame: Up to maximum 105 weeks ]
    DCR is defined as the percentage of participants with a confirmed CR or PR at any time, plus SD >=12 weeks as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. SD: 30% decrease in tumor burden compared with Baseline cannot be established nor 20% increase compared with nadir.

  6. Part 2B: Disease Control Rate (DCR) [ Time Frame: Up to maximum 33 weeks ]
    DCR is defined as the percentage of participants with a confirmed CR or PR at any time, plus SD >=12 weeks as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. SD: 30% decrease in tumor burden compared with Baseline cannot be established nor 20% increase compared with nadir.

  7. Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points [ Time Frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion ]
    Blood samples for pharmacokinetic (PK) analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion (EOI); anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion.

  8. Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points [ Time Frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion ]
    Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion (EOI); anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion.

  9. Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points [ Time Frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion ]
    Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion (EOI); anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion.

  10. Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998 [ Time Frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) ]
    Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.

  11. Part 2A: AUC(0-tau) of GSK3174998 [ Time Frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) ]
    Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.

  12. Part 2B: AUC(0-tau) of GSK3174998 [ Time Frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) ]
    Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.

  13. Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 [ Time Frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) ]
    Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.

  14. Part 2A: Cmax and Cmin of GSK3174998 [ Time Frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) ]
    Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.

  15. Part 2B: Cmax and Cmin of GSK3174998 [ Time Frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) ]
    Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.

  16. Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points [ Time Frame: Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22, 64, 106 ]
    Blood samples for PK analysis of pembrolizumab were collected on Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion (EOPI); anytime on Days 8,15; Pre-dose on Days 22, 64, 106.

  17. Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points [ Time Frame: Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22, 64, 106 ]
    Blood samples for PK analysis of pembrolizumab were collected on Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15; Pre-dose on Days 22, 64, 106.

  18. Part 2A: AUC(0-tau) of Pembrolizumab [ Time Frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days) ]
    Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.

  19. Part 2B: AUC(0-tau) of Pembrolizumab [ Time Frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days) ]
    Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.

  20. Part 2A: Cmax of Pembrolizumab [ Time Frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days) ]
    Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.

  21. Part 2B: Cmax of Pembrolizumab [ Time Frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days) ]
    Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.

  22. Part 2A: Cmin of Pembrolizumab [ Time Frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days) ]
    Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.

  23. Part 2B: Cmin of Pembrolizumab [ Time Frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days) ]
    Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.

  24. Part 1: Number of Participants With Positive Antidrug Antibodies (ADAs) Against GSK3174998 [ Time Frame: Up to maximum 39 weeks ]
    Serum samples were collected for the determination of anti-GSK3174998 antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a GSK3174998 bridging style ADA assay with a bio-analytically determined cut-point determined during assay validation. Samples taken after dosing with GSK3174998 that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-GSK3174998 antibodies results at any visit during the study have been presented.

  25. Part 2A: Number of Participants With Positive ADAs Against GSK3174998 [ Time Frame: Up to maximum 105 weeks ]
    Serum samples were collected for the determination of anti-GSK3174998 antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a GSK3174998 bridging style ADA assay with a bio-analytically determined cut-point (determined during assay validation). Samples taken after dosing with GSK3174998 that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-GSK3174998 antibodies results at any visit during the study have been presented.

  26. Part 2B: Number of Participants With Positive ADAs Against GSK3174998 [ Time Frame: Up to maximum 33 weeks ]
    Serum samples were collected for the determination of anti-GSK3174998 antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a GSK3174998 bridging style ADA assay with a bio-analytically determined cut-point (determined during assay validation). Samples taken after dosing with GSK3174998 that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-GSK3174998 antibodies results at any visit during the study have been presented.

  27. Part 2A: Number of Participants With Positive ADAs Against Pembrolizumab [ Time Frame: Up to maximum 105 weeks ]
    Serum samples were collected for the determination of anti-pembrolizumab antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a pembrolizumab bridging style ADA assay with a bio-analytically determined cut-point (determined during assay validation). Samples taken after dosing with pembrolizumab that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-pembrolizumab antibodies results at any visit during the study have been presented.

  28. Part 2B: Number of Participants With Positive ADAs Against Pembrolizumab [ Time Frame: Up to maximum 33 weeks ]
    Serum samples were planned to be collected for the determination of anti-pembrolizumab antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps.



