Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase 1 First Time in Humans (FTIH), Open Label Study of GSK3745417 Administered to Subjects With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. 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: NCT03843359
Recruitment Status : Recruiting
First Posted : February 18, 2019
Last Update Posted : June 9, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This is a Phase I, FTIH, open-label, repeat-dose, non-randomized, multicenter, multi-country study to evaluate the safety, tolerability, and preliminary clinical activity and establish a recommended dose of GSK3745417 administered intravenously (IV) alone (Part 1) or co-administered (Part 2) with pembrolizumab in subjects with refractory/relapsed solid tumors. Each part consists of a dose escalation phase and a cohort expansion phase. In Part 1A, escalating doses of GSK3745417 will be evaluated as guided by the Neuenschwander-continuous reassessment method (N-CRM) approach. In Part 2A, escalating doses of GSK3745417 in combination with 200 milligrams (mg) pembrolizumab will be evaluated as guided by the N-CRM approach. In Part 1B and 2B, subjects will receive a single dose level of GSK3745417 as identified based on data from Part 1, either alone or in combination with pembrolizumab. A total of approximately 300 subjects will be enrolled in this study, approximately 120 for dose escalation cohorts, and approximately 180 in the expansion cohorts.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: GSK3745417 Drug: Pembrolizumab Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: In Part 1A, escalating doses of GSK3745417 will be evaluated as guided by the N-CRM approach. In Part 2A, escalating doses of GSK3745417 in combination with 200 mg pembrolizumab will be evaluated as guided by the N-CRM approach. In Part 1B and 2B, subjects will receive a single dose level of GSK3745417 as identified based on data from Part 1, either alone or in combination with 200 mg pembrolizumab.
Masking: None (Open Label)
Masking Description: This will be an Open-label study. Hence, there will no masking.
Primary Purpose: Treatment
Official Title: A Phase I First Time in Human Open Label Study of GSK3745417 Administered With and Without Anticancer Agents in Participants With Advanced Solid Tumors
Actual Study Start Date : March 12, 2019
Estimated Primary Completion Date : October 10, 2023
Estimated Study Completion Date : April 12, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1A: GSK3745417 Monotherapy, Dose-escalation Cohort
Subjects will receive GSK3745417 IV at every one week intervals (Q1W). Escalating doses of GSK3745417 will be evaluated using NCRM approach.
Drug: GSK3745417
GSK3745417 is available as white to off-white cake or powder for solution for injection at a unit dose strength of 2 mg per vial. GSK3745417 will be administered as IV injection for up to 5 minutes.

Experimental: Part 1B: GSK3745417 Monotherapy Dose Expansion Cohort
Subjects will be administered the recommended Phase 2 dose of GSK3745417 IV Q1W established in Part 1A of the study.
Drug: GSK3745417
GSK3745417 is available as white to off-white cake or powder for solution for injection at a unit dose strength of 2 mg per vial. GSK3745417 will be administered as IV injection for up to 5 minutes.

Experimental: Part 2A: GSK3745417 + pembrolizumab, Dose escalation Cohort
Subjects will receive GSK3745417 IV Q1W for 2 weeks followed by GSK3745417 along with pembrolizumab 200 mg IV once every 3 weeks (Q3W). Escalating doses of GSK3745417 in combination with 200 mg pembrolizumab will be evaluated.
Drug: GSK3745417
GSK3745417 is available as white to off-white cake or powder for solution for injection at a unit dose strength of 2 mg per vial. GSK3745417 will be administered as IV injection for up to 5 minutes.

Drug: Pembrolizumab
Pembrolizumab is available as solution for infusion or lyophilized powder for reconstitution to be administered at a dose of 200 mg Q3W. It will be administered as an IV infusion for 30 minutes.

Experimental: Part 2B: GSK3745417 combination Expansion Cohort
Subjects will receive GSK3745417 IV Q1W for 2 weeks then once every 3 week (Q3W) in combination with pembrolizumab 200 mg IV Q3W.
Drug: GSK3745417
GSK3745417 is available as white to off-white cake or powder for solution for injection at a unit dose strength of 2 mg per vial. GSK3745417 will be administered as IV injection for up to 5 minutes.

Drug: Pembrolizumab
Pembrolizumab is available as solution for infusion or lyophilized powder for reconstitution to be administered at a dose of 200 mg Q3W. It will be administered as an IV infusion for 30 minutes.




Primary Outcome Measures :
  1. 1A: Number of subjects achieving Dose-limiting toxicity (DLT) [ Time Frame: Up to Day 21 ]
    DLT is defined as any Grade 3 or 4 cytokine release syndrome; alanine aminotransferase (ALT) >=3 times upper limit of normal (ULN),plus bilirubin >=2 times ULN (>35% direct) or plus international normalized ratio (INR)>1.5 (possible Hy's law);or both ALT >=5 times ULN and >=2 times Baseline value (in subjects with liver metastases/tumor infiltration at Baseline);Grade >=3 non-hematologic toxicity of any duration with exceptions: Transient (<=72 hours) abnormal laboratory value without associated clinically significant signs or symptoms; Nausea, vomiting, or diarrhea adequately controlled with supportive care within 48 hours;Alopecia; Grade >=3 fatigue in subjects with Baseline fatigue of grade <=2. Grade >=3 immune related toxicity;any other event which in judgment of investigator and GlaxoSmithKline Medical Monitor is considered to be a DLT;Grade 4 anemia;Grade 4 neutropenia of >7 days duration or febrile neutropenia;Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding.

  2. 1A: Number of subjects with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 2 years ]
    An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or requires medical judgement.

  3. 1A: Severity of AEs [ Time Frame: Up to 2 years ]
    The severity of AEs will be graded utilizing the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.

  4. 2A: Number of subjects achieving DLT [ Time Frame: Up to Day 29 ]
    DLT is defined as any Grade 3 or 4 cytokine release syndrome; ALT >=3 times ULN,plus bilirubin >=2 times ULN (>35% direct) or plus INR>1.5 (possible Hy's law);or both ALT >=5 times ULN and >=2 times Baseline value (in subjects with liver metastases/tumor infiltration at Baseline);Grade >=3 non-hematologic toxicity of any duration with exceptions: Transient (<=72 hours) abnormal laboratory value without associated clinically significant signs or symptoms; Nausea, vomiting, or diarrhea adequately controlled with supportive care within 48 hours;Alopecia; Grade >=3 fatigue in subjects with Baseline fatigue of grade <=2. Grade >=3 immune related toxicity;any other event which in judgment of investigator and GlaxoSmithKline Medical Monitor is considered to be a DLT;Grade 4 anemia;Grade 4 neutropenia of >7 days duration or febrile neutropenia;Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding.

  5. 2A: Number of subjects with AEs and SAEs [ Time Frame: Up to 2 years ]
    An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or requires medical judgement.

  6. 2A: Severity of AEs [ Time Frame: Up to 2 years ]
    The severity of AEs will be graded utilizing the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.

  7. 1B: Objective response rate based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria [ Time Frame: Up to 2 years ]
    Objective response rate is defined as the percentage of subjects with a best overall confirmed complete response (CR) or partial response (PR) at any time as per disease-specific criteria.

  8. 2B: Objective response rate based on RECIST 1.1 criteria [ Time Frame: Up to 2 years ]
    Objective response rate is defined as the percentage of subjects with a best overall confirmed CR or PR at any time as per disease-specific criteria.


Secondary Outcome Measures :
  1. 1A: Best objective response based on RECIST 1.1 criteria [ Time Frame: Up to 2 years ]
    Best objective response rate is defined as the percentage of subjects with a best overall confirmed CR or PR at any time as per disease-specific criteria.

  2. 1A: GSK3745417 concentrations in plasma following administration of GSK3745417 alone [ Time Frame: Pre-dose, 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-injection at Weeks 1, 2, 3, 4, 5, 6, 9 and 12 ]
    Blood samples will be collected at indicated time points for plasma pharmacokinetic (PK) analysis of GSK3745417.

  3. 1A: Maximum observed concentration (Cmax) following administration of GSK3745417 alone [ Time Frame: Pre-dose, 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-injection at Weeks 1, 2, 3, 4, 5, 6, 9 and 12 ]
    Blood samples will be collected at indicated time points for plasma PK analysis following administration of GSK3745417 monotherapy.

  4. 1A: Area under the concentration-time curve (AUC) following administration of GSK3745417 alone [ Time Frame: Pre-dose, 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-injection at Weeks 1, 2, 3, 4, 5, 6, 9 and 12 ]
    Blood samples will be collected at indicated time points for plasma PK analysis following administration of GSK3745417 monotherapy.

  5. 1A: Apparent terminal phase half-life (t½) following administration of GSK3745417 alone [ Time Frame: Pre-dose, 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-injection at Weeks 1, 2, 3, 4, 5, 6, 9 and 12 ]
    Blood samples will be collected at indicated time points for plasma PK analysis following administration of GSK3745417 monotherapy.

  6. 2A: Best objective response based on RECIST 1.1 criteria [ Time Frame: Up to 2 years ]
    Best objective response rate is defined as the percentage of subjects with a best overall confirmed CR or PR at any time as per disease-specific criteria.

  7. 2A: GSK3745417 concentrations in plasma following administration of GSK3745417 in combination with pembrolizumab [ Time Frame: Pre-dose, 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post injection at Weeks 1, 2, 5, 8, 11, 14 and 17 ]
    Blood samples will be collected for plasma PK analysis of GSK3745417 following administration of GSK3745417 in combination with pembrolizumab.

  8. 2A: Cmax following administration of GSK3745417 in combination with pembrolizumab [ Time Frame: Pre-dose, 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post injection at Weeks 1, 2, 5, 8, 11, 14 and 17 ]
    Blood samples will be collected at indicated time points for plasma PK analysis following administration of GSK3745417 in combination with pembrolizumab.

  9. 2A: AUC following administration of GSK3745417 in combination with pembrolizumab [ Time Frame: Pre-dose, 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post injection at Weeks 1, 2, 5, 8, 11, 14 and 17 ]
    Blood samples will be collected at indicated time points for plasma PK analysis following administration of GSK3745417 in combination with pembrolizumab.

  10. 2A: t½ following administration of GSK3745417 in combination with pembrolizumab [ Time Frame: Pre-dose, 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post injection at Weeks 1, 2, 5, 8, 11, 14 and 17 ]
    Blood samples will be collected at indicated time points for plasma PK analysis following administration of GSK3745417 in combination with pembrolizumab.

  11. 1B: Number of subjects achieving DLT [ Time Frame: Up to Day 21 ]
    DLT is defined as any Grade 3 or 4 cytokine release syndrome; ALT >=3 times ULN,plus bilirubin >=2 times ULN (>35% direct) or plus INR>1.5 (possible Hy's law);or both ALT >=5 times ULN and >=2 times Baseline value (in subjects with liver metastases/tumor infiltration at Baseline);Grade >=3 non-hematologic toxicity of any duration with exceptions: Transient (<=72 hours) abnormal laboratory value without associated clinically significant signs or symptoms; Nausea, vomiting, or diarrhea adequately controlled with supportive care within 48 hours;Alopecia; Grade >=3 fatigue in subjects with Baseline fatigue of grade <=2. Grade >=3 immune related toxicity;any other event which in judgment of investigator and GlaxoSmithKline Medical Monitor is considered to be a DLT;Grade 4 anemia;Grade 4 neutropenia of >7 days duration or febrile neutropenia;Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding.

  12. 1B: Number of subjects with AEs and SAEs [ Time Frame: Up to 2 years ]
    An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or requires medical judgement.

  13. 1B: Severity of AEs [ Time Frame: Up to 2 years ]
    The severity of AEs will be graded utilizing the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.

  14. 1B: GSK3745417 concentrations in plasma following administration of GSK3745417 alone [ Time Frame: Pre-dose, 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-injection at Weeks 1, 2, 3, 4, 5, 6, 9 and 12 ]
    Blood samples will be collected at indicated time points for plasma PK analysis of GSK3745417.

  15. 1B: Cmax following administration of GSK3745417 alone [ Time Frame: Pre-dose, 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-injection at Weeks 1, 2, 3, 4, 5, 6, 9 and 12 ]
    Blood samples will be collected at indicated time points for plasma PK analysis following administration of GSK3745417 alone.

  16. 1B: AUC following administration of GSK3745417 alone [ Time Frame: Pre-dose, 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-injection at Weeks 1, 2, 3, 4, 5, 6, 9 and 12 ]
    Blood samples will be collected at indicated time points for plasma PK analysis following administration of GSK3745417 alone.

  17. 1B: t½ following administration of GSK3745417 alone [ Time Frame: Pre-dose, 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-injection at Weeks 1, 2, 3, 4, 5, 6, 9 and 12 ]
    Blood samples will be collected at indicated time points for plasma PK analysis following administration of GSK3745417 alone.

  18. 2B: Number of subjects achieving DLT [ Time Frame: Up to Day 29 ]
    DLT is defined as any Grade 3 or 4 cytokine release syndrome; ALT >=3 times ULN,plus bilirubin >=2 times ULN (>35% direct) or plus INR>1.5 (possible Hy's law);or both ALT >=5 times ULN and >=2 times Baseline value (in subjects with liver metastases/tumor infiltration at Baseline);Grade >=3 non-hematologic toxicity of any duration with exceptions: Transient (<=72 hours) abnormal laboratory value without associated clinically significant signs or symptoms; Nausea, vomiting, or diarrhea adequately controlled with supportive care within 48 hours;Alopecia; Grade >=3 fatigue in subjects with Baseline fatigue of grade <=2. Grade >=3 immune related toxicity;any other event which in judgment of investigator and GlaxoSmithKline Medical Monitor is considered to be a DLT;Grade 4 anemia;Grade 4 neutropenia of >7 days duration or febrile neutropenia;Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding.

  19. 2B: 2B: Number of subjects with AEs and SAEs [ Time Frame: Up to 2 years ]
    An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or requires medical judgement.

  20. 2B: Severity of AEs [ Time Frame: Up to 2 years ]
    The severity of AEs will be graded utilizing the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.

  21. 2B: GSK3745417 concentrations in plasma following administration of GSK3745417 in combination with pembrolizumab [ Time Frame: Pre-dose, 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post injection at Weeks 1, 2, 5, 8, 11, 14 and 17 ]
    Blood samples will be collected at indicated time points for plasma PK analysis of GSK3745417.

  22. 2B: Cmax following administration of GSK3745417 in combination with pembrolizumab [ Time Frame: Pre-dose, 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post injection at Weeks 1, 2, 5, 8, 11, 14 and 17 ]
    Blood samples will be collected at indicated time points for plasma PK analysis following administration of GSK3745417 in combination with pembrolizumab.

  23. 2B: AUC following administration of GSK3745417 in combination with pembrolizumab [ Time Frame: Pre-dose, 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post injection at Weeks 1, 2, 5, 8, 11, 14 and 17 ]
    Blood samples will be collected at indicated time points for plasma PK analysis following administration of GSK3745417 in combination with pembrolizumab.

  24. 2B: t½ following administration of GSK3745417 in combination with pembrolizumab [ Time Frame: Pre-dose, 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post injection at Weeks 1, 2, 5, 8, 11, 14 and 17 ]
    Blood samples will be collected at indicated time points for plasma PK analysis following administration of GSK3745417 in combination with pembrolizumab.



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.


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

Inclusion Criteria

  • Subject must be >=18 years of age at the time of signing the informed consent.
  • Subjects with advanced/recurrent solid tumors, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established.
  • Histological or cytological documentation of an advanced solid tumor.
  • A biopsy of the tumor tissue obtained at any time from the initial diagnosis to study entry. Although a fresh biopsy obtained during screening is preferred, archival tumor specimen is acceptable if it is not feasible to obtain a fresh biopsy. Subjects enrolled in the PK/Pharmacodynamic Cohorts 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.
  • Measurable disease per RECIST version 1.1. Palpable lesions that are measurable by radiologic or photographic evaluations may be utilized as the only measurable lesion.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
  • Life expectancy of at least 12 weeks.
  • In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
  • Adequate organ function (hematologic system: Absolute neutrophil count [ANC] >=1.5x10^9/Liter, Hemoglobin >=9 grams per deciliter [g/dL], Platelets >=100x10^9/Liter, prothrombin time [PT]/ INR and partial thromboplastin time [PTT] [unless subject is receiving anticoagulant] <1.5 times ULN; Hepatic system: Total bilirubin <=1.5 times ULN and for subjects with Gilbert's Syndrome [only if direct bilirubin <=35%] total bilirubin <=3.0 times ULN; ALT <=2.5 times ULN, for subjects with liver metastases/tumor infiltration <=5 times ULN; renal system: Estimated glomerular filtration rate [eGFR] by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] >60 milliliter per minute [mL/min]; Endocrine system: thyroid stimulating hormone (TSH) within normal limits; Cardiac system: Ejection fraction >= 50% by echocardiogram.
  • Male or female: Female subjects are eligible to participate if they are not either pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, during the study treatment period and for at least 7 days (subjects receiving monotherapy) or 120 days (subjects receiving pembrolizumab) after the last dose of study treatment and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) as required by local regulations) within 7 days before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the subject must be excluded from participation if the serum pregnancy result is positive. Additional requirements for pregnancy testing during and after study treatment. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
  • Capable of giving signed informed consent.

Exclusion Criteria

  • Malignancy other than disease under study with the exception of those from which the subject has been disease-free for more than 2 years and not expected to affect the safety of the subject or the endpoints of the trial. Curatively treated non-melanoma skin cancer is permitted.
  • Symptomatic central nervous system (CNS) metastases or asymptomatic CNS metastases that have required steroids within 2 weeks prior to first dose of study treatment. Subjects with carcinomatous meningitis or leptomeningeal spread are excluded regardless of clinical stability.
  • Active autoimmune disease that has required systemic disease modifying or immunosuppressive treatment within the last 2 years. Replacement therapy (e.g., thyroxine or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is permitted.
  • Concurrent medical condition requiring the use of systemic immunosuppressive treatment 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 subject is on a stable dose.
  • Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if subject otherwise meets entry criteria.
  • History of vasculitis at any time prior to study treatment.
  • Evidence or history of significant active bleeding or coagulation disorder.
  • Active infection requiring systemic treatment, known human immunodeficiency virus infection, or positive test for hepatitis B surface antigen or hepatitis C.
  • QTcF >450 milliseconds (msec) or QTcF >480 msec for subjects with bundle branch block. QTcF is the QT interval corrected for heart rate according to Fridericia's formula, machine-read or manually over-read.
  • Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction.
  • Recent history of allergen desensitization therapy within 4 weeks of starting study treatment.
  • History or evidence of cardiovascular (CV) 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; Cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting, or bypass grafting within the past 6 months before enrolment; Congestive heart failure (Class II, III, or IV) as defined by the New York Heart Association functional classification system (NYHA).
  • Recent (within the past 6 months) history of symptomatic pericarditis.
  • History of idiopathic pulmonary fibrosis, interstitial lung disease, or organizing pneumonia, or evidence of active, non-infectious pneumonitis. 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 Sponsor.
  • 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 subject'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 subject.
  • Prior treatment with the following agents: Stimulator of Interferon Genes (STING) agonist at any time. Subjects treated in Part 1/monotherapy with GSK3745417 may be enrolled into Part 2/combination with pembrolizumab upon disease progression and upon discussion and approval from the GSK Medical Monitor; Anticancer therapy or investigational therapy within 28 days or 5 half-lives of the drug, whichever is shorter; Checkpoint inhibitors, including Programmed death receptor-1 (PD-1), PD-L1 and Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors within 28 days; Prior radiation therapy: permissible if at least 1 non-irradiated measurable lesion is available for assessment according to RECIST version 1.1 or if a solitary measurable lesion was irradiated, objective progression is documented. A wash out of at least 28 days before start of study treatment for radiation of any intended use to the extremities for bone metastases and 28 days for radiation to the chest, brain, or visceral organs is required. Palliative radiation is permissible at any time before or during the study.
  • Receipt of any live vaccine within 30 days of the start of study treatment.
  • Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.
  • Toxicity from previous treatment including: Toxicity Grade >=3 related to prior immunotherapy and that led to study treatment discontinuation; Toxicity related to prior treatment that has not resolved to Grade <=1 (except alopecia, hearing loss or grade <=2 neuropathy or endocrinopathy managed with replacement therapy).
  • Received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, and recombinant erythropoietin) within 14 days before the first dose of study treatment.
  • Concomitant administration of drugs that are sensitive substrates or narrow therapeutic range substrates for cytochrome p450 (CYP) 3A4, 1A2, 2C19 enzymes and OATP1B1 transporter, and moderate to strong inducers and inhibitors of CYP 3A4 should be excluded during the study and for 7 days prior to and following treatment with GSK3745417 (14 days for itraconazole).
  • Major surgery <=28 days before the first dose of study treatment. Subjects must have also fully recovered from any surgery (major or minor) and/or its complications before initiating study treatment.
  • Known drug or alcohol abuse.

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): NCT03843359


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
Layout table for location information
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         
United States, Texas
GSK Investigational Site Recruiting
Houston, Texas, United States, 77030
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: Funda Meric-Bernstam         
Australia, Victoria
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: Jayesh Desai         
Canada, Ontario
GSK Investigational Site Recruiting
Toronto, Ontario, Canada, M5G 1Z9
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: Philippe Bedard         
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         
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
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         
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03843359    
Other Study ID Numbers: 208850
First Posted: February 18, 2019    Key Record Dates
Last Update Posted: June 9, 2020
Last Verified: June 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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
GSK3745417, pembrolizumab, solid tumor, first time in human, Stimulator of Interferon Genes, STING
Additional relevant MeSH terms:
Layout table for MeSH terms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents