Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Pembrolizumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

In Part 1, advanced or metastatic PDAC will be enrolled. Part 1 will be using escalating doses of GSK3145095 (total daily dose of 100 mg, 200 mg, 400 mg, 800 mg, and 1600 mg) orally as monotherapy for up to 2 years. For each dose level, subjects will receive a single dose of half the total daily dose on Day 1; and as BID (total daily dose divided in two equal doses) starting from Day 2.

In Part 2, subjects with selected solid tumors, including but not limited to, PDAC, NSCLC, TNBC and/or melanoma will be enrolled. Part 2 will be using GSK3145095 combination escalation to start at least one dose level below the highest dose of GSK3145095 shown to be safe in Part 1, orally BID for up to 2 years along with pembrolizumab 200 mg intravenous (IV) every 3 weeks (Q3W) for up to 2 years.

In Part 3, subjects with selected solid tumors will be enrolled. Part 3 will be using GSK3145095 at one or two dose levels shown to be tolerable in Part 2 orally BID for up to 2 years along with pembrolizumab 200 mg IV Q3W for up to 2 years.

In Part 4, subjects with selected solid tumors will be enrolled. Part 4 will be using GSK3145095 at one or two dose levels shown to be tolerable in Part 2 orally BID for up to 2 years along with combination of additional anticancer agents.

GSK3145095 will be available as capsule (size 1 containing 5 to 25 mg GSK3145095 and size 0 containing 25 to 75 mg GSK3145095) or tablet (25, 50, 200 mg white to slightly covered round/oval shaped coated) for oral administration in the fasted stated with approximately 200 milliliters (mL) of water.

GSK3145095

Pembrolizumab will be available as solution for infusion (100 milligrams/ 4 milliliter) at a dose of 200 mg via IV infusion for 30 minutes (given the variability of infusion pumps from site to site, a window of -5 minutes and +10 minutes is permitted i.e., infusion time is 25 to 40 minutes).

GSK Clinical Trials

In an unbiased CRISPR screen, RIPK1 was identified as a top gene contributing to immunotherapy resistance. In addition, RIPK1 has been reported to drive pancreatic oncogenesis. In murine models, inhibition of RIPK1 kinase activity in the pancreatic tumor microenvironment leads to the replacement of tumor-permissive myeloid infiltrates with innate cells that promote an effective antitumor response by adaptive cells. The investigators hypothesize that inhibition of RIPK1 in human pancreatic cancer subjects will modulate the immune infiltrate to sensitize tumors to checkpoint blockade.

Study 205013 is a Phase 1 FTIH study of GSK3145095 alone and in combination with other anticancer agents including pembrolizumab in subjects with pancreatic ductal adenocarcinoma (PDAC) and other selected tumors. The study includes up to 4 parts: Part 1 dose escalation will be conducted in approximately 30 adult subjects with advanced or metastatic PDAC using escalating doses of GSK3145095 as monotherapy only. Part 2 will combine escalating doses of GSK3145095 with 200 milligram (mg) pembrolizumab. Dose escalation of GSK3145095 will begin at least one level below the highest dose shown to have an acceptable toxicity profile in at least 3 subjects in Part 1. Part 2 may be conducted in a broader population of selected solid tumors using a combination of escalating doses of GSK3145095 and 200 mg pembrolizumab. Part 3 will enroll subjects treated with one or more dose levels of GSK3145095 in combination with 200 mg pembrolizumab. Part 4 will investigate the combination of additional anticancer agents with one or more doses of GSK3145095 identified as safe in Part 1. Up to approximately 220 subjects will be treated in the study. Parts 1 and 2 will each treat up to approximately 30 subjects. Parts 3 and 4 will treat up to approximately 160 subjects (up to 80 subjects in each Part). The total duration of the study is expected to last up to 2 years.

Part 1 dose escalation will administer escalating doses of GSK3145095 as monotherapy only. Part 2 will combine escalating doses of GSK3145095 with 200 mg pembrolizumab. Dose escalation of GSK3145095 will begin at least one level below the highest dose shown to have an acceptable toxicity profile in at least 3 subjects in Part 1. Part 3 will enroll subjects treated with one or more dose levels of GSK3145095 in combination with 200 mg pembrolizumab. Part 4 will investigate the combination of additional anticancer agents with one or more doses of GSK3145095 identified as safe in Part 1.

