Approval Probability
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Adjusted LOA
ML Risk
GSK1795091 · 2 trials · 2 indications
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
12-lead ECG was planned to be performed to measure QTcF interval.
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All participants enrolled into the study who have received a dose of study medication (GSK1795091 or placebo) were included in the All Subjects Population. Participants with non-serious AEs (5 percentage threshold) and SAEs has been reported.
Body temperature was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Systolic and diastolic BP was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Pulse rate was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Respiratory rate was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Hematology parameters included hemoglobin (HGB), hematocrit (HCT), Red Blood Cell (RBC) count, White Blood Cell (WBC) count with differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), platelet count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). Reference range for basophil was 0.01 - 0.07\*10\^9/Liters (L), eosinophils 0.03 - 0.5\*10\^9/L, HCT 0.38 - 0.48 proportion of RBC in blood, HGB 126 - 165\*gram (g)/L, lymphocytes 1.08 - 3\*10\^9/L, MCH 26.3 - 32.8\*picogram (pg), MCHC 324 - 359\*g/L, MCV 77 - 94.9\*femtoliter (fL), monocytes 0.3 - 0.92\*10\^9/L, neutrophils 1.46 - 5.85\*10\^9/L, platelets 155 - 342\*10\^9/L, erythrocytes 4.12 - 5.74\*10\^12/L, leukocytes 3.19 - 8.71\*10\^9/L. Values below these ranges were considered as low and above these ranges were considered as high (H). Data for participants from any visit post-screening with values \> reference range high and \< reference range low are report.
Clinical chemistry parameters with reference range were albumin 35-52\*g/L, Alkaline phosphatase (ALP) 30-120\*International units/L (IU/L), Alanine aminotransferase (ALT) 0-50 \* IU/L, Aspartate aminotransferase (AST) 0-50\*IU/L, direct bilirubin 0-3.4\* micromoles/L (µmol/L), bilirubin 5-21\*µmol/L, calcium 2.2-2.65\* millimoles/L (mmol/L), cholesterol 0-5.19\* mmol/L, creatinine 59-104\* µmol/L, C-reactive protein (CRP) 0-5\*milligram (mg)/L,Gamma Glutamyl Transferase (GGT) 4.1-5.9\*mmol/L, high density lipoproteins (HDL) cholesterol 0.99-2.32\*mmol/L, potassium 3.5-5.1\*mmol/L, low density lipoproteins (LDL) cholesterol 0-3.3\*mmol/L, protein 66-83\*g/L, sodium 136-146 \* mmol/L, triglycerides 0-2.25 \* mmol/L, glucose 4.1-5.9\*mmol/L, and urea 2.8-7.2\*mmol/L. Values below these ranges were considered as low and above these ranges were considered as high. Data for participants from any visit post-screening with values \> reference range high and \< reference range low are reported.
Urinalysis included microscopic examination parameters like Casts, REC, SEC, Urine erythrocytes and Urine leukocytes. Data at indicated time points were reported. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). NA indicates standard deviation could not be calculated as only 1 participant was analyzed at the given time point.
Urinalysis included parameters like ketones and urine glucose. Data at indicated time points were reported.
Urinalysis included parameter like Occult blood. Data at indicated time points were reported.
Urinalysis included parameter like Urine protein. Data at indicated time points were reported.
Urinalysis included parameter like specific gravity. Urinary specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine.
Urinalysis parameters included urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).
Single measurements of 12-lead ECGs were obtained after 10 minutes of rest in a semi-supine position for the participant. Participants with abnormal ECG findings that are clinically not significant (NCS) and clinically significant (CS) data has been presented here. The data of worst case post-Baseline is presented here.
| Arm | Type | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Part 2a: GSK1795091 + 24 mg GSK3174998 | EXPERIMENTAL | Participants will be administered GSK1795091 at a dose identified in Part 1 along with GSK3174998 24 mg. |
| Part 2b: GSK1795091 + 80 mg GSK3359609 | EXPERIMENTAL | Participants will be administered GSK1795091 at a dose identified in Part 1 along with GSK3359609 80 mg. |
| Part 2c: GSK1795091 + 200 mg Pembrolizumab | EXPERIMENTAL | Participants will be administered GSK1795091 at a dose identified in Part 1 along with pembrolizumab 200 mg. |
| Part 1: GSK1795091 or Placebo | EXPERIMENTAL | In Part 1, subjects in sequential cohorts will receive single ascending doses of intravenous (IV) injection of GSK1795091 or matching placebo, with a starting dose of 7 nanogram (ng), on Day 1 until the highest dose is evaluated. |
| Part 2 Cohort 1: GSK1795091 | EXPERIMENTAL | In Part 2 Cohort 1, subjects will receive IV injection of GSK1795091 on Day 1, at dose determined in part 1, and second dose on Day 8 (one week apart) |
| Part 2 Cohort 2: GSK1795091 | EXPERIMENTAL | In Part 2 Cohort 2, subjects will receive IV injection of GSK1795091 on Day 1, at dose determined in part 1, and a second dose on Day 15 (two weeks apart) |
| Name | Type | Description |
|---|---|---|
| GSK1795091 | DRUG | GSK1795091 will be available as solution for injection |
| GSK3174998 | DRUG | GSK3174998 will be available as lyophilized powder to be reconstituted for infusion. |
| GSK3359609 | DRUG | GSK3359609 will be available as solution for infusion. |
| Pembrolizumab | DRUG | Pembrolizumab will be available as solution for infusion or lyophilized powder for reconstitution. |
| Placebo | DRUG | Matching placebo will be supplied as a solution for injection vial and will be administered as IV bolus over 2-5 min followed by a IV bolus of 10 mL normal saline |
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 prefer...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| GE Healthcare Technologies Inc. | GEHC | 1 | PHASE1 | GEH200520/ GEH200521- Part A |
| Zimmer Biomet Holdings, Inc. | ZBH | 1 | - | Undisclosed |
| Ascentage Pharma Group International Unsponsored ADR | AAPG | 1 | PHASE1 | Olverembatinib |
GSK1795091 is an investigational small molecule being developed for the treatment of cancer and neoplasms. It has been studied in healthy subjects and in patients with advanced solid tumors. The drug is in Phase 1 clinical development and is not yet approved by regulatory authorities.
GSK1795091 is a Toll-like receptor 4 (TLR4) agonist. It is designed to stimulate the immune system by activating TLR4, which plays a role in the body's defense against cancer. This mechanism is being explored in early-stage clinical trials for oncology indications.
GSK1795091 is being developed by GSK plc, a global biopharmaceutical company listed on the stock exchange under the ticker GSK. The company is conducting clinical trials to evaluate the safety and efficacy of this investigational drug in oncology.
GSK1795091 is in Phase 1 clinical development. It has completed two Phase 1 trials, one in healthy subjects and one in patients with advanced solid tumors. The drug remains investigational and has not received approval from the FDA or other regulatory bodies.
GSK1795091 has been studied in two completed Phase 1 trials. NCT02798978 evaluated the drug in healthy subjects in Germany, while NCT03447314 tested it in combination with immunotherapies in patients with advanced solid tumors across the United States, Canada, Netherlands, and Spain.
Yes, GSK1795091 is a TLR4 agonist, meaning it activates Toll-like receptor 4. This mechanism is central to its proposed action in cancer treatment. The drug is being investigated for its potential to enhance immune responses against tumors in early-stage clinical trials.