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:

  • Provide signed, written informed consent.
  • Male and female participants, age >=18 years (at the time consent is obtained).
  • Histological documentation of locally advanced, recurrent or metastatic solid malignancy that has progressed after standard therapy appropriate for the specific tumor type, or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate. Participants should not have received more than 5 prior lines of therapy for advanced disease including both standards of care and investigational therapies. Participants whose cancers harbor molecular alterations for which targeted therapy is standard of care should have received health authority approved appropriate targeted therapy for their tumor types before enrollment.
  • Participants with the following solid tumors are eligible for screening: Non-small cell lung cancer (NSCLC), Squamous cell carcinoma of the head and neck (SCCHN), Renal cell carcinoma (RCC), melanoma, bladder, Soft Tissue Sarcoma (STS), Triple-negative breast cancer (TNBC), and Colorectal carcinoma displaying high microsatellite instability (MSI CRC). In Part 2B (Cohort Expansion), specific subgroups of the above solid tumors will be studied. These subgroups may be defined by specific lines of treatment, types of prior treatment, histological subtypes, and may be enriched for selected biomarkers or participant characteristics. Populations to be studied in Amendment 3 include but are not limited to the following. Enrolment of additional populations will be communicated in writing: Participants with dedifferentiated liposarcoma who have not received prior treatment with a Programmed death ligand 1 (PD-L1) inhibitor; Participants with melanoma who have received a prior PD-L1 inhibitor, had a CR, PR or SD and subsequently progressed while on PD-L1 therapy. Participants who have received prior treatment with a PD-L1 inhibitor must have documented disease progression as defined by meeting all of the following criteria: Has received at least 2 doses of an approved PD-L1 inhibitor; has demonstrated disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. 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 PD , in the absence of rapid clinical progression; Progressive disease has been documented within 18 weeks from the last dose of the PD-L1 inhibitor.
  • In Parts 1A and 2A, a biopsy of the tumor tissue obtained at anytime from the initial diagnosis to study entry. Although a fresh biopsy obtained during screening is preferred, archival tumor specimen is acceptable if it is not feasible to obtain a fresh biopsy.

Participants enrolled in Part 1A or Part 2A Pharmacodynamic Cohorts or in Part 2B of the study must provide a fresh biopsy of a tumor lesion not previously irradiated during the screening period and must agree to provide at least one additional on-treatment biopsy. In addition, an archived tumor tissue should be submitted for Participants in Part 2B, if available. The criterion for collection of fresh biopsies may be waived once GlaxoSmithKline (GSK)has determined an appropriate number of viable tissue samples have been analyzed For Part 1B and Part 2B, any archival tumor specimen must have been obtained within 3 months of starting study drug.

  • Measurable disease as per RECIST v1.1
  • Palpable lesions that are not measurable by radiologic or photographic evaluations may not be utilized as the only measurable lesion.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
  • Life expectancy of at least 12 weeks.
  • Adequate organ function as defined by System Laboratory Values; Hematologic (Absolute neutrophil count [ANC] >=1.5x10^9/ liter [L], Lymphocyte count >=800/cubic millimeter [mm^3], Hemoglobin >=9 grams/deciliter [g/dL], Platelets >=100x10^9/L), Hepatic (Total bilirubin <=1.5x upper limit of normal [ULN] [For participants with Gilbert's Syndrome, only if direct bilirubin <=35 percent (%), <=3.0xULN], for Part 1A and 2A: alanine aminotransferase [ALT] <=1.5xULN), Part 2B: ALT <=2.5xULN; Renal (Serum Creatinine <=1.5xULN OR Calculated creatinine clearance [CrCl >50 mL/min ) and Endocrine (Thyroid stimulating hormone [TSH]) within normal limits. If TSH is not within normal limits at baseline, the participant may still be eligible if total triiodothyronine (T3) or free T3 and free thyroxine (T4) are within the normal limits.
  • QT duration corrected for heart rate by Fridericia's formula (QTcF) <450 milliseconds (msec) or <480 msec for participants with bundle branch block.
  • In France, a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
  • Female participant: is eligible to participate if she is not pregnant (as confirmed by a negative serum beta-human chorionic gonadotrophin [beta-hCG] test), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion ; Hysterectomy; Documented Bilateral Oophorectomy.

Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.

  • Reproductive potential and agrees to follow one of the options listed below in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until 120 days after the last dose of study medication and completion of the follow-up visit. GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP).

This list does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for participants who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis: Contraceptive subdermal implant with a <1% rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system with a <1% rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone; Injectable progestogen; Contraceptive vaginal ring; Percutaneous contraceptive patches; Male partner sterilization with documentation of azoospermia prior to the female participant's entry into the study, and this male is the sole partner for that participant. These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that participants understand how to properly use these methods of contraception.

  • Male Participants with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until 120 days after the last dose of study medication: Vasectomy with documentation of azoospermia; Male condom plus partner use of one of the contraceptive options below; Contraceptive subdermal implant with a <1% rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system with a <1% rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone Injectable progestogen; Contraceptive vaginal ring; Percutaneous contraceptive patches.