First-time-in-human (FTIH) Study of GSK3145095 Alone and in Combination With Other Anticancer Agents in Adults With Advanced Solid Tumors

A Phase I/II, Open-Label Study to Investigate the Safety, Clinical Activity, Pharmacokinetics, and Pharmacodynamics of GSK3145095 Administered Alone and in Combination With Anticancer Agents Including Pembrolizumab in Adult Participants With Selected Advanced Solid Tumors

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

An AE 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. SAE is defined as any untoward medical occurrence that, at any dose which results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations.

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.

All adverse events were to be analyzed using 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 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.

All toxicities were graded using NCI-CTCAE version 5.0. An AE was considered a DLT if it occurred during the first 28 days of treatment, was considered by the investigator to be clinically relevant, and met one of the following DLT criteria: hematologic toxicity: Grade 4 neutropenia, febrile neutropenia, Grade 4 anemia, Grade 3 thrombocytopenia, Grade 3 thrombocytopenia with bleeding; Grade 3 or greater non-hematologic toxicity, any Grade 2 ocular toxicity requiring systemic steroids.

A participant's disease status and determination of disease progression at post Baseline visits was to be evaluated by the local investigator's assessments by RECIST version 1.1. The overall response rate (ORR)-CR and PR was to be determined by the investigator assessment of the participants computed tomography (CT) or magnetic resonance imaging (MRI) using RECIST version 1.1 criteria for target lesions. ORR is defined as the percentage of participants with a best overall confirmed CR or PR at any time as per disease-specific criteria. PR is when there is at least 30 percent decrease in sum of the longest diameter of the target lesions. Complete Response is when there is disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to \<10 millimeters (mm).

A participant's disease status and determination of disease progression at post Baseline visits was to be evaluated by the local investigator's assessments by RECIST version 1.1. The overall response rate (complete response and partial response) was to be determined by the investigator assessment of the participants CT or MRI using RECIST version 1.1 criteria for target lesions. ORR is defined as the percentage of participants with a best overall confirmed CR or PR at any time as per disease-specific criteria. Partial Response is when there is at least 30 percent decrease in sum of the longest diameter of the target lesions. Complete Response is when there is disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to \<10 mm.

Best overall response is defined as the best unconfirmed response (Complete Response \[CR\] \> Partial Response \[PR\] \> Stable Disease \[SD\] \[or non-CR/non-PD\] \> Progressive Disease \[PD\] \> Not Evaluable \[NE\]) from treatment start date until disease progression or initiation of new anti-cancer therapy, whichever is earlier, as assessed by the investigator per RECIST version 1.1 Criteria. The BOR rate is defined as the percentage of participants with each best unconfirmed response category. Participants with unknown or missing responses were treated as non-responders, i.e., these participants were included in the denominator when calculating percentages of response.

Best overall response is defined as the best unconfirmed response (CR \> PR \> SD \[or non-CR/non-PD\] \> PD\] \> NE) from treatment start date until disease progression or initiation of new anti-cancer therapy, whichever is earlier, as assessed by the investigator per RECIST 1.1 Criteria. The BOR rate is defined as the percentage of participants with each best unconfirmed response category. Participants with unknown or missing responses were treated as non-responders, i.e., these participants were included in the denominator when calculating percentages of response.

PFS is defined as time from 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. If the participant received subsequent anti-cancer therapy prior to the date of documented events, PFS was to be censored at the last adequate assessment (e.g., assessment where visit level response is confirmed response, partial response or stable disease) prior to the initiation of therapy. Otherwise, if the participant did not have a documented date of event, PFS was to be censored at the date of the last adequate assessment.

Overall survival is defined as time from the date of first dose to the date of death due to any cause. If a participant does not have a documented date of death, time of death is censored at the date of last contact.

All adverse events were planned to be analyzed using 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 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.

Blood samples were collected at the indicated time points for the determination of AUC(0-t) following single dose of GSK3145095 on Day 1 and was calculated by standard non-compartmental analysis.

Blood samples were to be collected at the indicated time points for the determination of AUC (0-t) following single dose of GSK3145095 on Day 1 and was to be calculated by standard non-compartmental analysis.

Blood samples were collected at the indicated time points for the determination of AUC (0-tau) following single dose of GSK3145095 on Day 1 and was calculated by standard non-compartmental analysis.

Blood samples were to be collected at the indicated time points for the determination of AUC (0-tau) following single dose of GSK3145095.

Blood samples were collected at the indicated time points for the determination of Cmax following single dose of GSK3145095 on Day 1 and was calculated by standard non-compartmental analysis.

Blood samples were to be collected at the indicated time points for the determination of Cmax following single dose of GSK3145095 on Day 1.

Blood samples were collected at the indicated time points for the determination of Cmin following single dose of GSK3145095 on Day 1 and was calculated by standard non-compartmental analysis.

Blood samples were to be collected at the indicated time points for the determination of Cmin following single dose of GSK3145095 on Day 1.

Blood samples were collected at the indicated time points for the determination of tmax following single dose of GSK3145095 on Day 1 and was calculated by standard non-compartmental analysis.

Blood samples were to be collected at the indicated time points for the determination of tmax following single dose of GSK3145095 on Day 1.

Blood samples were collected at the indicated time points for the determination of CL/F following single dose of GSK3145095 on Day 1 and was calculated by standard non-compartmental analysis.

Blood samples were to be collected at the indicated time points for the determination of CL/F following single dose of GSK3145095 on Day 1.

Blood samples were collected at the indicated time points for the determination of Vz/F following single dose of GSK3145095 on Day 1 and was calculated by standard non-compartmental analysis.

Blood samples were to be collected at the indicated time points for the determination of V/F following single dose of GSK3145095 on Day 1.

Blood samples were collected at the indicated time points for the determination of t1/2 following single dose of GSK3145095 on Day 1 and was calculated by standard non-compartmental analysis.

Blood samples were to be collected at the indicated time points for the determination of t1/2 following single dose of GSK3145095 on Day 1.

Blood samples were collected at the indicated time points for the determination of AUC (0-t) following repeat dose of GSK3145095 on Day 15 and was calculated by standard non-compartmental analysis.

Blood samples were to be collected at the indicated time points for the determination of AUC (0-t) following repeat dose of GSK3145095 on Day 15.

Blood samples were collected at the indicated time points for the determination of AUC (0-tau) following repeat dose of GSK3145095 on Day 15 and was calculated by standard non-compartmental analysis.

Blood samples were to be collected at the indicated time points for the determination of AUC (0-tau) following repeat dose of GSK3145095 on Day 15.

Blood samples were collected at the indicated time points for the determination of Cmax following repeat dose of GSK3145095 on Day 15 and was calculated by standard non-compartmental analysis.

Blood samples were to be collected at the indicated time points for the determination of Cmax following repeat dose of GSK3145095 on Day 15.

Blood samples were collected at the indicated time points for the determination of Cmin following repeat dose of GSK3145095 on day 15 and was calculated by standard non-compartmental analysis.

Blood samples were to be collected at the indicated time points for the determination of Cmin following repeat dose of GSK3145095 on Day 15.

Blood samples were collected at the indicated time points for the determination of tmax following repeat dose of GSK3145095 and was calculated by standard non-compartmental analysis.

Blood samples were to be collected at the indicated time points for the determination of tmax following repeat dose of GSK3145095 on Day 15.

Blood samples were collected at the indicated time points for the determination of CL/F following repeat dose of GSK3145095 on Day 15. For accurate estimation of CL/F following repeated administration, it is imperative that steady state has been achieved. As the attainment of steady state could not be confirmed with certainty, CL/F was not computed following repeated dose.

Blood samples were to be collected at the indicated time points for the determination of CL/F following repeat dose of GSK3145095 on Day 15.

Blood samples were collected at the indicated time points for the determination of Vz/F following repeat dose of GSK3145095 on Day 15. As t1/2 following repeated administration could not be computed, Vz/F whose estimation is dependent upon the t1/2 could not be estimated as well.

Blood samples were to be collected at the indicated time points for the determination of V/F following repeat dose of GSK3145095 on Day 15.

Blood samples were collected at the indicated time points for the determination of t1/2 following repeat dose of GSK3145095 on Day 15. t1/2 following repeated administration was not computed because duration of observation (12 hours from the morning dose) was too short (less than 2 times the average half-life observed after the first dose) for its accurate estimation.

Blood samples were to be collected at the indicated time points for the determination of t1/2 following repeat dose of GSK3145095 on Day 15.

Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality. As only one dose level (100 mg) was tested prior to termination of the study and multiple dose levels are required to investigate dose proportionality, hence dose proportionality could not be analyzed.

Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality.

Accumulation ratio was calculated as AUC(0-tau) at Day 15 divided by AUC(0-tau) at Day 1 for GSK3145095.

Accumulation ratio was to be calculated as AUC(0-tau) at Day 15 divided by AUC(0-tau) at Day 1 for GSK3145095.

Blood samples were collected at indicated time points for analysis of time invariance. Time invariance was calculated as AUC(0-tau) at Day 15 divided by AUC(0-infinity) at Day 1 for GSK3145095.

Blood samples were to be collected at indicated time points for analysis of time invariance. Time invariance were to be calculated as AUC(0-tau) at Day 15 divided by AUC(0-infinity) at Day 1 for GSK3145095.

Blood samples were to be collected at indicated time points for the determination of plasma concentration of pembrolizumab.

Blood samples were to be collected at indicated time points for the determination of Cmax of pembrolizumab.

Blood samples were to be collected at indicated time points for the determination of AUC (0-tau) of pembrolizumab.

Blood samples were to be collected at indicated time points for the determination of Cmin of pembrolizumab.

Blood samples were to be collected at the indicated time points for the determination of AUC (0-t) following single dose of GSK3145095 on Day 1.

Blood samples were to be collected at the indicated time points for the determination of AUC (0-t) following single dose of pembrolizumab.

Blood samples were to be collected at the indicated time points for the determination of AUC (0-tau) following single dose of pembrolizumab.

Blood samples were to be collected at the indicated time points for the determination of Cmax following single dose of pembrolizumab.

Blood samples were to be collected at the indicated time points for the determination of tmax following single dose of pembrolizumab.

Blood samples were to be collected at the indicated time points for the determination of t1/2 following single dose of pembrolizumab.

Blood samples were to be collected at the indicated time points for the determination of AUC (0-t) following repeat dose of pembrolizumab.

Blood samples were to be collected at the indicated time points for the determination of AUC (0-tau) following repeat dose of pembrolizumab.

Blood samples were to be collected at the indicated time points for the determination of Cmax following repeat dose of pembrolizumab.

Blood samples were to be collected at the indicated time points for the determination of tmax following repeat dose of pembrolizumab.

Blood samples were to be collected at the indicated time points for the determination of t1/2 following repeat dose of pembrolizumab.

Blood samples were to be collected at indicated time points for analysis of time invariance. Time invariance was to be calculated as AUC(0-tau) at Day 15 divided by AUC(0-infinity) at Day 1 for GSK3145095.

Accumulation ratio was to be calculated as AUC(0-tau) at Day 15 divided by AUC(0-tau) at Day 1 for pembrolizumab.

Blood samples were to be collected at indicated timepoints for analysis of time invariance. Time invariance was to be calculated as AUC(0-tau) at Day 15 divided by AUC(0-infinity) at Day 1 for pembrolizumab.

Parexel

GlaxoSmithKline

Non-serious AEs and SAEs were reported for all treated Population. Data is presented for Part 1 "GSK3145095 50 mg BID" only, as study was terminated during this first escalation cohort, hence subsequent escalation cohorts of Part-1 were not initiated. Parts 2, 3 and 4 were also not initiated.

Participants received a single 50 milligram (mg) dose of GSK3145095 orally on Day 1. From study day 2, participants then received total daily dose of 100 mg GSK3145095 orally given as 50 mg twice a day (BID).

Part 1-GSK3145095 50 mg BID

Participants were to receive a single 100 mg dose of GSK3145095 orally on Day 1. From study Day 2, participants were to receive 200 mg GSK3145095 given as 100 mg BID.

Part 1-GSK3145095 100 mg BID

Participants were to receive a single 200 mg dose of GSK3145095 orally on Day 1. From study Day 2, participants were to receive 400 mg GSK3145095 given as 200 mg BID.

