GSK3174998 Alone and With Pembrolizumab in Participants W... | NCT02528357

NCT02528357

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2015-000152-14	EudraCT Number

Status Module

Sponsor/Collaborators Module

Name	Class
Merck Sharp & Dohme LLC	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.	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.	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.	Drug: GSK3174998 Drug: Pembrolizumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
GSK3174998	Drug	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	Part 1A: GSK3174998 Monotherapy- Dose escalation

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	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.	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.	Up to maximum 33 weeks
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

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.

Exclusion Criteria:

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.
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.](streamdown:incomplete-link)

Contacts/Locations Module

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Boston	Massachusetts	02215	United States
GSK Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
36927527	Derived	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.

IPD Sharing Statement Module

A total of 141 participants were enrolled in the study: 45 participants in Part 1 and 96 participants in Part 2 (74 in Part 2A+ 22 in Part 2B).

Arm/Group Information

ID	Title	Description
FG000	Part 1: GSK3174998 0.003 mg/kg	Participants received intravenous (IV) dose of GSK3174998 0.003 milligram per kilogram (mg/kg) every 3 weeks (wks) in Part 1.
FG001	Part 1: GSK3174998 0.01 mg/kg	Participants received IV dose of GSK3174998 0.01 mg/kg every 3 weeks (Q3W) in Part 1.
FG002	Part 1: GSK3174998 0.03 mg/kg	Participants received IV dose of GSK3174998 0.03 mg/kg Q3W in Part 1.
FG003	Part 1: GSK3174998 0.1 mg/kg	Participants received IV dose of GSK3174998 0.1 mg/kg Q3W in Part 1.
FG004	Part 1: GSK3174998 0.3 mg/kg	Participants received IV dose of GSK3174998 0.3 mg/kg Q3W in Part 1.
FG005	Part 1: GSK3174998 1.0 mg/kg	Participants received IV dose of GSK3174998 1.0 mg/kg Q3W in Part 1.
FG006	Part 1: GSK3174998 3.0 mg/kg	Participants received IV dose of GSK3174998 3.0 mg/kg Q3W in Part 1.
FG007	Part 1: GSK3174998 10.0 mg/kg	Participants received IV dose of GSK3174998 10.0 mg/kg Q3W in Part 1.
FG008	Part 2A: GSK3174998 0.003 mg/kg + Pembrolizumab 200 mg	Participants received IV dose of GSK3174998 0.003 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A.
FG009	Part 2A: GSK3174998 0.01 mg/kg + Pembrolizumab 200 mg	Participants received IV dose of GSK3174998 0.01 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A.
FG010	Part 2A: GSK3174998 0.03 mg/kg + Pembrolizumab 200 mg	Participants received IV dose of GSK3174998 0.03 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A.
FG011	Part 2A: GSK3174998 0.1 mg/kg + Pembrolizumab 200 mg	Participants received IV dose of GSK3174998 0.1 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A.
FG012	Part 2A: GSK3174998 0.3 mg/kg + Pembrolizumab 200 mg	Participants received IV dose of GSK3174998 0.3 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A.
FG013	Part 2A: GSK3174998 1.0 mg/kg + Pembrolizumab 200 mg	Participants received IV dose of GSK3174998 1.0 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A.
FG014	Part 2A: GSK3174998 3.0 mg/kg + Pembrolizumab 200 mg	Participants received IV dose of GSK3174998 3.0 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A.
FG015	Part 2A: GSK3174998 10.0 mg/kg + Pembrolizumab 200 mg	Participants received IV dose of GSK3174998 10.0 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A.
FG016	Part 2B: Melanoma Cohort	Participants with melanoma were included in this cohort and received IV dose of GSK3174998 0.3 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2B.
FG017	Part 2B: Soft Tissue Sarcoma Cohort	Participants with soft tissue sarcoma were included in this cohort and received IV dose of GSK3174998 0.3 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2B.
FG018	Part 2B: NSCLC Cohort	Participants with non-small cell lung cancer (NSCLC) were included in this cohort and received IV dose of GSK3174998 0.3 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2B.

