NCT02528357

GSK3174998 Alone and With Pembrolizumab in Participants With Advanced Solid Tumors (ENGAGE-1)

Completed Phase 1 Results posted Last updated 18 May 2021

What this trial tests

Phase 1 trial testing GSK3174998 in Neoplasms in 141 participants. Completed in 29 April 2020.

Timeline

11 September 2015

Primary endpoint
29 April 2020

29 April 2020

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	141
Start date	11 September 2015
Primary completion	29 April 2020
Estimated completion	29 April 2020
Sites	8 locations across France, Canada, United States, Netherlands

Drugs / interventions tested

• GSK3174998 — full drug profile →
• Pembrolizumab (pembrolizumab) — full drug profile →

Conditions studied

• Neoplasms — all drugs for Neoplasms →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

18 and older, any sex, with Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) Primary · Up to maximum 39 weeks

An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE.

Any SAE

Group	Value	95% CI
Part 1: GSK3174998 0.003 mg/kg	1
Part 1: GSK3174998 0.01 mg/kg	0
Part 1: GSK3174998 0.03 mg/kg	3
Part 1: GSK3174998 0.1 mg/kg	7
Part 1: GSK3174998 0.3 mg/kg	2
Part 1: GSK3174998 1.0 mg/kg	1
Part 1: GSK3174998 3.0 mg/kg	2
Part 1: GSK3174998 10.0 mg/kg	1

Any non-SAE

Group	Value	95% CI
Part 1: GSK3174998 0.003 mg/kg	1
Part 1: GSK3174998 0.01 mg/kg	1
Part 1: GSK3174998 0.03 mg/kg	8
Part 1: GSK3174998 0.1 mg/kg	10
Part 1: GSK3174998 0.3 mg/kg	10
Part 1: GSK3174998 1.0 mg/kg	4
Part 1: GSK3174998 3.0 mg/kg	7
Part 1: GSK3174998 10.0 mg/kg	4

Part 2A: Number of Participants With Any SAE and Non-SAE Primary · Up to maximum 105 weeks

An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE.

Any SAE

Group	Value	95% CI
Part 2A: GSK3174998 0.003 mg/kg + Pembrolizumab 200 mg	1
Part 2A: GSK3174998 0.01 mg/kg + Pembrolizumab 200 mg	1
Part 2A: GSK3174998 0.03 mg/kg + Pembrolizumab 200 mg	6
Part 2A: GSK3174998 0.1 mg/kg + Pembrolizumab 200 mg	4
Part 2A: GSK3174998 0.3 mg/kg + Pembrolizumab 200 mg	4
Part 2A: GSK3174998 1.0 mg/kg + Pembrolizumab 200 mg	4
Part 2A: GSK3174998 3.0 mg/kg + Pembrolizumab 200 mg	2
Part 2A: GSK3174998 10.0 mg/kg + Pembrolizumab 200 mg	2

Any non-SAE

Group	Value	95% CI
Part 2A: GSK3174998 0.003 mg/kg + Pembrolizumab 200 mg	5
Part 2A: GSK3174998 0.01 mg/kg + Pembrolizumab 200 mg	5
Part 2A: GSK3174998 0.03 mg/kg + Pembrolizumab 200 mg	10
Part 2A: GSK3174998 0.1 mg/kg + Pembrolizumab 200 mg	12
Part 2A: GSK3174998 0.3 mg/kg + Pembrolizumab 200 mg	13
Part 2A: GSK3174998 1.0 mg/kg + Pembrolizumab 200 mg	12
Part 2A: GSK3174998 3.0 mg/kg + Pembrolizumab 200 mg	12
Part 2A: GSK3174998 10.0 mg/kg + Pembrolizumab 200 mg	4

Part 2B: Number of Participants With Any SAE and Non-SAE Primary · Up to maximum 33 weeks

An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE.

Any SAE

Group	Value	95% CI
Part 2B: Melanoma Cohort	1
Part 2B: Soft Tissue Sarcoma Cohort	2
Part 2B: NSCLC Cohort	1

Any non-SAE

Group	Value	95% CI
Part 2B: Melanoma Cohort	9
Part 2B: Soft Tissue Sarcoma Cohort	8
Part 2B: NSCLC Cohort	4

Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) Primary · 28 days

An adverse event was considered as DLT if it was considered by the investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment, occurred within the first 28 days of the treatment, and met 1 of the following criteria: Hematologic: Febrile neutropenia, Grade4 neutropenia of \>7days requiring Granulocyte colony-stimulating factor (G-CSF), Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding as described in National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE ve

