NeoplasmsPhase 1NCT02528357

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

A Phase 1 study testing GSK3174998 and Pembrolizumab in people with Neoplasms, run by GlaxoSmithKline at 8 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Neoplasms
What is being tested?: GSK3174998 and Pembrolizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 141 participants
Where: 8 sitesin 4 countries
Study dates: 11 Sep 2015to 29 Apr 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Provide signed, written informed consent.
Male and female participants, age >=18 years (at the time consent is obtained).
Histological documentation of locally advanced, recurrent or metastatic solid malignancy that has progressed after standard therapy appropriate for the specific tumor type, or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate. Participants should not have received more than 5 prior lines of therapy for advanced disease including both standards of care and investigational therapies. Participants whose cancers harbor molecular alterations for which targeted therapy is standard of care should have received health authority approved appropriate targeted therapy for their tumor types before enrollment.
Participants with the following solid tumors are eligible for screening: Non-small cell lung cancer (NSCLC), Squamous cell carcinoma of the head and neck (SCCHN), Renal cell carcinoma (RCC), melanoma, bladder, Soft Tissue Sarcoma (STS), Triple-negative breast cancer (TNBC), and Colorectal carcinoma displaying high microsatellite instability (MSI CRC). In Part 2B (Cohort Expansion), specific subgroups of the above solid tumors will be studied. These subgroups may be defined by specific lines of treatment, types of prior treatment, histological subtypes, and may be enriched for selected biomarkers or participant characteristics. Populations to be studied in Amendment 3 include but are not limited to the following. Enrolment of additional populations will be communicated in writing: Participants with dedifferentiated liposarcoma who have not received prior treatment with a Programmed death ligand 1 (PD-L1) inhibitor; Participants with melanoma who have received a prior PD-L1 inhibitor, had a CR, PR or SD and subsequently progressed while on PD-L1 therapy. Participants who have received prior treatment with a PD-L1 inhibitor must have documented disease progression as defined by meeting all of the following criteria: Has received at least 2 doses of an approved PD-L1 inhibitor; has demonstrated disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The initial evidence of disease progression is to be confirmed by a second assessment no less than four weeks from the date of the first documented PD , in the absence of rapid clinical progression; Progressive disease has been documented within 18 weeks from the last dose of the PD-L1 inhibitor.
In Parts 1A and 2A, a biopsy of the tumor tissue obtained at anytime from the initial diagnosis to study entry. Although a fresh biopsy obtained during screening is preferred, archival tumor specimen is acceptable if it is not feasible to obtain a fresh biopsy.
Participants enrolled in Part 1A or Part 2A Pharmacodynamic Cohorts or in Part 2B of the study must provide a fresh biopsy of a tumor lesion not previously irradiated during the screening period and must agree to provide at least one additional on-treatment biopsy. In addition, an archived tumor tissue should be submitted for Participants in Part 2B, if available. The criterion for collection of fresh biopsies may be waived once GlaxoSmithKline (GSK)has determined an appropriate number of viable tissue samples have been analyzed For Part 1B and Part 2B, any archival tumor specimen must have been obtained within 3 months of starting study drug.

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Measurable disease as per RECIST v1.1
Palpable lesions that are not measurable by radiologic or photographic evaluations may not be utilized as the only measurable lesion.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
Life expectancy of at least 12 weeks.
Adequate organ function as defined by System Laboratory Values; Hematologic (Absolute neutrophil count [ANC] >=1.5x10^9/ liter [L], Lymphocyte count >=800/cubic millimeter [mm^3], Hemoglobin >=9 grams/deciliter [g/dL], Platelets >=100x10^9/L), Hepatic (Total bilirubin <=1.5x upper limit of normal [ULN] [For participants with Gilbert's Syndrome, only if direct bilirubin <=35 percent (%), <=3.0xULN], for Part 1A and 2A: alanine aminotransferase [ALT] <=1.5xULN), Part 2B: ALT <=2.5xULN; Renal (Serum Creatinine <=1.5xULN OR Calculated creatinine clearance [CrCl >50 mL/min ) and Endocrine (Thyroid stimulating hormone [TSH]) within normal limits. If TSH is not within normal limits at baseline, the participant may still be eligible if total triiodothyronine (T3) or free T3 and free thyroxine (T4) are within the normal limits.
QT duration corrected for heart rate by Fridericia's formula (QTcF) <450 milliseconds (msec) or <480 msec for participants with bundle branch block.
In France, a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Female participant: is eligible to participate if she is not pregnant (as confirmed by a negative serum beta-human chorionic gonadotrophin [beta-hCG] test), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion ; Hysterectomy; Documented Bilateral Oophorectomy.
Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
Reproductive potential and agrees to follow one of the options listed below in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until 120 days after the last dose of study medication and completion of the follow-up visit. GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP).
This list does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for participants who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis: Contraceptive subdermal implant with a <1% rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system with a <1% rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone; Injectable progestogen; Contraceptive vaginal ring; Percutaneous contraceptive patches; Male partner sterilization with documentation of azoospermia prior to the female participant's entry into the study, and this male is the sole partner for that participant. These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that participants understand how to properly use these methods of contraception.
Male Participants with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until 120 days after the last dose of study medication: Vasectomy with documentation of azoospermia; Male condom plus partner use of one of the contraceptive options below; Contraceptive subdermal implant with a <1% rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system with a <1% rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone Injectable progestogen; Contraceptive vaginal ring; Percutaneous contraceptive patches.
These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that participants understand how to properly use these methods of contraception.