Periods

Title

Milestones

Reasons Not Completed

Part1:Monotherapy(Up to Maximum 39weeks)

Type	Comment	Milestone Data
STARTED		FG0001 subjects FG0011 subjects FG0028 subjects FG00310 subjects FG004
COMPLETED		FG0001 subjects FG0010 subjects FG0026 subjects FG0039 subjects FG004
NOT COMPLETED		FG0000 subjects FG0011 subjects FG0022 subjects FG0031 subjects FG004

Type	Comment	Reasons
Lost to Follow-up		FG0000 subjects FG0011 subjects FG0020 subjects FG003

Part2A:Comb. Th. (Up to Maximum 105wks)

Type	Comment	Milestone Data
STARTED		FG0000 subjects FG0010 subjects FG0020 subjects FG003

Part2B:Expan. Coh.(Up to Maximum 33 Wks)

Type	Comment	Milestone Data
STARTED		FG0000 subjects FG0010 subjects FG0020 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Part 1: GSK3174998 0.003 mg/kg	Participants received intravenous (IV) dose of GSK3174998 0.003 milligram per kilogram (mg/kg) every 3 weeks (wks) in Part 1.
BG001	Part 1: GSK3174998 0.01 mg/kg

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Customized			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

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

Posted

Count of Participants

Participants

Up to maximum 39 weeks

ID	Title	Description
OG000	Part 1: GSK3174998 0.003 mg/kg	Participants received intravenous (IV) dose of GSK3174998 0.003 milligram per kilogram (mg/kg) every 3 weeks (wks) in Part 1.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part 1: GSK3174998 0.003 mg/kg	Participants received intravenous (IV) dose of GSK3174998 0.003 milligram per kilogram (mg/kg) every 3 weeks (wks) in Part 1.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
GSK Response Center	GlaxoSmithKline	866-435-7343		GSKClinicalSupportHD@gsk.com

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 4, 2020	Apr 1, 2021	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	May 19, 2020	Apr 6, 2021	SAP_001.pdf

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D009369	Neoplasms
D002289	Carcinoma, Non-Small-Cell Lung

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms

Intervention Browse Module

ID	Term
C582435	pembrolizumab

Masking Info

Part 2A: GSK3174998+ pembrolizumab - Dose escalation

Part 2B: GSK3174998+ pembrolizumab - Cohort expansion

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.

Participants received IV dose of GSK3174998 0.01 mg/kg every 3 weeks (Q3W) in Part 1.

EG0000 events0 affected1 at risk

EG0010 events0 affected1 at risk

EG0020 events0 affected8 at risk

EG0030 events0 affected10 at risk

EG0041 events1 affected10 at risk

EG0050 events0 affected4 at risk

EG0060 events0 affected7 at risk

EG0070 events0 affected4 at risk

EG0080 events0 affected5 at risk

EG0090 events0 affected5 at risk

EG0100 events0 affected10 at risk

EG0110 events0 affected12 at risk

EG0120 events0 affected14 at risk

EG0130 events0 affected12 at risk

EG0140 events0 affected12 at risk

EG0150 events0 affected4 at risk

EG0160 events0 affected9 at risk

EG0170 events0 affected8 at risk

EG0180 events0 affected5 at risk

EG0001 events1 affected1 at risk

EG0010 events0 affected1 at risk

EG0021 events1 affected8 at risk

EG0032 events2 affected10 at risk

EG0042 events2 affected10 at risk

EG0051 events1 affected4 at risk

EG0060 events0 affected7 at risk

EG0070 events0 affected4 at risk

EG0081 events1 affected5 at risk

EG0090 events0 affected5 at risk

EG0100 events0 affected10 at risk

EG0112 events2 affected12 at risk

EG0122 events1 affected14 at risk

EG0134 events3 affected12 at risk

EG0141 events1 affected12 at risk

EG0150 events0 affected4 at risk

EG0160 events0 affected9 at risk

EG0172 events2 affected8 at risk

EG0180 events0 affected5 at risk

BG019NATotal not calculated because data are not available (NA) in one or more arms.

