Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, B-Cell

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Gastrointestinal Agents

All Drugs and Chemicals

Pancrelipase

Pancreatin

Eligible participants with solid relapsed/refractory tumors will receive escalating doses of GSK3368715 at a starting dose of 50 mg, administered orally once daily.

Additional participants in Part 1, treated at or close to the expected the maximum tolerated dose (MTD)/RP2D, will be evaluated for metabolic and biomarker profiling. Participants may be enrolled into this cohort(s) even after MTD/RP2D has been identified and Part 2 has been initiated.

Eligible participants will receive single dose of GSK3368715 at starting dose of 50 mg tablet orally in fasted state followed by fed state in Period 1 and Fed followed by fasted state in Period 2.

Eligible participants with relapsed/refractory DLBCL will receive RP2D of GSK3368715 established during Part 1, administered orally once daily.

Eligible participants with relapsed/refractory solid tumors (pancreas cancer, NSCLC, and bladder cancer) will receive RP2D of GSK3368715 established during Part 1, administered orally once daily.

GSK3368715 will be available with dosing strengths of 25 mg, 100 mg and 250 mg to be administered once daily as an oral capsule.

GSK3368715

GSK3368715 will be available in Immediate release (IR) white film coated tablet with dosing strengths of 50 mg, 100 mg and 250 mg to be administered orally once daily .

GSK Clinical Trials

Arginine methylation mediated by protein arginine methyl-transferases (PRMTs) is an important post-translational modification of proteins involved in a diverse range of cellular processes. Misregulation and overexpression of PRMT1 (a type I PRMT) has been associated with a number of solid and hematopoietic cancers. GSK3368715 leads to inhibition of tumor cell growth across tumor types with cytotoxic response observed in lymphoma, acute myeloid leukemia (AML) and a subset of solid tumor cell lines. This study will assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), food effect and preliminary clinical activity of GSK33368715 in participants with relapsed/refractory DLBCL and selected solid tumors with frequent methyl-thioadenosine phosphorylase (MTAP)-deficiency. The study will consist of two parts. In Part 1 (Dose Escalation) escalating doses of GSK3368715 will be evaluated and recommended phase 2 dose (RP2D) will be established in participants with selected solid relapsed/refractory tumors. Once a RP2D is identified, a food effect sub-study will be initiated to determine the effect of a high-fat, high calorie meal on the bioavailability of GSK3368715. In Part 2 (Dose Expansion), this RP2D will be further investigated in two expansion cohorts; participants with DLBCL (Expansion Cohort 2A) and relapsed/refractory solid tumors including pancreatic, bladder, and non-small cell lung cancer (NSCLC)(Expansion Cohort 2B). The study includes a screening period, an intervention period and follow up.

Eligible participants will receive sequential doses of GSK3368715, administered orally once daily in Part 1 of the study and in Part 2, participants will receive RP2D determined in Part 1.

This will be an open-label study. Hence, masking will not be performed.

First Time in Humans (FTIH) Study of GSK3368715 in Participants With Solid Tumors and Diffuse Large B-cell Lymphoma (DLBCL)

A Phase I, Open-label, Dose-escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK3368715 in Participants With Solid Tumors and DLBCL

IPD for this study will be made available via the Clinical Study Data Request site.

A DLT is considered by the investigator to be clinically relevant,attributed event during the first 21days of intervention meeting the following criteria:Non-hematologic toxicity:Aspartate Aminotransferase(AST)/Alanine Aminotransferase(ALT) Grade 3/4,ALT\>=5 times Upper limit of Normal(ULN),ALT\>=3times ULN(\>=4 weeks),ALT\>=3 times ULN plus(+)bilirubin\>=2 times ULN,ALT \>= 3 times ULN+liver symptoms or International Normalization Ratio(INR)\>1.5.Nausea:Grade 3;Vomiting or diarrhea:Grade3/4(\>3days);Fatigue:Grade 3(\>5days).Hypertension:Uncontrolled Grade 3/4.Electrocardiogram(ECG)-change:\>20 milliseconds(msec) QRS extension.Lab abnormality:uncontrolled Grade3(\>3days)/Grade4.Hematologic toxicity:Neutropenia:uncontrolled Grade3(\>3days)/febrile neutropenia/Grade 4.Thrombocytopenia:uncontrolled Grade 3(\>3days)/Grade 3(clinically significant Hemorrhage)/Grade 4.Venous thromboembolism (VTE):Grade2 needing systemic anticoagulation/Grade\>=3 during the first 8 weeks or if sooner,study discontinuation

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Any untoward event resulting in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE.