Group	Value	95% CI
Part 1: GSK3174998 0.003 mg/kg	0
Part 1: GSK3174998 0.01 mg/kg	0
Part 1: GSK3174998 0.03 mg/kg	0
Part 1: GSK3174998 0.1 mg/kg	0
Part 1: GSK3174998 0.3 mg/kg	0
Part 1: GSK3174998 1.0 mg/kg	0
Part 1: GSK3174998 3.0 mg/kg	0
Part 1: GSK3174998 10.0 mg/kg	0

Part 2A: Number of Participants With DLTs Primary · 28 days

An adverse event was considered as DLT if it was considered by the investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment, occurred within the first 28 days of the treatment, and met 1 of the following criteria: Hematologic: Febrile neutropenia, Grade4 neutropenia of \>7days requiring Granulocyte colony-stimulating factor (G-CSF), Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding as described in National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE ve

Group	Value	95% CI
Part 2A: GSK3174998 0.003 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 0.01 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 0.03 mg/kg + Pembrolizumab 200 mg	1
Part 2A: GSK3174998 0.1 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 0.3 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 1.0 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 3.0 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 10.0 mg/kg + Pembrolizumab 200 mg	1

Part 2B: Number of Participants With DLTs Primary · 28 days

An adverse event was considered as DLT if it was considered by the investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment, occurred within the first 28 days of the treatment, and met 1 of the following criteria: Hematologic: Febrile neutropenia, Grade4 neutropenia of \>7days requiring Granulocyte colony-stimulating factor (G-CSF), Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding as described in National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE ve

Group	Value	95% CI
Part 2B: Melanoma Cohort	0
Part 2B: Soft Tissue Sarcoma Cohort	0
Part 2B: NSCLC Cohort	0

Part 1: Number of Participants With Any Adverse Event Leading to Withdrawal (AELD) From the Study Primary · Up to maximum 39 weeks

An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any adverse event leading to withdrawal from the study is presented.

Group	Value	95% CI
Part 1: GSK3174998 0.003 mg/kg	0
Part 1: GSK3174998 0.01 mg/kg	0
Part 1: GSK3174998 0.03 mg/kg	0
Part 1: GSK3174998 0.1 mg/kg	0
Part 1: GSK3174998 0.3 mg/kg	0
Part 1: GSK3174998 1.0 mg/kg	0
Part 1: GSK3174998 3.0 mg/kg	0
Part 1: GSK3174998 10.0 mg/kg	0

Part 2A: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study Primary · Up to maximum 105 weeks

An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any adverse event leading to withdrawal from the study is presented.

Group	Value	95% CI
Part 2A: GSK3174998 0.003 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 0.01 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 0.03 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 0.1 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 0.3 mg/kg + Pembrolizumab 200 mg	1
Part 2A: GSK3174998 1.0 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 3.0 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 10.0 mg/kg + Pembrolizumab 200 mg	0

Part 2B: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study Primary · Up to maximum 33 weeks

An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any adverse event leading to withdrawal from the study is presented.

Group	Value	95% CI
Part 2B: Melanoma Cohort	0
Part 2B: Soft Tissue Sarcoma Cohort	0
Part 2B: NSCLC Cohort	0

Part 1: Number of Participants With Dose Reductions or Delay Primary · Up to maximum 39 weeks

Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented.

Dose reduction

Group	Value	95% CI
Part 1: GSK3174998 0.003 mg/kg	0
Part 1: GSK3174998 0.01 mg/kg	0
Part 1: GSK3174998 0.03 mg/kg	0
Part 1: GSK3174998 0.1 mg/kg	0
Part 1: GSK3174998 0.3 mg/kg	0
Part 1: GSK3174998 1.0 mg/kg	0
Part 1: GSK3174998 3.0 mg/kg	0
Part 1: GSK3174998 10.0 mg/kg	0

Dose delay

Group	Value	95% CI
Part 1: GSK3174998 0.003 mg/kg	0
Part 1: GSK3174998 0.01 mg/kg	0
Part 1: GSK3174998 0.03 mg/kg	0
Part 1: GSK3174998 0.1 mg/kg	1
Part 1: GSK3174998 0.3 mg/kg	0
Part 1: GSK3174998 1.0 mg/kg	1
Part 1: GSK3174998 3.0 mg/kg	0
Part 1: GSK3174998 10.0 mg/kg	0

Part 2A: Number of Participants With Dose Reductions or Delay Primary · Up to maximum 105 weeks

Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented.

Dose reduction

Group	Value	95% CI
Part 2A: GSK3174998 0.003 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 0.01 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 0.03 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 0.1 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 0.3 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 1.0 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 3.0 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 10.0 mg/kg + Pembrolizumab 200 mg	0

Dose delay

Group	Value	95% CI
Part 2A: GSK3174998 0.003 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 0.01 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 0.03 mg/kg + Pembrolizumab 200 mg	1
Part 2A: GSK3174998 0.1 mg/kg + Pembrolizumab 200 mg	1
Part 2A: GSK3174998 0.3 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 1.0 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 3.0 mg/kg + Pembrolizumab 200 mg	0
Part 2A: GSK3174998 10.0 mg/kg + Pembrolizumab 200 mg	0

Part 2B: Number of Participants With Dose Reductions or Delay Primary · Up to maximum 33 weeks

Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented.