Part 1-GSK3145095 200 mg BID

Participants were to receive a single 400 mg dose of GSK3145095 orally on Day 1. From study Day 2, participants were to receive 800 mg dose of GSK3145095 given as 400 mg BID

Part 1-GSK3145095 400 mg BID

Participants were to receive a single 800 mg dose of GSK3145095 orally on Day 1. From study Day 2, participants were to receive 1600 mg dose of GSK3145095 given as 800 mg BID.

Part 1-GSK3145095 800 mg BID

Part 2 was to be initiated after evaluation of safety and toxicity data of Part 1. Participants in this combination therapy arm were planned to receive GSK3145095 at one dose level below the highest dose shown to have an acceptable toxicity profile in at least 3 participants in Part 1 in combination with 200 mg pembrolizumab as Intravenous (IV) infusion over 30 minutes (min) for every 3 weeks.

Part 2- GSK3145095+ Pembrolizumab 200 mg

Part 3 was to be initiated after evaluation of safety and toxicity data of part 2. Participants in this combination therapy arm were planned to receive GSK3145095 at recommended dose level determined during Part 2, with 200 mg pembrolizumab as IV infusion for every 3 weeks.

Part 3- GSK3145095+ Pembrolizumab 200mg

In Part 4, participants were planned to receive GSK3145095 at recommended dose level determined during Part 2, in combination with anticancer agent

Part 4- GSK3145095+ Anticancer Agent

Total

Age, Continuous

Sex: Female, Male

Race

Race/Ethnicity, Customized

Part 1-GSK3145095 50 mg BID data is presented as study was terminated during Part 1 and hence Part 2, 3 and 4 were not initiated.

GSK Response Center

Non-serious AEs

SAEs

All treated Population consisted of all participants who received at least one dose of GSK3145095. Study was terminated in Part-1 during first escalation cohort "GSK3145095 50 mg BID", hence subsequent escalation cohorts were not initiated.

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

Part 2 was to be initiated after evaluation of safety and toxicity data of Part 1. Participants in this combination therapy arm were planned to receive GSK3145095 at one dose level below the highest dose shown to have an acceptable toxicity profile in at least 3 participants in Part 1 in combination with 200 mg pembrolizumab as IV infusion over 30 minutes for every 3 weeks.

Part 2-GSK3145095+ Pembrolizumab 200 mg

All treated Population: Data were not collected for this endpoint as study was terminated during Part 1. Subsequent Part 2 was not initiated.

Number of Participants With Non-serious AEs and SAEs-Part 2

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

All treated Population: Study was terminated in Part-1 during first escalation cohort "GSK3145095 50 mg BID", hence subsequent escalation cohorts were not initiated.

Number of Participants With AEs by Severity Grades-Part 1

Number of Participants With AEs by Severity Grades-Part 2

Number of Participants With Dose-limiting Toxicities (DLTs)-Part 1

Number of Participants With DLTs-Part 2

Part 3 GSK3145095+ Pembrolizumab 200 mg

All treated Population: Data were not collected for this endpoint as study was terminated during Part 1. Subsequent Part 3 was not initiated.

Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Criteria-Part 3

In Part 4, participants were planned to receive GSK3145095 at recommended dose level determined during Part 2, in combination with anticancer agent.

Part 4 GSK3145095+ Anticancer Agent

All treated Population: Data were not collected for this endpoint as study was terminated during Part 1. Subsequent Part 4 was not initiated.

Percentage of Participants Achieving Complete Response or Partial Response Based on RECIST 1.1 Criteria-Part 4

Complete response

Partial response

Stable disease

Progressive disease

Not evaluable

Best Overall Response (BOR) Rate-Part 1

Best Overall Response (BOR) Rate-Part 2

Progression-free Survival (PFS)-Part 3

Progression-Free Survival (PFS) -Part 4

Overall Survival -Part 3

Part 4 GSK3145095 200 mg + Anticancer Agent

Overall Survival -Part 4

Number of Participants With Non-serious AEs and SAEs-Part 3

Part 4 GSK3145095 + Anticancer Agent

Number of Participants With Non-serious AEs and SAEs-Part 4

Number of Participants With AEs by Severity Grades-Part 3

Number of Participants With AEs by Severity Grades-Part 4

Pharmacokinetic (PK) Population. The PK Population consisted of all participants from the All-Treated Population for whom a PK sample was obtained and analyzed. Study was terminated in Part-1 during first escalation cohort "GSK3145095 50 mg BID", hence subsequent escalation cohorts were not initiated.