Who cannot join

Prior treatment with the following agents (from last dose of prior treatment to first dose of GSK3174998): Tumor necrosis factor receptor (TNFR) agonists, including OX40, CD27, CD137 (4-1BB), CD357 (GITR): at any time; Checkpoint inhibitors, including Programmed death receptor-1 (PD-1),
1, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors: within 4 weeks; other anticancer therapy, including chemotherapy, targeted therapy, and biological therapy: within 4 weeks or 5 half lives of the drug, whichever is shorter. Prior radiation therapy is permissible if at least one unirradiated measurable lesion is available for assessment via RECIST version 1.1. A wash out of at least two weeks before start of study drug for palliative radiation to the extremities for osseous bone metastases and 4 weeks for radiation to the chest, brain, or visceral organs is required; Investigational therapy: if the participant has participated in a clinical trial and has received an investigational product: within 30 days or 5 half-lives of the investigational product (whichever is shorter). At least 14 days must have passed between the last dose of prior investigational agent and the first dose of study drug.
Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.
Toxicity from previous treatment: Participants with >=Grade 3 toxicity related to prior immunotherapy leading to study treatment discontinuation are not eligible; participants whose toxicity related to prior treatment has not resolved to <=Grade 1 (except alopecia, hearing loss, grade <=2 neuropathy or endocrinopathy managed with replacement therapy) are not eligible.
Malignancy other than disease under study, except as noted below: any other malignancy from which the participant has been disease-free for more than 2 years and, in the opinion of the principal investigators and GSK Medical Monitor, will not affect the evaluation of the effects of this clinical trial treatment on currently targeted malignancy, can be included in this clinical trial.
Central nervous system (CNS) metastases, with the following exception: Participants who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids for 2 weeks prior to first dose of study drug.

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Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GMCSF], recombinant erythropoietin) within 2 weeks before the first dose of study drug.
Major surgery <=4 weeks before the first dose of study treatment. Participants must have also fully recovered from any surgery (major or minor) and/or its complications before initiating study treatment.
Active autoimmune disease that has required systemic treatment within the last 2 years (that is with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (example [e.g.], thyroxine or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Concurrent medical condition requiring the use of systemic immunosuppressive medications within 28 days before the first dose of study treatment. Physiologic doses of corticosteroids for treatment of endocrinopathies or steroids with minimal systemic absorption, including topical, inhaled, or intranasal corticosteroids may be continued if the participant is on a stable dose.
Active infection, known human immunodeficiency virus infection, or positive test for hepatitis B surface antigen or hepatitis C.
Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease per investigator assessment).
Known, current drug or alcohol abuse.
Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction.
Receipt of any live vaccine within 4 weeks.
Recent history of allergen desensitization therapy within 4 weeks of starting study Treatment.
History of severe hypersensitivity to other mAbs.
History or evidence of cardiovascular risk including any of the following: Recent (within the past 6 months) history of serious uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities including second degree (Type II) or third degree atrioventricular block; Documented cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting, or bypass grafting within the past 6 months before enrollment; documented congestive heart failure (Class II, III, or IV) as defined by the New York Heart Association functional classification system; recent (within the past 6 months) history of symptomatic pericarditis Current or history of idiopathic pulmonary fibrosis, interstitial lung disease, or organizing pneumonia.
History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural effusions.
Any serious and/or unstable pre-existing medical, psychiatric disorder, or other condition that could interfere with the participant's safety, obtaining informed consent, or compliance to the study procedures.
Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective Institutional Review Board (IRB) approval (by chair or designee) is given allowing exception to this criterion for a specific participant.
History of severe hypersensitivity (>=Grade 3) to pembrolizumab and/or any of its excipients.

Trial locations and contacts

8 sites in 4 countries.

Country

City, postcode or hospital

8 sites in 4 countries

United States5 sites

GSK Investigational Site
Boston, Massachusetts, 02215
GSK Investigational Site
Houston, Texas, 77030
GSK Investigational Site
Nashville, Tennessee, 37203
GSK Investigational Site
New York, New York, 10016
GSK Investigational Site
New York, New York, 10065

Other trials in United States

Canada1 site

GSK Investigational Site
Toronto, Ontario, M5G 2M9

Other trials in Canada

France1 site

GSK Investigational Site
Villejuif, 94805

Other trials in France

Netherlands1 site

GSK Investigational Site
Amsterdam, 1066 CX

Other trials in Netherlands

About this study

Official title: A Phase I, Open-Label Study of GSK3174998 Administered Alone and in Combination With Anticancer Agents Including Pembrolizumab in Subjects With Selected Advanced Solid Tumors

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.

Conditions: Neoplasms
Being tested: GSK3174998, Pembrolizumab
Keywords: GSK3174998, Non-small Cell Lung Cancer (NSCLC), OX40, Pembrolizumab, Monoclonal Antibody (mAb), Selected Advanced Solid Tumors
Medical subject headings: Neoplasms, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK3174998Drug
Lyophilized powder 40 mg reconstituted to get a dose range of 0.003 to <=10 mg/kg to be given as IV infusion for 30 minutes (min), Q3W
PembrolizumabDrug
Pembrolizumab as 100 mg/4 milliliter (mL) solution (dose: 200 mg) to be given as IV infusion for 30 min, Q3W