Title	Measurements
	OG0009 OG0018 OG0024

Title	Measurements
	OG0000 OG0010 OG0020

Title	Measurements
	OG0000 OG0010 OG0020

Title	Measurements
	OG0003 OG0014 OG0020

Title	Measurements
	OG0005 OG0015 OG0023

OG00211.940± 7.3057

OG00523.224± 5.2813

OG00677.500± 17.8619

OG007277.615± 30.9564

OG00521.533± 5.5070

OG00670.603± 15.1388

OG007243.701± 42.5698

OG00517.645± 3.8210

OG00659.143± 12.1864

OG007191.862± 35.7293

OG00632.974± 8.4840

OG007108.278± 44.5563

OG00621.705± 6.4334

OG00780.909± 27.3394

OG00615.185± 4.1187

OG00758.537± 17.2736

OG00525.859± 9.2995

OG00681.115± 32.5472

OG007321.132± 40.4375

OG00522.905± 9.6502

OG00682.690± 18.1793

OG007306.585± 31.7702

OG00517.869± 9.3910

OG00672.801± 17.5925

OG007260.830± 44.1526

OG00642.013± 13.3448

OG007153.655± 37.5871

OG00631.093± 10.5909

OG007111.545± 22.8298

OG00621.658± 8.9413

OG00782.723± 26.1829

OG00530.602± 0.6521

OG00695.775± 22.9300

OG007302.882± 3.7341

OG00623.922± 9.6447

OG00776.602± 27.6046

OG00698.410± 19.0269

OG007312.277± 61.0388

OG00622.635± 3.1816

OG00783.090± 31.8311

OG00682.402± 18.5192

OG007294.788± 15.9947

OG00619.047± NAStandard deviation could not be calculated due to single participant

OG00794.359± 11.4639

Standard deviation could not be calculated due to single participant

OG007307.222± 3.5048

OG00525.623± 6.4576

OG00670.550± 16.4984

OG007193.082± 30.6483

OG00523.367± 4.5233

OG00666.831± 17.5167

OG007178.023± 20.6597

OG00519.398± 5.6732

OG00655.782± 13.0007

OG007140.747± 9.5100

OG00512.151± 8.5380

OG00630.442± 8.6063

OG00771.830± 14.1731

OG00622.050± 6.8631

OG00750.342± 12.5709

OG00616.354± 5.5789

OG00731.882± 12.4466

OG00530.238± 4.8782

OG00685.882± 16.2709

OG007222.118± 45.7084

OG00527.273± 6.0059

OG00682.796± 16.8542

OG007205.085± 26.1667

OG00521.631± 8.6914

OG00669.978± 13.9446

OG007164.798± 36.7704

OG00511.961± 5.5511

OG00645.527± 14.7008

OG00767.369± NAStandard deviation could not be calculated due to single participant

OG00633.671± 10.9055

OG007106.605± NAStandard deviation could not be calculated due to single participant

OG00624.578± 8.5351

OG00774.088± NAStandard deviation could not be calculated due to single participant

OG00528.433± 5.1446

OG00694.463± 20.9570

OG007377.078± NAStandard deviation could not be calculated due to single participant

OG00632.716± 11.1159

OG00533.382± 5.0217

OG00699.623± 25.2220

OG00635.166± 13.8402

OG006100.514± 26.7950

OG00636.990± 16.0967

OG006108.103± 29.3324

OG0072801.8± NAGeometric coefficient of variation could not be calculated due to single participant

OG007377.1± NAGeometric coefficient of variation could not be calculated due to single participant

OG00774.09± NAGeometric coefficient of variation could not be calculated due to single participant

OG00459.175± 24.1666

OG00575.857± 21.3825

OG00666.100± 15.2560

OG00765.100± 15.6721

OG00453.810± 32.8301

OG00554.442± 17.3552

OG00651.842± 16.3551

OG00748.900± 15.1969

OG00430.757± 13.6721

OG00535.600± 16.0615

OG00632.792± 9.0537

OG00734.025± 11.7196

OG00421.369± 10.9198

OG00526.525± 16.4784