All adverse events were analyzed using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. Graded from Grade 1: mild asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL), Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4: Life-threatening consequences; urgent intervention indicated, Grade 5: death related AE. Higher grade indicates more severe condition. Number of participants with maximum severity grades are presented.

ORR is defined as the percentage of participants with a confirmed complete response (CR) or a partial response (PR). Participants with solid tumor were planned to be assessed per Response Criteria for Solid Tumors (RECIST) 1.1 and DLBCL participants were planned to be assessed per Lugano Criteria. This analysis was planned but not performed for Part 2 as the study was terminated during Part 1.

Overall response rate is defined as the percentage of participants with a confirmed complete response (CR) or a partial response (PR). Participants with solid tumor were assessed per Response Criteria for Solid Tumors (RECIST) 1.1 and DLBCL participants were assessed per Lugano Criteria. The best ORR was recorded from the start of the intervention until disease progression/recurrence and was determined based on the investigator's assessment of response at each time point. The percentage of participants achieving best overall response rate have been presented.

Blood samples were collected at indicated time points. The pharmacokinetic (PK) parameters were calculated by non-compartmental analysis. PK Population included all participants in the All-Treated population from whom at least one PK sample was obtained, analyzed, and was measurable.

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. Not applicable (NA) indicates that data could not be calculated as these were derivate values which were below the lower limit of quantification.

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. Time invariance was calculated as the ratio of AUC(0-24) on Day 15 / AUC (0-infinity) on Day 1 for GSK3368715.

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. Accumulation ratio (AR) was calculated as the ratio of AUC(0-24) on Day 15/Day 1 for GSK3368715.

Blood samples were planned to be collected at indicated time points in food effect cohorts (fasted followed by fed state and fed followed by fasted state). Samples were not collected due to early termination of study during Part 1; therefore, no analysis could be performed.

Blood samples were planned to be collected at indicated time points in food effect cohorts (fasted followed by fed state and fed followed by fasted state). Samples were not collected due to early termination of the study during Part 1; therefore, no analysis could be performed.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Any untoward event resulting in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as serious adverse event (SAE). This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

All adverse events were analyzed using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. Graded from Grade 1: mild asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL), Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4: Life-threatening consequences; urgent intervention indicated, Grade 5: death related AE. Higher grade indicates more severe condition. Number of participants with maximum severity grades were presented. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

PFS is defined as the time from the first dose of study intervention to disease progression or death due to any cause, whichever occurs earlier. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Blood samples were planned to be collected for PK analysis of GSK3368715. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Blood samples were planned to be collected for PK analysis of GSK3368715 . This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Blood samples were planned to be collected for pharmacokinetic analysis of GSK3368715. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

GlaxoSmithKline

All Treated Population included all participants who received at least one dose of GSK3368715. Study was terminated early during Part 1 as the benefit/risk assessment did not favor continuation of the study; therefore, Part 1: Food effect cohorts and Part 2 were not conducted.

Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 50 milligrams (mg).

Part 1 GSK3368715 50mg

Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 100mg.

Part 1 GSK3368715 100mg

Participants with solid relapsed/refractory tumors were administered once daily oral dose of GSK3368715 200mg.

Part 1 GSK3368715 200mg

Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fasted state followed by fed state at or near the recommended Phase II dose (RP2D).

Part 1:Food Effect Cohort: GSK3368715 Fasted Followed by Fed

Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fed state followed by fasted state at or near the RP2D.

Part 1:Food Effect Cohort: GSK3368715 Fed Followed by Fasted

Participants with DLBCL were planned to receive recommended Phase II dose (RP2D) based on Part 1 data.

Part 2 GSK3368715 Expansion Cohort

Total

Study was terminated early during Part 1 as the benefit/risk assessment did not favor continuation of the study, therefore Part 1: Food effect cohorts and Part 2 were not conducted.

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

GSK Response Center

Part 1: Food Effect Cohort: GSK3368715 Fasted Followed by Fed

Part 1: Food Effect Cohort: GSK3368715 Fed Followed by Fasted

All-Treated Population included all participants who received at least one dose of GSK3368715. Data was not collected for Part 1: Food Effect Cohorts, as the study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts

Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)

Any Non-SAE

Any SAE

All-Treated Population. Data was not collected for Part 1: Food Effect Cohorts, as the study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts

Part 1: Number of Participants With Non-Serious Adverse Events (Non-SAEs) and SAEs

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

Part 1: Number of Participants With AEs by Severity Grades

All-Treated Population. Data was not collected in Part 2 as the study was terminated early during Part 1 and hence no participant was enrolled in Part 2.

Part 2: Percentage of Participants Achieving Objective Response Rate (ORR)

All Treated Population. Data was not collected for Part 1: Food Effect Cohorts, as the study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts

Part 1: Percentage of Participants Achieving Best Overall Response Rate

GSK3368715 Day 1,n=3,16,12

GSK3368715 Day 15,n=3,14,9

PK Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). Data was not collected for Part 1: Food Effect Cohorts, as the study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts

Part 1: Maximum Observed Plasma Concentration (Cmax) Following Administration of GSK3368715

PK Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).Data was not collected for Part 1: Food Effect Cohorts, as the study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts

Part 1: Time to Reach Cmax (Tmax) Following Administration of GSK3368715

Part 1: Area Under the Concentration Time Curve From Time Zero to Last Time of Quantifiable Concentration (AUC [0-t]) Following Administration of GSK3368715

PK Population.Only those participants (par) with data available at specified data points were analyzed.Data not collected for Part (P)1:Food Effect Cohorts (FEC),as study was terminated early during P1;hence no par were enrolled in P1:FEC.AUC(0-infinity) could not be calculated for par in "P1 GSK3368715 50mg" arm,as atleast 3 data points are required in terminal elimination phase within same par;this criteria could not be fulfilled due to insufficient data above limit of quantification

Part 1: AUC From Time Zero Extrapolated to Infinite Time (AUC [0-infinity]) Following Administration of GSK3368715

PK Population. Only those participants with data available at the specified data points were analyzed. Data was not collected for Part 1: Food Effect Cohorts, as the study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts

Part 1: Area Under the Concentration-time Curve From Time Zero to the Predose of the Next Dose [AUC (0-tau)] Following Administration of GSK3368715

GSK3368715 Day 1,n=3,16,11

GSK3368715 Day 15,n=3,14,10

Part 1: Trough (Pre-dose) Concentration (Ctau) Following Administration of GSK3368715

PK Population. Only those participants with data available at the specified data points were analyzed. Data was not collected for Part 1: Food Effect Cohorts, as the study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts. Time invariance computation is dependent on AUC(0-infinity) and since AUC(0-infinity) could not be computed for participants in "Part 1 GSK3368715 50mg" arm, time invariance was not computable as well.

Part 1: Time Invariance Ratio Following Administration of GSK3368715

PK Population.Only those participants with data available at the specified data points were analyzed. Data was not collected for Part 1: Food Effect Cohorts,as study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts. Accumulation ratio could not be derived for "Part 1 GSK3368715 50mg" arm because there were no participant with AUC(0-24) values at both Day 1 and Day 15; hence, paired results were not available to calculate Accumulation ratio

Part 1: Accumulation Ratio Following Administration of GSK3368715

Participants with solid relapsed/refractory tumors were planned to receive once daily oral dose of GSK3368715 with a tablet formulation in the fed state followed by fasted state at or near the RP2D

PK Population. Data was not collected for Part 1: Food Effect Cohorts, as the study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts

Part 1: Food Effect Cohorts: Cmax Following Administration of GSK3368715

PK Population. Data was not collected for Part 1: Food Effect Cohorts, as the study was terminated early during Part 1 and hence no participants were enrolled in Part 1: Food Effect Cohorts.

Part 1: Food Effect Cohorts: Tmax Following Administration of GSK3368715

Part 1: Food Effect Cohorts: AUC (0-t) Following Administration of GSK3368715

Part 1: Food Effect Cohorts: AUC (0-infinity) Following Administration of GSK3368715

Part 1: Food Effect Cohorts: AUC (0-tau) Following Administration of GSK3368715

All Treated Population. Data was not collected as the study was terminated early during Part 1 and hence no participants were enrolled in Part 2.

Part 2: Number of Participants With Non-SAEs and SAEs

Part 2: Number of Participants With AEs by Severity Grades

Part 2: Progression-free Survival (PFS)

PK Population. Data was not collected as the study was terminated early during Part 1 and hence no participants were enrolled in Part 2.

Spots Global Cancer Trial Database for gsk3368715

Every month we try and update this database with for gsk3368715 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for gsk3368715

Every month we try and update this database with for gsk3368715 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for gsk3368715 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.