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

NCT03447314 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2046862017-003545-23
• Study Type: interventional
• Target: 54
• Locations: 4 countries
• Sites: 8

Brief Summary

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.

Conditions

Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (19)

• Part 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs (STEAEs)

  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.

  Up to 27 months

• Part 2: Number of Participants With TEAEs and STEAEs

  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.

  Up to 27 months

• Part 1: Number of Participants With Dose-limiting Toxicity (DLT)

  An adverse event was considered to be a DLT if it was considered by investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment and met one of the criteria: hematologic toxicity-Grade4 neutropenia of \>7 days duration or febrile neutropenia, Grade 4 anemia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding as described in Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, non-hematologic toxicity-Grade 4 toxicity, Grade 3 toxicity that does not resolve to \<=Grade 1 or Baseline within 14 days despite optimal supportive care, alanine aminotransferase (ALT) \>=5 times upper limit of normal (ULN), ALT \>=3 times ULN persists for \>=4 weeks, ALT \>=3 times ULN and bilirubin \>=2 times ULN (\>35 percent \[%\] direct bilirubin), ALT \>=3 times ULN and international normalized ratio (INR) \>1.5, ALT \>=3 times ULN associated with symptoms (new or worsening) believed to be related to liver injury or hypersensitivity.

  42 days

• Part 1: Number of Participants With TEAEs Leading to Discontinuation

  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. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.

  Up to 2 years

• Part 2: Number of Participants With TEAEs Leading to Discontinuation

  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. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.

  Up to 2 years

• Part 1: Number of Participants With TEAEs Leading to Dose Reductions or Dose Delays

  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. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.

  Up to 2 years

• Part 2: Number of Participants With TEAEs Leading to Dose Reductions or Dose Delays

  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. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.

  Up to 2 years

• Part 1: Number of Participants With Change From Baseline in Hematology Parameters With Respect to the Normal Range

  Blood samples were collected for the analysis of following hematology parameters: neutrophils (Neutro), lymphocytes (lympho), monocytes (Mono), eosinophils (Eosino), basophils (Baso), hemoglobin (Hb), hematocrit (Hct), erythrocytes (Erythro), erythrocyte mean corpuscular volume (EMCV), erythrocyte mean corpuscular hemoglobin (EMCH) and platelet count (PC). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data was categorized as decrease to low (D to L) (value below lower limit of normal range \[LNR\]) and increase to high (I to H) (value above upper LNR). Participants were counted twice if participant had both decreased to low and increased to high within an assessment. Data for worst-case on therapy for categories decrease to low and increase to high is presented.

  Baseline (Day 1: Pre-dose) and up to 2 years

• Part 2: Number of Participants With Change From Baseline in Hematology Parameters With Respect to the Normal Range

  Blood samples were planned to be collected for the analysis of following hematology parameters: neutrophils, lymphocytes, monocytes, eosinophils, basophils, hemoglobin, hematocrit, erythrocytes, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin and platelet count.

  Baseline (Day 1: Pre-dose) and up to 2 years

• Part 1: Number of Participants With Change From Baseline in Chemistry Parameters With Respect to the Normal Range

  Blood samples were collected for the analysis of following chemistry parameters: urea, creatinine (Cr), glucose (Glu), potassium (Pot), sodium (Sod), calcium (Cal), aspartate aminotransferase (AST), ALT, alkaline phosphatase (ALP), bilirubin (Bil), direct bilirubin (D.Bil), protein, albumin (Alb), C-reactive protein (CRP) and Creatinine Clearance (CrCl). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data was categorized as decrease to low (value below the lower LNR), and increase to high (value above the upper LNR). Participants were counted twice if the participant had both decreased to low and increased to high within an assessment. Data for worst case on therapy for categories decrease to low and increase to high is presented.

  Baseline (Day 1: Pre-dose) and up to 2 years

• Part 2: Number of Participants With Change From Baseline in Chemistry Parameters With Respect to the Normal Range

  Blood samples were planned to be collected for the analysis of following chemistry parameters: urea, creatinine, glucose, potassium, sodium, calcium, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, direct bilirubin, protein, albumin, C-reactive protein and Creatinine Clearance.