Dose reduction

Group	Value	95% CI
Part 2B: Melanoma Cohort	0
Part 2B: Soft Tissue Sarcoma Cohort	0
Part 2B: NSCLC Cohort	0

Dose delay

Group	Value	95% CI
Part 2B: Melanoma Cohort	0
Part 2B: Soft Tissue Sarcoma Cohort	0
Part 2B: NSCLC Cohort	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 39 weeks in Part 1; Up to 105 weeks in Part 2A; Up to 33 weeks in Part 2B. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part 1: GSK3174998 0.003 mg/kg

Serious: 1/1 (100%)

Deaths: 1/1

Part 1: GSK3174998 0.01 mg/kg

Serious: 0/1 (0%)

Deaths: 0/1

Part 1: GSK3174998 0.03 mg/kg

Serious: 3/8 (38%)

Deaths: 6/8

Part 1: GSK3174998 0.1 mg/kg

Serious: 7/10 (70%)

Deaths: 9/10

Part 1: GSK3174998 0.3 mg/kg

Serious: 2/10 (20%)

Deaths: 6/10

Part 1: GSK3174998 1.0 mg/kg

Serious: 1/4 (25%)

Deaths: 2/4

Part 1: GSK3174998 3.0 mg/kg

Serious: 2/7 (29%)

Deaths: 5/7

Part 1: GSK3174998 10.0 mg/kg

Serious: 1/4 (25%)

Deaths: 2/4

Part 2A: GSK3174998 0.003 mg/kg + Pembrolizumab 200 mg

Serious: 1/5 (20%)

Deaths: 4/5

Part 2A: GSK3174998 0.01 mg/kg + Pembrolizumab 200 mg

Serious: 1/5 (20%)

Deaths: 4/5

Part 2A: GSK3174998 0.03 mg/kg + Pembrolizumab 200 mg

Serious: 6/10 (60%)

Deaths: 7/10

Part 2A: GSK3174998 0.1 mg/kg + Pembrolizumab 200 mg

Serious: 4/12 (33%)

Deaths: 9/12

Part 2A: GSK3174998 0.3 mg/kg + Pembrolizumab 200 mg

Serious: 4/14 (29%)

Deaths: 9/14

Part 2A: GSK3174998 1.0 mg/kg + Pembrolizumab 200 mg

Serious: 4/12 (33%)

Deaths: 6/12

Part 2A: GSK3174998 3.0 mg/kg + Pembrolizumab 200 mg

Serious: 2/12 (17%)

Deaths: 5/12

Part 2A: GSK3174998 10.0 mg/kg + Pembrolizumab 200 mg

Serious: 2/4 (50%)

Deaths: 4/4

Part 2B: Melanoma Cohort

Serious: 1/9 (11%)

Deaths: 6/9

Part 2B: Soft Tissue Sarcoma Cohort

Serious: 2/8 (25%)

Deaths: 4/8

Part 2B: NSCLC Cohort

Serious: 1/5 (20%)

Deaths: 2/5

Serious adverse events (53 terms)

Reaction	System	Part 1: GSK3174998 0.003 m…	Part 1: GSK3174998 0.01 mg…	Part 1: GSK3174998 0.03 mg…	Part 1: GSK3174998 0.1 mg/kg	Part 1: GSK3174998 0.3 mg/kg	Part 1: GSK3174998 1.0 mg/kg	Part 1: GSK3174998 3.0 mg/kg	Part 1: GSK3174998 10.0 mg…	Part 2A: GSK3174998 0.003 …	Part 2A: GSK3174998 0.01 m…	Part 2A: GSK3174998 0.03 m…	Part 2A: GSK3174998 0.1 mg…	Part 2A: GSK3174998 0.3 mg…	Part 2A: GSK3174998 1.0 mg…	Part 2A: GSK3174998 3.0 mg…	Part 2A: GSK3174998 10.0 m…	Part 2B: Melanoma Cohort	Part 2B: Soft Tissue Sarco…	Part 2B: NSCLC Cohort
Pneumonia	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Myocarditis	Cardiac disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pituitary haemorrhage	Endocrine disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Colonic fistula	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Large intestinal obstruction	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Malaise	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Non-cardiac chest pain	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Bile duct stenosis	Hepatobiliary disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Device related infection	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Urosepsis	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dislocation of vertebra	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hip fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Spinal compression fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Blood creatine phosphokinase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

Other adverse events (250 terms — click to expand)

Reaction	System	Part 1: GSK3174998 0.003 m…	Part 1: GSK3174998 0.01 mg…	Part 1: GSK3174998 0.03 mg…	Part 1: GSK3174998 0.1 mg/kg	Part 1: GSK3174998 0.3 mg/kg	Part 1: GSK3174998 1.0 mg/kg	Part 1: GSK3174998 3.0 mg/kg	Part 1: GSK3174998 10.0 mg…	Part 2A: GSK3174998 0.003 …	Part 2A: GSK3174998 0.01 m…	Part 2A: GSK3174998 0.03 m…	Part 2A: GSK3174998 0.1 mg…	Part 2A: GSK3174998 0.3 mg…	Part 2A: GSK3174998 1.0 mg…	Part 2A: GSK3174998 3.0 mg…	Part 2A: GSK3174998 10.0 m…	Part 2B: Melanoma Cohort	Part 2B: Soft Tissue Sarco…	Part 2B: NSCLC Cohort
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Middle ear inflammation	Ear and labyrinth disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypothyroidism	Endocrine disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Chills	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Influenza like illness	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Localised oedema	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Blood creatinine increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Lipase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hyperkalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Neck pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

Most-reported serious reactions: Pneumonia, Asthenia, Fatigue, Dyspnoea, Anaemia, Myocarditis, Pituitary haemorrhage, Abdominal pain.

Data from ClinicalTrials.gov NCT02528357 adverse events section.

Sponsor's own description

This is a first time in human (FTIH), open-label, non-randomized, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary clinical activity of GSK3174998 administered intravenously to participants with selected advanced or recurrent solid tumors. This dose-escalation study will assess the safety, activity of GSK3174998 as monotherapy (Part 1), in combination with pembrolizumab (Part 2), and potentially in combination with additional therapies.

The study will be conducted in 2 parts, each part consisting of starting with a dose-escalation phase followed by a cohort expansion phase. GSK3174998 will first be evaluated as monotherapy in escalating doses. Once a dose of GSK3174998 has been identified that is both tolerable and demonstrates pharmacodynamic activity, enrollment of Part 2 may begin. In Part 2, escalating doses of GSK3174998 will be evaluated with fixed doses of pembrolizumab.

The maximum duration of treatment with GSK3174998 and pembrolizumab will be approximately 2 years or 35 cycles, whichever comes first. The follow-up period for safety assessments will be a minimum of 3 months from the date of the last dose. The post-treatment follow-up period will include disease assessments every 12 weeks until documented progressive disease (PD). Approximately 141 participants with selected advanced or recurrent solid tumors will be enrolled.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Immunotherapy in colorectal cancer: rationale, challenges and potential.
   Ganesh K, Stadler ZK, Cercek A, Mendelsohn RB, et al · · 2019 · cited 1407× · PMID 30886395 · DOI 10.1038/s41575-019-0126-x
2. Next generation of immune checkpoint therapy in cancer: new developments and challenges.
   Marin-Acevedo JA, Dholaria B, Soyano AE, Knutson KL, et al · · 2018 · cited 582× · PMID 29544515 · DOI 10.1186/s13045-018-0582-8
3. Signal pathways of melanoma and targeted therapy.
   Guo W, Wang H, Li C. · · 2021 · cited 251× · PMID 34924562 · DOI 10.1038/s41392-021-00827-6
4. Timing of PD-1 Blockade Is Critical to Effective Combination Immunotherapy with Anti-OX40.
   Messenheimer DJ, Jensen SM, Afentoulis ME, Wegmann KW, et al · · 2017 · cited 249× · PMID 28855348 · DOI 10.1158/1078-0432.ccr-16-2677
5. Biomarkers for immunotherapy in bladder cancer: a moving target.
   Aggen DH, Drake CG. · · 2017 · cited 133× · PMID 29157296 · DOI 10.1186/s40425-017-0299-1
6. Targeting Negative and Positive Immune Checkpoints with Monoclonal Antibodies in Therapy of Cancer.
   Marhelava K, Pilch Z, Bajor M, Graczyk-Jarzynka A, et al · · 2019 · cited 100× · PMID 31717326 · DOI 10.3390/cancers11111756
7. T-cell agonists in cancer immunotherapy.
   Choi Y, Shi Y, Haymaker CL, Naing A, et al · · 2020 · cited 90× · PMID 33020242 · DOI 10.1136/jitc-2020-000966
8. Immune checkpoint inhibitors for urothelial carcinoma.
   Kim HS, Seo HK. · · 2018 · cited 84× · PMID 30182073 · DOI 10.4111/icu.2018.59.5.285