These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that participants understand how to properly use these methods of contraception.

Exclusion Criteria:

  • Prior treatment with the following agents (from last dose of prior treatment to first dose of GSK3174998): Tumor necrosis factor receptor (TNFR) agonists, including OX40, CD27, CD137 (4-1BB), CD357 (GITR): at any time; Checkpoint inhibitors, including Programmed death receptor-1 (PD-1),

    1, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors: within 4 weeks; other anticancer therapy, including chemotherapy, targeted therapy, and biological therapy: within 4 weeks or 5 half lives of the drug, whichever is shorter. Prior radiation therapy is permissible if at least one unirradiated measurable lesion is available for assessment via RECIST version 1.1. A wash out of at least two weeks before start of study drug for palliative radiation to the extremities for osseous bone metastases and 4 weeks for radiation to the chest, brain, or visceral organs is required; Investigational therapy: if the participant has participated in a clinical trial and has received an investigational product: within 30 days or 5 half-lives of the investigational product (whichever is shorter). At least 14 days must have passed between the last dose of prior investigational agent and the first dose of study drug.

  • Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.
  • Toxicity from previous treatment: Participants with >=Grade 3 toxicity related to prior immunotherapy leading to study treatment discontinuation are not eligible; participants whose toxicity related to prior treatment has not resolved to <=Grade 1 (except alopecia, hearing loss, grade <=2 neuropathy or endocrinopathy managed with replacement therapy) are not eligible.
  • Malignancy other than disease under study, except as noted below: any other malignancy from which the participant has been disease-free for more than 2 years and, in the opinion of the principal investigators and GSK Medical Monitor, will not affect the evaluation of the effects of this clinical trial treatment on currently targeted malignancy, can be included in this clinical trial.
  • Central nervous system (CNS) metastases, with the following exception: Participants who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids for 2 weeks prior to first dose of study drug.
  • Has 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 [GMCSF], recombinant erythropoietin) within 2 weeks before the first dose of study drug.
  • 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 2 years (that is with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (example [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 28 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.
  • Active infection, known human immunodeficiency virus infection, or positive test for hepatitis B surface antigen or hepatitis C.
  • 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).
  • Known, current drug or alcohol abuse.
  • Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction.
  • Receipt of any live vaccine within 4 weeks.
  • Recent history of allergen desensitization therapy within 4 weeks of starting study Treatment.
  • History of severe hypersensitivity to other mAbs.
  • History or evidence of cardiovascular risk including any of the following: Recent (within the past 6 months) history of serious uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities including second degree (Type II) or third degree atrioventricular block; Documented cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting, or bypass grafting within the past 6 months before enrollment; documented congestive heart failure (Class II, III, or IV) as defined by the New York Heart Association functional classification system; recent (within the past 6 months) history of symptomatic pericarditis Current or history of idiopathic pulmonary fibrosis, interstitial lung disease, or organizing pneumonia.
  • History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural effusions.
  • Any serious and/or unstable pre-existing medical, psychiatric disorder, or other condition that could interfere with the participant's safety, obtaining informed consent, or compliance to the study procedures.
  • Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective Institutional Review Board (IRB) approval (by chair or designee) is given allowing exception to this criterion for a specific participant.
  • History of severe hypersensitivity (>=Grade 3) to pembrolizumab and/or any of its excipients.

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): NCT02528357


Locations
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United States, Massachusetts
GSK Investigational Site
Boston, Massachusetts, United States, 02215
United States, New York
GSK Investigational Site
New York, New York, United States, 10016
GSK Investigational Site
New York, New York, United States, 10065
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37203
United States, Texas
GSK Investigational Site
Houston, Texas, United States, 77030
Canada, Ontario
GSK Investigational Site
Toronto, Ontario, Canada, M5G 2M9
France
GSK Investigational Site
Villejuif, France, 94805
Netherlands
GSK Investigational Site
Amsterdam, Netherlands, 1066 CX
Sponsors and Collaborators
GlaxoSmithKline
Merck Sharp & Dohme Corp.
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] February 4, 2020
Statistical Analysis Plan  [PDF] May 19, 2020

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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02528357    
Other Study ID Numbers: 201212
2015-000152-14 ( EudraCT Number )
First Posted: August 19, 2015    Key Record Dates
Results First Posted: May 18, 2021
Last Update Posted: May 18, 2021
Last Verified: April 2021
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, key secondary endpoints and safety data of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
GSK3174998
Non-small Cell Lung Cancer (NSCLC)
OX40
Pembrolizumab
Monoclonal Antibody (mAb)
Selected Advanced Solid Tumors
Additional relevant MeSH terms:
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Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents