Clinical Trials /

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

NCT03447314

Description:

GSK1795091 is being developed for administration in combination with other immune system modulators for the treatment of cancers. The study will be conducted in two parts. In Part 1, dose escalation will be performed to identify combination dose levels comprising GSK1795091 with either 24 milligrams (mg) GSK3174998 (Part 1a), 80 mg GSK3359609 (Part 1b), or 200 mg pembrolizumab (Part 1c). One dose level of GSK3174998, GSK3359609, or pembrolizumab with up to 5 dose levels of GSK1795091 are planned for evaluation. In Part 2 (dose-expansion), subjects will receive a single dose level of GSK1795091 as identified based on data from Part 1, in combination with either GSK3174998, GSK3359609, or pembrolizumab.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of a Combination of GSK1795091 and Immunotherapies in Subjects With Advanced Solid Tumors
  • Official Title: A Phase I, Open-Label Study of GSK1795091 Administered in Combination With Immunotherapies in Participants With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 204686
  • SECONDARY ID: 2017-003545-23
  • NCT ID: NCT03447314

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
GSK1795091Part 1a: 100ng GSK1795091 + 24mg GSK3174998
GSK3174998Part 1a: 100ng GSK1795091 + 24mg GSK3174998
GSK3359609Part 1b: 100ng GSK1795091 + 80mg GSK3359609
PembrolizumabPart 1b: 100ng GSK1795091 + 80mg GSK3359609

Purpose

GSK1795091 is being developed for administration in combination with other immune system modulators for the treatment of cancers. The study will be conducted in two parts. In Part 1, dose escalation will be performed to identify combination dose levels comprising GSK1795091 with either 24 milligrams (mg) GSK3174998 (Part 1a), 80 mg GSK3359609 (Part 1b), or 200 mg pembrolizumab (Part 1c). One dose level of GSK3174998, GSK3359609, or pembrolizumab with up to 5 dose levels of GSK1795091 are planned for evaluation. In Part 2 (dose-expansion), subjects will receive a single dose level of GSK1795091 as identified based on data from Part 1, in combination with either GSK3174998, GSK3359609, or pembrolizumab.

Trial Arms

NameTypeDescriptionInterventions
Part 1a: 50ng GSK1795091 + 24mg GSK3174998ExperimentalParticipants will be administered GSK1795091 50 nanogram (ng) intravenously (IV) on Days 1 and 8 followed by once weekly administration of GSK1795091 50 ng IV in combination with GSK3174998 24 milligram (mg) administered at 3-week intervals (Q3W) via the IV route until Week 12. From Week 12 onwards, GSK1795091 50 ng IV will be administered in combination with GSK3174998 24 mg at Q3W interval.
  • GSK1795091
  • GSK3174998
Part 1a: 100ng GSK1795091 + 24mg GSK3174998ExperimentalParticipants will be administered GSK1795091 100 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 100 ng IV in combination with GSK3174998 24 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 100 ng IV will be administered in combination with GSK3174998 24 mg at Q3W interval.
  • GSK1795091
  • GSK3174998
Part 1a: 150ng GSK1795091 + 24mg GSK3174998ExperimentalParticipants will be administered GSK1795091 150 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 150 ng IV in combination with GSK3174998 24 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 150 ng IV will be administered in combination with GSK3174998 24 mg at Q3W interval.
  • GSK1795091
  • GSK3174998
Part 1a: 200ng GSK1795091 + 24mg GSK3174998ExperimentalParticipants will be administered GSK1795091 200 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 200 ng IV in combination with GSK3174998 24 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 200 ng IV will be administered in combination with GSK3174998 24 mg at Q3W interval.
  • GSK1795091
  • GSK3174998
Part 1a: 250ng GSK1795091 + 24mg GSK3174998ExperimentalParticipants will be administered GSK1795091 250 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 250 ng IV in combination with GSK3174998 24 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 250 ng IV will be administered in combination with GSK3174998 24 mg at Q3W interval.
  • GSK1795091
  • GSK3174998
Part 1b: 50ng GSK1795091 + 80mg GSK3359609ExperimentalParticipants will be administered GSK1795091 50 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 50 ng IV in combination with GSK3359609 80 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 50 ng IV will be administered in combination with GSK3359609 80 mg at Q3W interval.
  • GSK1795091
  • GSK3359609
Part 1b: 100ng GSK1795091 + 80mg GSK3359609ExperimentalParticipants will be administered GSK1795091 100 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 100 ng IV in combination with GSK3359609 80 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 100 ng IV will be administered in combination with GSK3359609 80 mg at Q3W interval.
  • GSK1795091
  • GSK3359609
  • Pembrolizumab
Part 1b: 150ng GSK1795091 + 80mg GSK3359609ExperimentalParticipants will be administered GSK1795091 150 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 150 ng IV in combination with GSK3359609 80 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 150 ng IV will be administered in combination with GSK3359609 80 mg at Q3W interval.
  • GSK1795091
  • GSK3359609
Part 1b: 200ng GSK1795091 + 80mg GSK3359609ExperimentalParticipants will be administered GSK1795091 200 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 200 ng IV in combination with GSK3359609 80 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 200 ng IV will be administered in combination with GSK3359609 80 mg at Q3W interval.
  • GSK1795091
  • GSK3359609
Part 1b: 250ng GSK1795091 + 80mg GSK3359609ExperimentalParticipants will be administered GSK1795091 250 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 250 ng IV in combination with GSK3359609 80 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 250 ng IV will be administered in combination with GSK3359609 80 mg at Q3W interval.
  • GSK1795091
  • GSK3359609
Part 1c: 50ng GSK1795091 + 200mg PembrolizumabExperimentalParticipants will be administered GSK1795091 50 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 50 ng IV in combination with pembrolizumab 200 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 50 ng IV will be administered in combination with pembrolizumab 200 mg at Q3W interval.
  • GSK1795091
  • Pembrolizumab
Part 1c: 100ng GSK1795091 + 200mg PembrolizumabExperimentalParticipants will be administered GSK1795091 100 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 100 ng IV in combination with pembrolizumab 200 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 100 ng IV will be administered in combination with pembrolizumab 200 mg at Q3W interval.
  • GSK1795091
  • Pembrolizumab
Part 1c: 150ng GSK1795091 + 200mg PembrolizumabExperimentalParticipants will be administered GSK1795091 150 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 150 ng IV in combination with pembrolizumab 200 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 150 ng IV will be administered in combination with pembrolizumab 200 mg at Q3W interval.
  • GSK1795091
  • Pembrolizumab
Part 1c: 200ng GSK1795091 + 200mg PembrolizumabExperimentalParticipants will be administered GSK1795091 200 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 200 ng IV in combination with pembrolizumab 200 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 200 ng IV will be administered in combination with pembrolizumab 200 mg at Q3W interval.
  • GSK1795091
  • Pembrolizumab
Part 1c: 250ng GSK1795091 + 200mg PembrolizumabExperimentalParticipants will be administered GSK1795091 250 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 250 ng IV in combination with pembrolizumab 200 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 250 ng IV will be administered in combination with pembrolizumab 200 mg at Q3W interval.
  • GSK1795091
  • Pembrolizumab
Part 2a: GSK1795091 + 24 mg GSK3174998ExperimentalParticipants will be administered GSK1795091 at a dose identified in Part 1 along with GSK3174998 24 mg.
  • GSK1795091
  • GSK3174998
Part 2b: GSK1795091 + 80 mg GSK3359609ExperimentalParticipants will be administered GSK1795091 at a dose identified in Part 1 along with GSK3359609 80 mg.
  • GSK1795091
  • GSK3359609
Part 2c: GSK1795091 + 200 mg PembrolizumabExperimentalParticipants will be administered GSK1795091 at a dose identified in Part 1 along with pembrolizumab 200 mg.
  • GSK1795091
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Subject must be >=18 years of at the time of signing the informed consent.

          -  Histological documentation of advanced solid tumor.

          -  Archival tumor tissue obtained at any time from the initial diagnosis to study entry.
             Although a fresh biopsy obtained during screening is preferred, archival tumor
             specimen is acceptable if it is not feasible to obtain a fresh biopsy. Subjects
             enrolled in a PK/Pharmacodynamic Cohort must provide a fresh biopsy of a tumor lesion
             not previously irradiated during the screening period and must agree to provide at
             least one additional on-treatment biopsy.

          -  Disease that has progressed after standard therapies or for which standard therapy is
             otherwise unsuitable (example, intolerance).

          -  Measurable disease, that is, presenting with at least 1 measurable lesion per Response
             Evaluation Criteria in Solid Tumors (RECIST version 1.1).

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

          -  Life expectancy of at least 12 weeks.

          -  Adequate organ function.

          -  In France, a subject will be eligible for inclusion in this study only if either
             affiliated to or a beneficiary of a social security category.

          -  Male or female subjects will be included. A female subject is eligible to participate
             if she is not pregnant, not breastfeeding, and at least 1 of the following conditions
             applies: a) Not a woman of childbearing potential (WOCBP) OR b). A WOCBP who agrees to
             follow the contraceptive guidance during the treatment period and for at least 120
             days after the last dose of study treatment.

          -  Capable of giving signed informed consent which includes compliance with the
             requirements and restrictions specified.

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

          -  Histological or cytological documentation of squamous cell carcinoma of the head and
             neck (SCCHN) (oral cavity, oropharynx, hypopharynx, or larynx) that is recurrent,
             locally advanced, or metastatic and is not amenable to curative treatment options,
             surgery or definitive chemoradiation therapy.

          -  Received, ineligible for, or otherwise unsuitable for platinum-based therapy and
             anti-Programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy

          -  Received no more than 3 prior lines of systemic therapy for metastatic disease.

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

          -  Histological or cytological documentation of SCCHN (oral cavity, oropharynx,
             hypopharynx, or larynx) that is recurrent, locally advanced, or metastatic and is not
             amenable to curative treatment options, surgery or definitive chemoradiation therapy.

          -  Received no more than 2 prior lines of systemic therapy for metastatic disease.

        Exclusion Criteria:

          -  Malignancy other than disease under study with the exception of those from which the
             subject has been disease-free for more than 2 years and not expected to affect the
             safety of the subject or the endpoints of the trial.

          -  Symptomatic central nervous system (CNS) metastases or asymptomatic CNS metastases
             that have required steroids within 2 weeks prior to first dose of study treatment.

          -  Active autoimmune disease that has required systemic disease modifying or
             immunosuppressive treatment within the last 2 years. Replacement therapy (example,
             thyroxine or physiologic corticosteroid replacement therapy for adrenal or pituitary
             insufficiency) is permitted.

          -  Concurrent medical condition requiring the use of systemic immunosuppressive treatment
             within 28 days before the first dose of study treatment.

          -  Known human immunodeficiency virus infection.

          -  Current unstable liver or biliary disease per investigator assessment defined by the
             presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or
             gastric varices, persistent jaundice, or cirrhosis.

          -  Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior
             to first dose of study treatment.

          -  Positive Hepatitis C test result at screening or within 3 months prior to first dose
             of study treatment.

          -  QT interval corrected for heart rate according to Fridericia's formula (QTcF) >450
             milliseconds (msec) or QTcF >480 msec for subjects with bundle branch block

          -  Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel
             disease, intra-abdominal abscess, or gastrointestinal obstruction.

          -  Recent history of allergen desensitization therapy within 4 weeks of starting study
             treatment.

          -  History of severe hypersensitivity to monoclonal antibodies (mAbs).

          -  History or evidence of cardiovascular (CV) risk including any of the following: a)
             Recent (within the past 6 months) history of serious uncontrolled cardiac arrhythmia
             or clinically significant ECG abnormalities including second degree (Type II) or third
             degree atrioventricular block. b) Cardiomyopathy, myocardial infarction, acute
             coronary syndromes (including unstable angina pectoris), coronary angioplasty,
             stenting, or bypass grafting within the past 6 months before enrollment. c) Congestive
             heart failure (Class II, III, or IV) as defined by the New York Heart Association
             (NYHA) functional classification system. d) Recent (within the past 6 months) history
             of symptomatic pericarditis.

          -  History of idiopathic pulmonary fibrosis, pneumonitis, interstitial lung disease, or
             organizing pneumonia, or evidence of active, non-infectious pneumonitis.

          -  Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural
             effusions.

          -  Any serious and/or unstable pre-existing medical, psychiatric disorder, or other
             condition that could interfere with the subject's safety, obtaining informed consent,
             or compliance to the study procedures.

          -  Is or has an immediate family member (example, spouse, parent/legal guardian, sibling
             or child) who is investigational site or sponsor staff directly involved with this
             trial, unless prospective Institutional Review Board (IRB) approval (by chair or
             designee) is given allowing exception to this criterion for a specific subject.

          -  Prior treatment with the following agents: a) OX40, inducible T-cell co-stimulator
             (ICOS) agonist at any time. b) Prior systemic or intratumoral therapy with TLR
             agonist. c) Anticancer therapy or investigational therapy within 30 days or 5
             half-lives of the drug, whichever is shorter. d) Prior radiation therapy: permissible
             if at least 1 non-irradiated measurable lesion is available for assessment according
             to RECIST version 1.1 or if a solitary measurable lesion was irradiated, objective
             progression is documented. A wash out of at least 14 days before start of study
             treatment for radiation of any intended use to the extremities for bone metastases and
             28 days for radiation to the chest, brain, or visceral organs is required.

          -  Prior allogeneic or autologous bone marrow transplantation or other solid organ
             transplantation.

          -  Toxicity from previous treatment including: a) Toxicity Grade >=3 related to prior
             immunotherapy and that lead to study treatment discontinuation. b) Toxicity related to
             prior treatment has not resolved to Grade <=1 (except alopecia, or endocrinopathy
             managed with replacement therapy).

          -  Received transfusion of blood products (including platelets or red blood cells) or
             administration of colony stimulating factors (including granulocyte colony-stimulating
             factor [G-CSF], granulocyte macrophage colony-stimulating factor, and recombinant
             erythropoietin) within 2 weeks before the first dose of study treatment.

          -  Major surgery <=4 weeks before the first dose of study treatment. Subjects must have
             also fully recovered from any surgery (major or minor) and/or its complications before
             initiating study treatment.

          -  Known drug or alcohol abuse.

          -  Receipt of any live vaccine within 4 weeks.

        Additional Exclusion Criteria for Subjects in Part 2c

          -  Received prior anti-PD-1/PD-L1 therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs (STEAEs)
Time Frame:Up to 27 months
Safety Issue:
Description:An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A serious adverse event is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement or associated with liver injury and impaired liver function. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication. All Treated Population consisted of all participants who received at least 1 dose of GSK1795091, GSK3174998, GSK3359609, or pembrolizumab.

Secondary Outcome Measures

Measure:Part 1: Objective Response Rate
Time Frame:Up to 2 years
Safety Issue:
Description:Objective response rate is defined as the percentage of participants achieving a confirmed best overall response of complete response (CR) or partial response (PR) evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1, where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeters (mm) in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Measure:Part 2: Objective Response Rate
Time Frame:Up to 2 years
Safety Issue:
Description:Objective response rate is defined as the percentage of participants achieving a confirmed best overall response of CR or PR evaluated using RECIST v 1.1, where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Measure:Part 1: Disease Control Rate
Time Frame:Up to 2 years
Safety Issue:
Description:Disease control rate is defined as the percentage of participants with a confirmed best overall response of CR or PR or at least 12 weeks of stable disease per RECIST v 1.1.
Measure:Part 2: Disease Control Rate
Time Frame:Up to 2 years
Safety Issue:
Description:Disease control rate is defined as the percentage of participants with a confirmed best overall response of CR or PR or at least 12 weeks of stable disease per RECIST v 1.1.
Measure:Part 1: Time to Response
Time Frame:Up to 2 years
Safety Issue:
Description:Time to response is defined as the time from the date of first dose to the date of the first documented evidence of response (PR or CR).
Measure:Part 2: Time to Response
Time Frame:Up to 2 years
Safety Issue:
Description:Time to response is defined as the time from the date of first dose to the date of the first documented evidence of response (PR or CR).
Measure:Part 1: Duration of Response
Time Frame:Up to 2 years
Safety Issue:
Description:Duration of response is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause among participants who achieve an overall response (that is., a confirmed best overall response of CR or PR) by RECIST v 1.1.
Measure:Part 2: Duration of Response
Time Frame:Up to 2 years
Safety Issue:
Description:Duration of response is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause among participants who achieve an overall response (that is., a confirmed best overall response of CR or PR) by RECIST v 1.1.
Measure:Part 1: Progression-free Survival
Time Frame:Up to 2 years
Safety Issue:
Description:Progression-free survival is defined as the interval of time (in months) between the date of first dose to the date of disease progression according to clinical or radiological assessment or death due to any causes, whichever occurs earliest. PFS was determined according to RECIST version 1.1. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
Measure:Part 2: Progression-free Survival
Time Frame:Up to 2 years
Safety Issue:
Description:Progression-free survival is defined as the interval of time (in months) between the date of first dose to the date of disease progression according to clinical or radiological assessment or death due to any causes, whichever occurs earliest by RECIST v 1.1. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
Measure:Part 1: Overall Survival
Time Frame:Up to 27 months
Safety Issue:
Description:Overall survival is defined as time from the date of first dose of study treatment (whichever investigational drug administered first) to the date of death due to any cause.
Measure:Part 2: Overall Survival
Time Frame:Up to 27 months
Safety Issue:
Description:Overall survival is defined as time from the date of first dose of study treatment (whichever investigational drug administered first) to the date of death due to any cause.
Measure:Part 1a: Plasma Concentration of GSK1795091
Time Frame:Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Days 78, 162, 246, 414 and 498: 10 minutes post-dose
Safety Issue:
Description:Blood samples were collected at indicated time points for the determination of plasma concentration of GSK1795091. Pharmacokinetic (PK) Population consisted of all participants from the All Treated population for whom a PK sample was obtained, analyzed, measurable, and valid.
Measure:Part 1b: Plasma Concentration of GSK1795091
Time Frame:Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose
Safety Issue:
Description:Blood samples were collected at indicated time points for the determination of plasma concentration of GSK1795091.
Measure:Part 1c: Plasma Concentration of GSK1795091
Time Frame:Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose
Safety Issue:
Description:Blood samples were collected at indicated time points for the determination of plasma concentration of GSK1795091.
Measure:Part 1a: Maximum Plasma Concentration (Cmax) of GSK1795091
Time Frame:Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Days 78, 162, 246, 414 and 498: 10 minutes post-dose
Safety Issue:
Description:Blood samples were collected at indicated time points for the determination of Cmax of GSK1795091.
Measure:Part 1b: Cmax of GSK1795091
Time Frame:Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose
Safety Issue:
Description:Blood samples were collected at indicated time points for the determination of Cmax of GSK1795091.
Measure:Part 1c: Cmax of GSK1795091
Time Frame:Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose
Safety Issue:
Description:Blood samples were collected at indicated time points for the determination of Cmax of GSK1795091.
Measure:Part 1a: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) GSK1795091
Time Frame:Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Days 78, 162, 246, 414 and 498: 10 minutes post-dose
Safety Issue:
Description:Blood samples were collected at indicated time points for the determination of AUC(0-tau) of GSK1795091.
Measure:Part 1b: AUC(0-tau) GSK1795091
Time Frame:Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose
Safety Issue:
Description:Blood samples were collected at indicated time points for the determination of AUC(0-tau) of GSK1795091.
Measure:Part 1c: AUC(0-tau) GSK1795091
Time Frame:Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose
Safety Issue:
Description:Blood samples were collected at indicated time points for the determination of AUC(0-tau) of GSK1795091.
Measure:Part 1a: Predose Concentration (Cpre) of GSK1795091
Time Frame:Days 1, 8, 15, 22, 57, 64, 78, 162, 246, 414 and 498: Pre-dose
Safety Issue:
Description:Blood samples were collected at indicated time points for the determination of Cpre of GSK1795091.
Measure:Part 1b: Cpre of GSK1795091
Time Frame:Days 1, 8, 15, 22, 57, 64 and 78: Pre-dose
Safety Issue:
Description:Blood samples were collected at indicated time points for the determination of Cpre of GSK1795091.
Measure:Part 1c: Cpre of GSK1795091
Time Frame:Days 1, 8, 15, 22, 57, 64 and 78: Pre-dose
Safety Issue:
Description:Blood samples were collected at indicated time points for the determination of Cpre of GSK1795091.
Measure:Part 1a: Number of Participants With Present Antidrug Antibody (ADA) Against GSK3174998
Time Frame:Up to 27 months
Safety Issue:
Description:Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to GSK3174998. The presence of anti-GSK3174998 antibodies were assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
Measure:Part 1b: Number of Participants With the Present ADA Against GSK3359609
Time Frame:Up to 27 months
Safety Issue:
Description:Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to GSK3359609. The presence of anti-GSK3359609 antibodies were assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
Measure:Part 1c: Number of Participants With the Present ADA Against Pembrolizumab
Time Frame:Up to 27 months
Safety Issue:
Description:Serum samples were collected at indicated time points for the presence of antibodies that bind to pembrolizumab. The presence of anti-pembrolizumab antibodies were planned to be assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
Measure:Part 2a: Number of Participants With the Present ADA Against GSK3174998
Time Frame:Up to 2 years
Safety Issue:
Description:Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to GSK3174998. The presence of anti-GSK3174998 antibodies were were planeed to be assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
Measure:Part 2b: Number of Participants With the Present ADA Against GSK3359609
Time Frame:Up to 2 years
Safety Issue:
Description:Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to GSK3359609. The presence of anti-GSK3359609 antibodies were were planeed to be assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
Measure:Part 2c: Number of Participants With the Present ADA Against Pembrolizumab
Time Frame:Up to 2 years
Safety Issue:
Description:Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to pembrolizumab. The presence of anti-pembrolizumab antibodies were were planeed to be assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:GlaxoSmithKline

Trial Keywords

  • pembrolizumab
  • GSK1795091
  • Dose-escalation
  • 204686
  • Immunotherapies
  • GSK3359609
  • Phase I
  • anticancer agent
  • OX40
  • 201212
  • 204691
  • ICOS
  • TLR4
  • GSK3174998
  • Advanced Solid Tumors

Last Updated

July 20, 2021