Study groups in NCT02528357
Study group	Role	What they receive
Part 1A: GSK3174998 Monotherapy- Dose escalation	Experimental	Participants will receive GSK3174998 intravenously (IV) (dose range 0.003 to 10.0 milligram per kilogram [mg/kg]) every 3 weeks (Q3W) for up to 2 years or 35 cycles, whichever comes first. Receives: Drug: GSK3174998
Part 2A: GSK3174998+ pembrolizumab - Dose escalation	Experimental	Participants will receive GSK3174998 IV (dose range 0.003 to 10.0 mg/kg) Q3W for up to 2 years or 35 cycles, whichever comes first + Pembrolizumab 200 mg IV Q3W for up to 2 years or 35 cycles, whichever comes first. Receives: Drug: GSK3174998; Drug: Pembrolizumab
Part 2B: GSK3174998+ pembrolizumab - Cohort expansion	Experimental	Participants will receive GSK3174998 IV (at one dose level shown to be tolerable in dose escalation of part 2A) Q3W for up to 2 years or 35 cycles, whichever comes first + Pembrolizumab 200 mg IV Q3W for 2 years or 35 cycles, whichever comes first. Receives: Drug: GSK3174998; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE)
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.
Measured: Up to maximum 39 weeks
Part 2A: Number of Participants With Any SAE and Non-SAE
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.
Measured: Up to maximum 105 weeks
Part 2B: Number of Participants With Any SAE and Non-SAE
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.
Measured: Up to maximum 33 weeks
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
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 version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of >=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT.
Measured: 28 days
Part 2A: Number of Participants With DLTs
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 version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of >=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT.
Measured: 28 days
Part 2B: Number of Participants With DLTs
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 version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of >=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT.
Measured: 28 days
Part 1: Number of Participants With Any Adverse Event Leading to Withdrawal (AELD) From the Study
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.
Measured: Up to maximum 39 weeks
Part 2A: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study
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.
Measured: Up to maximum 105 weeks
Part 2B: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study
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.
Measured: Up to maximum 33 weeks
Part 1: Number of Participants With Dose Reductions or Delay
Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented.
Measured: Up to maximum 39 weeks
Part 2A: Number of Participants With Dose Reductions or Delay
Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented.
Measured: Up to maximum 105 weeks
Part 2B: Number of Participants With Dose Reductions or Delay
Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented.
Measured: Up to maximum 33 weeks
Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters
Blood samples were collected for the analysis of following hematology parameters: hemoglobin (Hb), leukocyte count (leuko.), lymphocyte count (Lymph.), neutrophil count (Neutro.) and platelet count (PC). The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Measured: Baseline (Day 1) and up to maximum 39 weeks
Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters
Blood samples were collected for the analysis of following hematology parameters: Hb, leuko., Lymph., Neutro. and PC. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Measured: Baseline (Day 1) and up to maximum 105 weeks
Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters
Blood samples were collected for the analysis of following hematology parameters: Hb, leuko., Lymph., Neutro. and PC. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Measured: Baseline (Day 1) and up to maximum 33 weeks
Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters
Blood samples were collected for the analysis of following liver function laboratory parameters: alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Measured: Baseline (Day 1) and up to maximum 39 weeks
Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters
Blood samples were collected for the analysis of following liver function laboratory parameters: ALT, ALP, AST and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Measured: Baseline (Day 1) and up to maximum 105 weeks
Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters
Blood samples were collected for the analysis of following liver function laboratory parameters: ALT, ALP, AST and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Measured: Baseline (Day 1) and up to maximum 33 weeks
Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: <120 millimeter mercury (mmHg); Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: >=160 mmHg. For DBP: Grade 0: <80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: >=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Measured: Baseline (Day 1) and up to maximum 39 weeks
Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP
SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: <120 mmHg; Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: >=160 mmHg. For DBP: Grade 0: <80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: >=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Measured: Baseline (Day 1) and up to maximum 105 weeks
Part 2B: Number of Participants With Any Grade Change From Baseline in SBP and DBP
SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: <120 mmHg; Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: >=160 mmHg. For DBP: Grade 0: <80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: >=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Measured: Baseline (Day 1) and up to maximum 33 weeks
Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR)
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: <60 beats per minute [bpm]', normal HR: 60 to 100 bpm and high HR: >100 bpm. If values were unchanged (example: increase to >100 bpm to increase to >100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Measured: Baseline (Day 1) and up to maximum 39 weeks
Part 2A: Number of Participants With Worst Case Change From Baseline in HR
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: <60 bpm', normal HR: 60 to 100 bpm and high HR: >100 bpm. If values were unchanged (example: increase to >100 bpm to increase to >100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Measured: Baseline (Day 1) and up to maximum 105 weeks
Part 2B: Number of Participants With Worst Case Change From Baseline in HR
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: <60 bpm', normal HR: 60 to 100 bpm and high HR: >100 bpm. If values were unchanged (example: increase to >100 bpm to increase to >100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Measured: Baseline (Day 1) and up to maximum 33 weeks
Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: <=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: >=38 degrees Celsius. If values were unchanged (example: increase to >=38 degrees Celsius to increase to >=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Measured: Baseline (Day 1) and up to maximum 39 weeks
Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: <=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: >=38 degrees Celsius. If values were unchanged (example: increase to >=38 degrees Celsius to increase to >=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Measured: Baseline (Day 1) and up to maximum 105 weeks
Part 2B: Number of Participants With Worst Case Change From Baseline in Body Temperature
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: <=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: >=38 degrees Celsius. If values were unchanged (example: increase to >=38 degrees Celsius to increase to >=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Measured: Baseline (Day 1) and up to maximum 33 weeks
Part 1: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant Electrocardiogram (ECG) Findings
A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented.
Measured: Up to maximum 39 weeks
Part 2A: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings
A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented.
Measured: Up to maximum 105 weeks
Part 2B: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings
A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented.
Measured: Up to maximum 33 weeks

Secondary outcomes (28)

Part 1: Objective Response Rate (ORR)
ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or a partial response (PR) as the Best Overall Response (BOR), as assessed by the investigator per Response Evaluation Criteria In Solid Tumors (RECIST) Version (v) 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30 percent (%) decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart.
Measured: Up to maximum 39 weeks
Part 2A: Objective Response Rate (ORR)
ORR is defined as the percentage of participants achieving a confirmed CR or PR as the BOR, as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart.
Measured: Up to maximum 105 weeks
Part 2B: Objective Response Rate (ORR)
ORR is defined as the percentage of participants achieving a confirmed CR or PR as the BOR, as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart.
Measured: Up to maximum 33 weeks
Part 1: Disease Control Rate (DCR)
DCR is defined as the percentage of participants with a confirmed CR or PR at any time, plus stable disease (SD) >=12 weeks as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. SD: 30% decrease in tumor burden compared with Baseline cannot be established nor 20% increase compared with nadir.
Measured: Up to maximum 39 weeks
Part 2A: Disease Control Rate (DCR)
DCR is defined as the percentage of participants with a confirmed CR or PR at any time, plus SD >=12 weeks as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. SD: 30% decrease in tumor burden compared with Baseline cannot be established nor 20% increase compared with nadir.
Measured: Up to maximum 105 weeks
Part 2B: Disease Control Rate (DCR)
DCR is defined as the percentage of participants with a confirmed CR or PR at any time, plus SD >=12 weeks as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. SD: 30% decrease in tumor burden compared with Baseline cannot be established nor 20% increase compared with nadir.
Measured: Up to maximum 33 weeks
Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points
Blood samples for pharmacokinetic (PK) analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion (EOI); anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion.
Measured: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion
Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion (EOI); anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion.
Measured: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion
Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion (EOI); anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion.
Measured: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion
Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.
Measured: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Part 2A: AUC(0-tau) of GSK3174998
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.
Measured: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Part 2B: AUC(0-tau) of GSK3174998
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.
Measured: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.
Measured: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Part 2A: Cmax and Cmin of GSK3174998
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.
Measured: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Part 2B: Cmax and Cmin of GSK3174998
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.
Measured: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points
Blood samples for PK analysis of pembrolizumab were collected on Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion (EOPI); anytime on Days 8,15; Pre-dose on Days 22, 64, 106.
Measured: Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22, 64, 106
Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points
Blood samples for PK analysis of pembrolizumab were collected on Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15; Pre-dose on Days 22, 64, 106.
Measured: Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22, 64, 106
Part 2A: AUC(0-tau) of Pembrolizumab
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.
Measured: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days)
Part 2B: AUC(0-tau) of Pembrolizumab
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.
Measured: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days)
Part 2A: Cmax of Pembrolizumab
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.
Measured: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days)
Part 2B: Cmax of Pembrolizumab
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.
Measured: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days)
Part 2A: Cmin of Pembrolizumab
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.
Measured: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days)
Part 2B: Cmin of Pembrolizumab
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.
Measured: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days)
Part 1: Number of Participants With Positive Antidrug Antibodies (ADAs) Against GSK3174998
Serum samples were collected for the determination of anti-GSK3174998 antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a GSK3174998 bridging style ADA assay with a bio-analytically determined cut-point determined during assay validation. Samples taken after dosing with GSK3174998 that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-GSK3174998 antibodies results at any visit during the study have been presented.
Measured: Up to maximum 39 weeks
Part 2A: Number of Participants With Positive ADAs Against GSK3174998
Serum samples were collected for the determination of anti-GSK3174998 antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a GSK3174998 bridging style ADA assay with a bio-analytically determined cut-point (determined during assay validation). Samples taken after dosing with GSK3174998 that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-GSK3174998 antibodies results at any visit during the study have been presented.
Measured: Up to maximum 105 weeks
Part 2B: Number of Participants With Positive ADAs Against GSK3174998
Serum samples were collected for the determination of anti-GSK3174998 antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a GSK3174998 bridging style ADA assay with a bio-analytically determined cut-point (determined during assay validation). Samples taken after dosing with GSK3174998 that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-GSK3174998 antibodies results at any visit during the study have been presented.
Measured: Up to maximum 33 weeks
Part 2A: Number of Participants With Positive ADAs Against Pembrolizumab
Serum samples were collected for the determination of anti-pembrolizumab antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a pembrolizumab bridging style ADA assay with a bio-analytically determined cut-point (determined during assay validation). Samples taken after dosing with pembrolizumab that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-pembrolizumab antibodies results at any visit during the study have been presented.
Measured: Up to maximum 105 weeks
Part 2B: Number of Participants With Positive ADAs Against Pembrolizumab
Serum samples were planned to be collected for the determination of anti-pembrolizumab antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps.
Measured: Up to maximum 33 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Sep 201529 Apr 2020

First posted19 Aug 2015 (estimated)
Study start11 Sep 2015
Primary completion29 Apr 2020
Study completion29 Apr 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for NeoplasmsStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 141 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02528357
Sponsor's protocol ID: 201212
Other IDs: 2015-000152-14, 2015
Status last verified: Apr 2021
First submitted: 17 Aug 2015
Last updated: 18 May 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated device: No
Individual data sharing: Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Publications

Postel-Vinay S, Lam VK, Ros W, Bauer TM, Hansen AR, Cho DC, Stephen Hodi F, Schellens JHM, Litton JK, Aspeslagh S, Autio KA, Opdam FL, McKean M, Somaiah N, Champiat S, Altan M, Spreafico A, Rahma O, Paul EM, Ahlers CM, Zhou H, Struemper H, Gorman SA, Watmuff M, Yablonski KM, Yanamandra N, Chisamore MJ, Schmidt EV, Hoos A, Marabelle A, Weber JS, Heymach JV. First-in-human phase I study of the OX40 agonist GSK3174998 with or without pembrolizumab in patients with selected advanced solid tumors (ENGAGE-1). J Immunother Cancer. 2023 Mar;11(3):e005301. doi: 10.1136/jitc-2022-005301.
PubMed 36927527

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Study at a glance

From the registry record, last updated by the sponsor on 18 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I, Open-Label Study of GSK3174998 Administered Alone and in Combination With Anticancer Agents Including Pembrolizumab in Subjects With Selected Advanced Solid Tumors
ClinicalTrials.gov ID: NCT02528357
Acronym / sponsor ID: 201212
Conditions: Neoplasms
Keywords: GSK3174998, Non-small Cell Lung Cancer (NSCLC), OX40, Pembrolizumab, Monoclonal Antibody (mAb), Selected Advanced Solid Tumors
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 141 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Collaborators: Merck Sharp & Dohme LLC
Study start: 11 Sep 2015 (actual)
Primary completion: 29 Apr 2020 (actual)
Study completion: 29 Apr 2020 (actual)
First posted: 19 Aug 2015 (estimated)
Results: Posted 18 May 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Part 1A: GSK3174998 Monotherapy- Dose escalation	Experimental	Drug: GSK3174998Participants will receive GSK3174998 intravenously (IV) (dose range 0.003 to 10.0 milligram per kilogram [mg/kg]) every 3 weeks (Q3W) for up to 2 years or 35 cycles, whichever comes first.
Part 2A: GSK3174998+ pembrolizumab - Dose escalation	Experimental	Drug: GSK3174998, Drug: PembrolizumabParticipants will receive GSK3174998 IV (dose range 0.003 to 10.0 mg/kg) Q3W for up to 2 years or 35 cycles, whichever comes first + Pembrolizumab 200 mg IV Q3W for up to 2 years or 35 cycles, whichever comes first.
Part 2B: GSK3174998+ pembrolizumab - Cohort expansion	Experimental	Drug: GSK3174998, Drug: PembrolizumabParticipants will receive GSK3174998 IV (at one dose level shown to be tolerable in dose escalation of part 2A) Q3W for up to 2 years or 35 cycles, whichever comes first + Pembrolizumab 200 mg IV Q3W for 2 years or 35 cycles, whichever comes first.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (19 listed)

Provide signed, written informed consent.
Male and female participants, age >=18 years (at the time consent is obtained).
Histological documentation of locally advanced, recurrent or metastatic solid malignancy that has progressed after standard therapy appropriate for the specific tumor type, or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate. Participants should not have received more than 5 prior lines of therapy for advanced disease including both standards of care and investigational therapies. Participants whose cancers harbor molecular alterations for which targeted therapy is standard of care should have received health authority approved appropriate targeted therapy for their tumor types before enrollment.
Participants with the following solid tumors are eligible for screening: Non-small cell lung cancer (NSCLC), Squamous cell carcinoma of the head and neck (SCCHN), Renal cell carcinoma (RCC), melanoma, bladder, Soft Tissue Sarcoma (STS), Triple-negative breast cancer (TNBC), and Colorectal carcinoma displaying high microsatellite instability (MSI CRC). In Part 2B (Cohort Expansion), specific subgroups of the above solid tumors will be studied. These subgroups may be defined by specific lines of treatment, types of prior treatment, histological subtypes, and may be enriched for selected biomarkers or participant characteristics. Populations to be studied in Amendment 3 include but are not limited to the following. Enrolment of additional populations will be communicated in writing: Participants with dedifferentiated liposarcoma who have not received prior treatment with a Programmed death ligand 1 (PD-L1) inhibitor; Participants with melanoma who have received a prior PD-L1 inhibitor, had a CR, PR or SD and subsequently progressed while on PD-L1 therapy. Participants who have received prior treatment with a PD-L1 inhibitor must have documented disease progression as defined by meeting all of the following criteria: Has received at least 2 doses of an approved PD-L1 inhibitor; has demonstrated disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The initial evidence of disease progression is to be confirmed by a second assessment no less than four weeks from the date of the first documented PD , in the absence of rapid clinical progression; Progressive disease has been documented within 18 weeks from the last dose of the PD-L1 inhibitor.
In Parts 1A and 2A, a biopsy of the tumor tissue obtained at anytime from the initial diagnosis to study entry. Although a fresh biopsy obtained during screening is preferred, archival tumor specimen is acceptable if it is not feasible to obtain a fresh biopsy.