  Baseline (Day 1: Pre-dose) and up to 2 years

• Part 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria

  Urine samples were collected for the analysis of following urinalysis parameters: glucose (Glu), protein (Pro), occult blood (OB), ketones, potential of hydrogen (pH) and specific gravity (SpGr) by dipstick method. The dipstick test gives results in a semi-quantitative manner. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The reference range is 1.002-1.030. Urine pH is an acid-base measurement. Normal urine has a slightly acid pH (5.0 - 6.0). Data was categorized as decrease to low (value below the lower LNR) and increase to high (value above the upper LNR). Participants were counted twice if the participant had both decreased to low and increased to high within an assessment. Data for worst-case on therapy for categories decrease to low and increase to high is presented.

  Up to 2 years

• Part 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria

  Urine samples were planned to be collected for the analysis of following urine parameters: glucose, protein, occult blood, ketones, potential of hydrogen and specific gravity by dipstick method.

  Up to 2 years

• Part 1: Number of Participants With Increase From Baseline in Vital Signs According to Markedly Abnormal Criteria

  Vital signs including systolic blood pressure (SBP), diastolic BP (DBP), pulse rate (PR) and body temperature (BT) were measured in a semi-supine position after 5 minutes rest for the participants. SBP: Category1 (\>140 and \<161 millimeter of mercury\[mmHg\]), Category 2 (\>=161 and \<181 mmHg), Category3 (\>=181 mmHg); DBP: Category1 (\>90 and \<101 mmHg), Category 2 (\>=101 and \<111 mmHg), Category 3 (\>=111 mmHg); PR: Category 1 (\>101 and \<116 beats per minutes\[bpm\]), Category 2 (\>=116 and \<131 bpm), Category 3 (\>=131 bpm); BT: Category 1 (\>38.0 and \<38.6 degrees Celsius), Category 2 (\>=38.6 and \<39.1 degrees Celsius), Category 3 (\>=39.1 degrees Celsius). Data for any increase in category at worst case on therapy is presented.

  Up to 2 years

• Part 2: Number of Participants With Vital Signs Any Increases From Baseline According to Markedly Abnormal Criteria

  Vital signs including SBP, DBP, pulse rate and body temperature were planned to be measured in a semi-supine position after 5 minutes rest for the participants.

  Up to 2 years

• Part 1: Number of Participants With Any Decrease From Baseline in Vital Sign According to Markedly Abnormal Criteria

  Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest for the participants. For SBP: a decrease in Category was defined as \<80 mmHg decrease from Baseline; DBP: decrease defined as Category (\<50 mmHg decrease from Baseline); pulse rate: decrease defined as Category (\<45 bpm decrease from Baseline). Data for decrease in category at worst case on therapy is presented.

  Up to 2 years

• Part 2: Number of Participants With Vital Signs Any Decreases From Baseline According to Markedly Abnormal Criteria

  Vital signs including SBP, DBP and pulse rate were planned to be measured in a semi-supine position after 5 minutes rest for the participants.

  Up to 2 years

• Part 1: Number of Participants With Any Increase From Baseline in Corrected QT Interval Using Fredericia's Formula (QTcF) According to Markedly Abnormal Criteria

  12-lead electrocardiogram (ECG) was obtained at indicated time point using an automated ECG machine that measured QTcF interval. QTc parameters were graded according to National Cancer Institute - CTCAE version 4.0. Grade 1 (\>450 milliseconds \[msec\]), Grade 2 (\>480 msec), Grade 3 (\>500 msec). An increase is defined as an increase in CTCAE grade relative to Baseline grade. Data for any grade increase at worst case on therapy is presented.

  Up to 2 years

• Part 2: Number of Participants With Any QTcF Interval Increases From Baseline According to Markedly Abnormal Criteria

  12-lead ECG was planned to be performed to measure QTcF interval.