Area Under the Plasma Drug Concentration Versus Time Curve (AUC[0-t]) Following Single Dose of GSK3145095 on Day 1-Part 1

PK Population: Data were not collected for this endpoint as study was terminated during Part 1. Subsequent Part 2 was not initiated.

AUC (0-t) Following Single Dose of GSK3145095 on Day 1-Part 2

PK Population: Study was terminated in Part-1 during first escalation cohort "GSK3145095 50 mg BID", hence subsequent escalation cohorts were not initiated.

Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Single Dose of GSK3145095 on Day 1-Part 1

AUC (0-tau) Following Single Dose of GSK3145095 on Day 1-Part 2

Maximum Observed Plasma Drug Concentration (Cmax) Following Single Dose of GSK3145095 on Day 1-Part 1

Cmax Following Single Dose of GSK3145095 on Day 1-Part 2

Minimum Observed Plasma Drug Concentration (Cmin) Following Single Dose of GSK3145095 on Day 1-Part 1

Cmin Following Single Dose of GSK3145095 on Day 1-Part 2

Time to Maximum Observed Plasma Drug Concentration (Tmax) Following Single Dose of GSK3145095 on Day 1-Part 1

Tmax Following Single Dose of GSK3145095 on Day 1-Part 2

Participants were to receive a single 400 mg dose of GSK3145095 orally on Day 1. From study Day 2, participants were to receive 800 mg dose of GSK3145095 given as 400 mg BID.

1-GSK3145095 200 mg BID

PK Population: Only those participants with data available at the specified data points were analyzed. Study was terminated in Part-1 during first escalation cohort "GSK3145095 50 mg BID", hence subsequent escalation cohorts were not initiated.

Clearance (CL/F) Following Single Dose of GSK3145095 on Day 1-Part 1

CL/F Following Single Dose of GSK3145095 on Day 1-Part 2

Participants were to receive a single 200 mg dose of GSK3145095 orally on Day 1. From study Day 2, participants were to receive 400 mg GSK3145095 given as 200 mg BID

Volume of Distribution (Vz/F) Following Single Dose of GSK3145095 on Day 1-Part 1

Vz/F Following Single Dose of GSK3145095 on Day 1-Part 2

Participants were to receive a single 800 mg dose of GSK3145095 orally on Day 1. From study Day 2, participants were to receive 1600 mg dose of GSK3145095 given as 800 mg BID

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
First-time-in-human (FTIH) Study of GSK3145095 Alone and in Combination With Other Anticancer Agents in Adults With Advanced Solid Tumors	NCT03681951	Neoplasms, Panc...	GSK3145095 Pembrolizumab	18 Years -	GlaxoSmithKline
Prospective Cohort Study of Immunotherapy Resistance in Metastatic Colorectal Cancer Patients With MSI	NCT06353854	Colorectal Canc... Microsatellite ...		18 Years -	Federation Francophone de Cancerologie Digestive
First-time-in-human (FTIH) Study of GSK3145095 Alone and in Combination With Other Anticancer Agents in Adults With Advanced Solid Tumors	NCT03681951	Neoplasms, Panc...	GSK3145095 Pembrolizumab	18 Years -	GlaxoSmithKline
Trial of Chidamide in Combination With Envafolimab in Patients With PD-1 Inhibitor Resistant Advanced NSCLC.	NCT05068427	Non Small Cell ...	Chidamide Envafolimab	18 Years -	Chipscreen Biosciences, Ltd.
Trial of Chidamide in Combination With Envafolimab in Patients With PD-1 Inhibitor Resistant Advanced NSCLC.	NCT05068427	Non Small Cell ...	Chidamide Envafolimab	18 Years -	Chipscreen Biosciences, Ltd.
Prospective Cohort Study of Immunotherapy Resistance in Metastatic Colorectal Cancer Patients With MSI	NCT06353854	Colorectal Canc... Microsatellite ...		18 Years -	Federation Francophone de Cancerologie Digestive

Spots Global Cancer Trial Database for immunotherapy resistance