Key exclusion criteria (23 listed)

Prior treatment with the following agents (from last dose of prior treatment to first dose of GSK3174998): Tumor necrosis factor receptor (TNFR) agonists, including OX40, CD27, CD137 (4-1BB), CD357 (GITR): at any time; Checkpoint inhibitors, including Programmed death receptor-1 (PD-1),
1, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors: within 4 weeks; other anticancer therapy, including chemotherapy, targeted therapy, and biological therapy: within 4 weeks or 5 half lives of the drug, whichever is shorter. Prior radiation therapy is permissible if at least one unirradiated measurable lesion is available for assessment via RECIST version 1.1. A wash out of at least two weeks before start of study drug for palliative radiation to the extremities for osseous bone metastases and 4 weeks for radiation to the chest, brain, or visceral organs is required; Investigational therapy: if the participant has participated in a clinical trial and has received an investigational product: within 30 days or 5 half-lives of the investigational product (whichever is shorter). At least 14 days must have passed between the last dose of prior investigational agent and the first dose of study drug.
Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.
Toxicity from previous treatment: Participants with >=Grade 3 toxicity related to prior immunotherapy leading to study treatment discontinuation are not eligible; participants whose toxicity related to prior treatment has not resolved to <=Grade 1 (except alopecia, hearing loss, grade <=2 neuropathy or endocrinopathy managed with replacement therapy) are not eligible.
Malignancy other than disease under study, except as noted below: any other malignancy from which the participant has been disease-free for more than 2 years and, in the opinion of the principal investigators and GSK Medical Monitor, will not affect the evaluation of the effects of this clinical trial treatment on currently targeted malignancy, can be included in this clinical trial.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK3174998Lyophilized powder 40 mg reconstituted to get a dose range of 0.003 to <=10 mg/kg to be given as IV infusion for 30 minutes (min), Q3W	Drug	Part 1A: GSK3174998 Monotherapy- Dose escalation, Part 2A: GSK3174998+ pembrolizumab - Dose escalation, Part 2B: GSK3174998+ pembrolizumab - Cohort expansion
PembrolizumabPembrolizumab as 100 mg/4 milliliter (mL) solution (dose: 200 mg) to be given as IV infusion for 30 min, Q3W	Drug	Part 2A: GSK3174998+ pembrolizumab - Dose escalation, Part 2B: GSK3174998+ pembrolizumab - Cohort expansion

Primary outcome

Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE)
Time frame: 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.
Part 2A: Number of Participants With Any SAE and Non-SAE
Time frame: 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.
Part 2B: Number of Participants With Any SAE and Non-SAE
Time frame: 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.
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: 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 version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of >=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT.
Part 2A: Number of Participants With DLTs
Time frame: 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 version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of >=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT.
Part 2B: Number of Participants With DLTs
Time frame: 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 version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of >=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT.
Part 1: Number of Participants With Any Adverse Event Leading to Withdrawal (AELD) From the Study
Time frame: 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.
Part 2A: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study
Time frame: 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.
Part 2B: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study
Time frame: 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.
Part 1: Number of Participants With Dose Reductions or Delay
Time frame: Up to maximum 39 weeks
Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented.
Part 2A: Number of Participants With Dose Reductions or Delay
Time frame: Up to maximum 105 weeks
Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented.
Part 2B: Number of Participants With Dose Reductions or Delay
Time frame: Up to maximum 33 weeks
Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented.
Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters
Time frame: Baseline (Day 1) and up to maximum 39 weeks
Blood samples were collected for the analysis of following hematology parameters: hemoglobin (Hb), leukocyte count (leuko.), lymphocyte count (Lymph.), neutrophil count (Neutro.) and platelet count (PC). The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters
Time frame: Baseline (Day 1) and up to maximum 105 weeks
Blood samples were collected for the analysis of following hematology parameters: Hb, leuko., Lymph., Neutro. and PC. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters
Time frame: Baseline (Day 1) and up to maximum 33 weeks
Blood samples were collected for the analysis of following hematology parameters: Hb, leuko., Lymph., Neutro. and PC. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters
Time frame: Baseline (Day 1) and up to maximum 39 weeks
Blood samples were collected for the analysis of following liver function laboratory parameters: alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters
Time frame: Baseline (Day 1) and up to maximum 105 weeks
Blood samples were collected for the analysis of following liver function laboratory parameters: ALT, ALP, AST and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters
Time frame: Baseline (Day 1) and up to maximum 33 weeks
Blood samples were collected for the analysis of following liver function laboratory parameters: ALT, ALP, AST and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time frame: Baseline (Day 1) and up to maximum 39 weeks
SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: <120 millimeter mercury (mmHg); Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: >=160 mmHg. For DBP: Grade 0: <80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: >=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP
Time frame: Baseline (Day 1) and up to maximum 105 weeks
SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: <120 mmHg; Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: >=160 mmHg. For DBP: Grade 0: <80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: >=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Part 2B: Number of Participants With Any Grade Change From Baseline in SBP and DBP
Time frame: Baseline (Day 1) and up to maximum 33 weeks
SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: <120 mmHg; Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: >=160 mmHg. For DBP: Grade 0: <80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: >=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR)
Time frame: Baseline (Day 1) and up to maximum 39 weeks
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: <60 beats per minute [bpm]', normal HR: 60 to 100 bpm and high HR: >100 bpm. If values were unchanged (example: increase to >100 bpm to increase to >100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Part 2A: Number of Participants With Worst Case Change From Baseline in HR
Time frame: Baseline (Day 1) and up to maximum 105 weeks
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: <60 bpm', normal HR: 60 to 100 bpm and high HR: >100 bpm. If values were unchanged (example: increase to >100 bpm to increase to >100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Part 2B: Number of Participants With Worst Case Change From Baseline in HR
Time frame: Baseline (Day 1) and up to maximum 33 weeks
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: <60 bpm', normal HR: 60 to 100 bpm and high HR: >100 bpm. If values were unchanged (example: increase to >100 bpm to increase to >100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature
Time frame: Baseline (Day 1) and up to maximum 39 weeks
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: <=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: >=38 degrees Celsius. If values were unchanged (example: increase to >=38 degrees Celsius to increase to >=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature
Time frame: Baseline (Day 1) and up to maximum 105 weeks
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: <=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: >=38 degrees Celsius. If values were unchanged (example: increase to >=38 degrees Celsius to increase to >=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Part 2B: Number of Participants With Worst Case Change From Baseline in Body Temperature
Time frame: Baseline (Day 1) and up to maximum 33 weeks
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: <=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: >=38 degrees Celsius. If values were unchanged (example: increase to >=38 degrees Celsius to increase to >=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Part 1: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant Electrocardiogram (ECG) Findings
Time frame: Up to maximum 39 weeks
A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented.
Part 2A: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings
Time frame: Up to maximum 105 weeks
A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented.
Part 2B: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings
Time frame: Up to maximum 33 weeks
A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented.

28 secondary outcomes

Part 1: Objective Response Rate (ORR)
Time frame: Up to maximum 39 weeks
Part 2A: Objective Response Rate (ORR)
Time frame: Up to maximum 105 weeks
Part 2B: Objective Response Rate (ORR)
Time frame: Up to maximum 33 weeks
Part 1: Disease Control Rate (DCR)
Time frame: Up to maximum 39 weeks
Part 2A: Disease Control Rate (DCR)
Time frame: Up to maximum 105 weeks
Part 2B: Disease Control Rate (DCR)
Time frame: Up to maximum 33 weeks
Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion
Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion
Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion
Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Part 2A: AUC(0-tau) of GSK3174998
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Part 2B: AUC(0-tau) of GSK3174998
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Part 2A: Cmax and Cmin of GSK3174998
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Part 2B: Cmax and Cmin of GSK3174998
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points
Time frame: Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22, 64, 106
Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points
Time frame: Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22, 64, 106
Part 2A: AUC(0-tau) of Pembrolizumab
Time frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days)
Part 2B: AUC(0-tau) of Pembrolizumab
Time frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days)
Part 2A: Cmax of Pembrolizumab
Time frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days)
Part 2B: Cmax of Pembrolizumab
Time frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days)
Part 2A: Cmin of Pembrolizumab
Time frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days)
Part 2B: Cmin of Pembrolizumab
Time frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days)
Part 1: Number of Participants With Positive Antidrug Antibodies (ADAs) Against GSK3174998
Time frame: Up to maximum 39 weeks
Part 2A: Number of Participants With Positive ADAs Against GSK3174998
Time frame: Up to maximum 105 weeks
Part 2B: Number of Participants With Positive ADAs Against GSK3174998
Time frame: Up to maximum 33 weeks
Part 2A: Number of Participants With Positive ADAs Against Pembrolizumab
Time frame: Up to maximum 105 weeks
Part 2B: Number of Participants With Positive ADAs Against Pembrolizumab
Time frame: Up to maximum 33 weeks

Results and safety

Results posted to the registry on 18 May 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1: GSK3174998 0.003 mg/kg	1	1
Part 1: GSK3174998 0.01 mg/kg	1	0
Part 1: GSK3174998 0.03 mg/kg	8	6
Part 1: GSK3174998 0.1 mg/kg	10	9
Part 1: GSK3174998 0.3 mg/kg	10	6
Part 1: GSK3174998 1.0 mg/kg	4	2
Part 1: GSK3174998 3.0 mg/kg	7	5
Part 1: GSK3174998 10.0 mg/kg	4	2
Part 2A: GSK3174998 0.003 mg/kg + Pembrolizumab 200 mg	0	0
Part 2A: GSK3174998 0.01 mg/kg + Pembrolizumab 200 mg	0	0
Part 2A: GSK3174998 0.03 mg/kg + Pembrolizumab 200 mg	0	0
Part 2A: GSK3174998 0.1 mg/kg + Pembrolizumab 200 mg	0	0
Part 2A: GSK3174998 0.3 mg/kg + Pembrolizumab 200 mg	0	0
Part 2A: GSK3174998 1.0 mg/kg + Pembrolizumab 200 mg	0	0
Part 2A: GSK3174998 3.0 mg/kg + Pembrolizumab 200 mg	0	0
Part 2A: GSK3174998 10.0 mg/kg + Pembrolizumab 200 mg	0	0
Part 2B: Melanoma Cohort	0	0
Part 2B: Soft Tissue Sarcoma Cohort	0	0
Part 2B: NSCLC Cohort	0	0

Primary outcome: Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE)

Time frame: Up to maximum 39 weeks. Count of participants. Unit: Participants

Measure	Part 1: GSK3174998 0.003 mg/kg n = 1	Part 1: GSK3174998 0.01 mg/kg n = 1	Part 1: GSK3174998 0.03 mg/kg n = 8	Part 1: GSK3174998 0.1 mg/kg n = 10	Part 1: GSK3174998 0.3 mg/kg n = 10	Part 1: GSK3174998 1.0 mg/kg n = 4	Part 1: GSK3174998 3.0 mg/kg n = 7	Part 1: GSK3174998 10.0 mg/kg n = 4
Any SAE	1	0	3	7	2	1	2	1
Any non-SAE	1	1	8	10	10	4	7	4

Population analysed: All Treated Population consisted of all participants who received at least one dose of GSK3174998.