  Up to 2 years

Secondary Outcomes (30)

• Part 1: Objective Response Rate

  Up to 47 months and 13 days

• Part 2: Objective Response Rate

  Up to 47 months and 13 days

• Part 1: Disease Control Rate

  Up to 47 months and 13 days

• Part 2: Disease Control Rate

  Up to 47 months and 13 days

• Part 1: Time to Response

  Up to 47 months and 13 days

Other Outcomes (6)

• Part 1: Number of Participants With TEAEs and STEAEs Until End of the Study

  Up to 47 months and 13 days

• Part 2: Number of Participants With TEAEs and STEAEs Until End of the Study

  Up to 47 months and 13 days

• Part 1: Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters

  Up to 2 years

Study Arms (18)

Part 1a: 50ng GSK1795091 + 24mg GSK3174998

EXPERIMENTAL

Participants 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.

Drug: GSK1795091; Drug: GSK3174998

Part 1a: 100ng GSK1795091 + 24mg GSK3174998

EXPERIMENTAL

Participants 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.

Drug: GSK1795091; Drug: GSK3174998

Part 1a: 150ng GSK1795091 + 24mg GSK3174998

EXPERIMENTAL

Participants 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.

Drug: GSK1795091; Drug: GSK3174998

Part 1a: 200ng GSK1795091 + 24mg GSK3174998

EXPERIMENTAL

Participants 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.

Drug: GSK1795091; Drug: GSK3174998

Part 1a: 250ng GSK1795091 + 24mg GSK3174998

EXPERIMENTAL

Participants 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.

Drug: GSK1795091; Drug: GSK3174998

Part 1b: 50ng GSK1795091 + 80mg GSK3359609

EXPERIMENTAL

Participants 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.

Drug: GSK1795091; Drug: GSK3359609

Part 1b: 100ng GSK1795091 + 80mg GSK3359609

EXPERIMENTAL

Participants 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.

Drug: GSK1795091; Drug: GSK3359609; Drug: Pembrolizumab

Part 1b: 150ng GSK1795091 + 80mg GSK3359609

EXPERIMENTAL

Participants 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.

Drug: GSK1795091; Drug: GSK3359609

Part 1b: 200ng GSK1795091 + 80mg GSK3359609

EXPERIMENTAL

Participants 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.

Drug: GSK1795091; Drug: GSK3359609

Part 1b: 250ng GSK1795091 + 80mg GSK3359609

EXPERIMENTAL

Participants 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.

Drug: GSK1795091; Drug: GSK3359609

Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab

EXPERIMENTAL

Participants 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.

Drug: GSK1795091; Drug: Pembrolizumab

Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab

EXPERIMENTAL

Participants 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.

Drug: GSK1795091; Drug: Pembrolizumab

Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab

EXPERIMENTAL

Participants 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.

Drug: GSK1795091; Drug: Pembrolizumab

Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab

EXPERIMENTAL

Participants 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.

Drug: GSK1795091; Drug: Pembrolizumab

Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab

EXPERIMENTAL

Participants 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.

Drug: GSK1795091; Drug: Pembrolizumab

Part 2a: GSK1795091 + 24 mg GSK3174998

EXPERIMENTAL

Participants will be administered GSK1795091 at a dose identified in Part 1 along with GSK3174998 24 mg.

Drug: GSK1795091; Drug: GSK3174998

Part 2b: GSK1795091 + 80 mg GSK3359609

EXPERIMENTAL

Participants will be administered GSK1795091 at a dose identified in Part 1 along with GSK3359609 80 mg.

Drug: GSK1795091; Drug: GSK3359609

Part 2c: GSK1795091 + 200 mg Pembrolizumab

EXPERIMENTAL

Participants will be administered GSK1795091 at a dose identified in Part 1 along with pembrolizumab 200 mg.