Primary outcome: Part 2A: Number of Participants With Any SAE and Non-SAE

Time frame: Up to maximum 105 weeks. Count of participants. Unit: Participants

Measure	Part 2A: GSK3174998 0.003 mg/kg + Pembrolizumab 200 mg n = 5	Part 2A: GSK3174998 0.01 mg/kg + Pembrolizumab 200 mg n = 5	Part 2A: GSK3174998 0.03 mg/kg + Pembrolizumab 200 mg n = 10	Part 2A: GSK3174998 0.1 mg/kg + Pembrolizumab 200 mg n = 12	Part 2A: GSK3174998 0.3 mg/kg + Pembrolizumab 200 mg n = 14	Part 2A: GSK3174998 1.0 mg/kg + Pembrolizumab 200 mg n = 12	Part 2A: GSK3174998 3.0 mg/kg + Pembrolizumab 200 mg n = 12	Part 2A: GSK3174998 10.0 mg/kg + Pembrolizumab 200 mg n = 4
Any SAE	1	1	6	4	4	4	2	2
Any non-SAE	5	5	10	12	13	12	12	4

Population analysed: All Treated Population

Primary outcome: Part 2B: Number of Participants With Any SAE and Non-SAE

Time frame: Up to maximum 33 weeks. Count of participants. Unit: Participants

Measure	Part 2B: Melanoma Cohort n = 9	Part 2B: Soft Tissue Sarcoma Cohort n = 8	Part 2B: NSCLC Cohort n = 5
Any SAE	1	2	1
Any non-SAE	9	8	4

Population analysed: All Treated Population

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

Time frame: 28 days. Count of participants. Unit: Participants

Measure	Part 1: GSK3174998 0.003 mg/kg n = 1	Part 1: GSK3174998 0.01 mg/kg n = 1	Part 1: GSK3174998 0.03 mg/kg n = 8	Part 1: GSK3174998 0.1 mg/kg n = 10	Part 1: GSK3174998 0.3 mg/kg n = 10	Part 1: GSK3174998 1.0 mg/kg n = 4	Part 1: GSK3174998 3.0 mg/kg n = 7	Part 1: GSK3174998 10.0 mg/kg n = 4
Value	0	0	0	0	0	0	0	0

Population analysed: All Treated Population

28 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 39 weeks in Part 1; Up to 105 weeks in Part 2A; Up to 33 weeks in Part 2B. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1: GSK3174998 0.003 mg/kg	1 of 1 (100%)	1 of 1 (100%)	1 of 1
Part 1: GSK3174998 0.01 mg/kg	0 of 1 (0%)	1 of 1 (100%)	0 of 1
Part 1: GSK3174998 0.03 mg/kg	3 of 8 (37.5%)	8 of 8 (100%)	6 of 8
Part 1: GSK3174998 0.1 mg/kg	7 of 10 (70%)	10 of 10 (100%)	9 of 10
Part 1: GSK3174998 0.3 mg/kg	2 of 10 (20%)	10 of 10 (100%)	6 of 10
Part 1: GSK3174998 1.0 mg/kg	1 of 4 (25%)	4 of 4 (100%)	2 of 4
Part 1: GSK3174998 3.0 mg/kg	2 of 7 (28.6%)	7 of 7 (100%)	5 of 7
Part 1: GSK3174998 10.0 mg/kg	1 of 4 (25%)	4 of 4 (100%)	2 of 4
Part 2A: GSK3174998 0.003 mg/kg + Pembrolizumab 200 mg	1 of 5 (20%)	5 of 5 (100%)	4 of 5
Part 2A: GSK3174998 0.01 mg/kg + Pembrolizumab 200 mg	1 of 5 (20%)	5 of 5 (100%)	4 of 5
Part 2A: GSK3174998 0.03 mg/kg + Pembrolizumab 200 mg	6 of 10 (60%)	10 of 10 (100%)	7 of 10
Part 2A: GSK3174998 0.1 mg/kg + Pembrolizumab 200 mg	4 of 12 (33.3%)	12 of 12 (100%)	9 of 12
Part 2A: GSK3174998 0.3 mg/kg + Pembrolizumab 200 mg	4 of 14 (28.6%)	13 of 14 (92.9%)	9 of 14
Part 2A: GSK3174998 1.0 mg/kg + Pembrolizumab 200 mg	4 of 12 (33.3%)	12 of 12 (100%)	6 of 12
Part 2A: GSK3174998 3.0 mg/kg + Pembrolizumab 200 mg	2 of 12 (16.7%)	12 of 12 (100%)	5 of 12
Part 2A: GSK3174998 10.0 mg/kg + Pembrolizumab 200 mg	2 of 4 (50%)	4 of 4 (100%)	4 of 4
Part 2B: Melanoma Cohort	1 of 9 (11.1%)	9 of 9 (100%)	6 of 9

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36927527Postel-Vinay S, Lam VK, Ros W, Bauer TM, Hansen AR, Cho DC, Stephen Hodi F, Schellens JHM, Litton JK, Aspeslagh S, Autio KA, Opdam FL, McKean M, Somaiah N, Champiat S, Altan M, Spreafico A, Rahma O, Paul EM, Ahlers CM, Zhou H, Struemper H, Gorman SA, Watmuff M, Yablonski KM, Yanamandra N, Chisamore MJ, Schmidt EV, Hoos A, Marabelle A, Weber JS, Heymach JV. First-in-human phase I study of the OX40 agonist GSK3174998 with or without pembrolizumab in patients with selected advanced solid tumors (ENGAGE-1). J Immunother Cancer. 2023 Mar;11(3):e005301. doi: 10.1136/jitc-2022-005301.
Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

8 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK3174998 and Pembrolizumab in people with Neoplasms, run by GlaxoSmithKline at 8 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Canada, France, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) (time frame: Up to maximum 39 weeks). The study lists 30 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02528357, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2021.