Drug: GSK1795091; Drug: Pembrolizumab

Interventions

GSK1795091 DRUG

GSK1795091 will be available as solution for injection

Part 1a: 100ng GSK1795091 + 24mg GSK3174998; Part 1a: 150ng GSK1795091 + 24mg GSK3174998; Part 1a: 200ng GSK1795091 + 24mg GSK3174998; Part 1a: 250ng GSK1795091 + 24mg GSK3174998; Part 1a: 50ng GSK1795091 + 24mg GSK3174998; Part 1b: 100ng GSK1795091 + 80mg GSK3359609; Part 1b: 150ng GSK1795091 + 80mg GSK3359609; Part 1b: 200ng GSK1795091 + 80mg GSK3359609; Part 1b: 250ng GSK1795091 + 80mg GSK3359609; Part 1b: 50ng GSK1795091 + 80mg GSK3359609; Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab; Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab; Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab; Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab; Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab; Part 2a: GSK1795091 + 24 mg GSK3174998; Part 2b: GSK1795091 + 80 mg GSK3359609; Part 2c: GSK1795091 + 200 mg Pembrolizumab

GSK3174998 DRUG

GSK3174998 will be available as lyophilized powder to be reconstituted for infusion.

Part 1a: 100ng GSK1795091 + 24mg GSK3174998; Part 1a: 150ng GSK1795091 + 24mg GSK3174998; Part 1a: 200ng GSK1795091 + 24mg GSK3174998; Part 1a: 250ng GSK1795091 + 24mg GSK3174998; Part 1a: 50ng GSK1795091 + 24mg GSK3174998; Part 2a: GSK1795091 + 24 mg GSK3174998

GSK3359609 DRUG

GSK3359609 will be available as solution for infusion.

Part 1b: 100ng GSK1795091 + 80mg GSK3359609; Part 1b: 150ng GSK1795091 + 80mg GSK3359609; Part 1b: 200ng GSK1795091 + 80mg GSK3359609; Part 1b: 250ng GSK1795091 + 80mg GSK3359609; Part 1b: 50ng GSK1795091 + 80mg GSK3359609; Part 2b: GSK1795091 + 80 mg GSK3359609

Pembrolizumab DRUG

Pembrolizumab will be available as solution for infusion or lyophilized powder for reconstitution.

Part 1b: 100ng GSK1795091 + 80mg GSK3359609; Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab; Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab; Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab; Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab; Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab; Part 2c: GSK1795091 + 200 mg Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Iqvia Pty Ltd: collaborator

Study Sites (8)

GSK Investigational Site

Boston, Massachusetts, 02215, United States

Location

GSK Investigational Site

St Louis, Missouri, 63110, United States

Location

GSK Investigational Site

Dallas, Texas, 75230, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Tacoma, Washington, 98405, United States

Location

GSK Investigational Site

Toronto, Ontario, M5G 2M9, Canada

Location

GSK Investigational Site

Amsterdam, 1066 CX, Netherlands

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

Related Publications (1)

• Steeghs N, Hansen AR, Hanna GJ, Garralda E, Park H, Strauss J, Adam M, Campbell G, Carver J, Easton R, Mays K, Skrdla P, Struemper H, Washburn ML, Matheny C, Piha-Paul SA. Manufacturing-dependent change in biological activity of the TLR4 agonist GSK1795091 and implications for lipid A analog development. Clin Transl Sci. 2022 Nov;15(11):2625-2639. doi: 10.1111/cts.13387. Epub 2022 Sep 12.

  PMID: 36097345 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

TLR4 agonist GSK1795091; pembrolizumab

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In Part 1, one dose level of GSK3174998, GSK3359609, or pembrolizumab with up to 5 dose levels of GSK1795091 are planned for evaluation. Sequential cohorts will be enrolled and dose escalation (or de-escalation) will proceed according to Neuenschwander-Continual Reassessment Method (N-CRM design). In Part 2, subjects will be administered GSK1795091 in combination with either 24 mg GSK3174998, 80 mg GSK3359609, or 200 mg pembrolizumab at a dose identified in Part 1.

Study Record Dates

• First Submitted: February 21, 2018
• First Posted: February 27, 2018
• Study Start: March 26, 2018
• Primary Completion: July 1, 2020
• Study Completion: March 11, 2022
• Last Updated: September 23, 2024
• Results First Posted: July 20, 2021

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.

Locations

CA (1); NL (1); ES (1); US (5)