Study of MK-1248 With and Without Pembrolizumab (MK-3475)... | NCT02553499

NCT02553499

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
MK-1248-001	Other Identifier	Merck

Status Module

Sponsor/Collaborators Module

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
MK-1248	Experimental	Participants received escalating doses of MK-1248 at assigned dose (dose range: 0.12 mg to 170 mg MK-1248) via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to ~3 months).	Biological: MK-1248
MK-1248 + Pembrolizumab	Experimental	Participants received escalating doses of MK-1248 at assigned dose (dose range: 0.12 mg to 60 mg MK-1248) via IV infusion on Day 1 of each 21-day cycle for a maximum of 4 cycles (up to ~3 months) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to ~24 months).	Biological: MK-1248 Biological: pembrolizumab

Name	Type	Description	Arm Group Labels	Other Names
MK-1248	Biological	IV infusion	MK-1248 MK-1248 + Pembrolizumab

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants Experiencing a Dose-Limiting Toxicity (DLT)	The occurrence of any of the following toxicities during Cycle 1 (21 days), if possibly, probably or definitely related to study treatment, was considered a DLT: 1. Grade 4 non-hematological toxicity 2. Grade 4 hematological toxicity lasting >7 days, except thrombocytopenia a. Grade 4 thrombocytopenia of any duration b. Grade 3 thrombocytopenia is a DLT if associated with bleeding 3. Any Grade 3 non-hematological toxicity, with the exceptions 4. Any Grade 3 or Grade 4 non-hematological laboratory abnormality, if medical intervention was required, or abnormality led to hospitalization, or abnormality persisted for >1 week 5. Febrile neutropenia Grade 3 or Grade 4 6. Any drug-related AE which caused participant to discontinue study treatment during Cycle 1 7. Grade 5 toxicity 8. Any treatment-related toxicity which caused a >2-week delay in initiation of Cycle 2.	Cycle 1 (Up to 21 days)

Secondary Outcomes

Measure	Description	Time Frame
Maximum Concentration (Cmax) of MK-1248 in Serum	Cmax is the maximum (peak) concentration of MK-1248 observed in blood serum. Blood samples were obtained at designated timepoints for the analysis of MK-1248 Cmax. Timepoints: Cycles 1-4 Day 1: Predose, post MK-1248 infusion end (~0.5 hours), 2 hours post MK-1248 infusion start (~2 hours); Cycles 1-4 Days 2, 3, 5, 8 & 15. Each cycle was 21 days. (Up to ~3 months)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologically- or cytologically-confirmed metastatic solid tumor for which there is no available therapy that may convey clinical benefit
Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria
Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
Adequate organ function
Female participants of childbearing potential should be willing to use adequate contraception for the course of the study through 120 days after the last dose of study medication
Male participants should agree to use adequate contraception starting with the first dose of study therapy through 180 days after the last dose of study medication
Can submit a baseline tumor sample

Exclusion Criteria:

Has had chemotherapy, radiation, or biological cancer therapy within 4 weeks prior to the first dose of study medication, or not recovered from adverse events due to cancer therapeutics administered more than 4 weeks earlier
Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study medication
Previous treatment with another agent targeting the glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) receptor
Previous treatment with an immunomodulatory therapy and was discontinued from that therapy due to an immune-related adverse event
Expected to require any other form of antineoplastic therapy while on study
On chronic systemic steroid therapy in excess of replacement doses, or on any other form of immunosuppressive medication
History of a previous, additional malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years with the exception of successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Severe hypersensitivity reaction to treatment with another monoclonal antibody
Active autoimmune disease or a documented history of autoimmune disease with the exception of vitiligo or resolved childhood asthma/atopy, or endocrine deficiency following treatment with an immunomodulatory agent
Active infection requiring therapy
Active or a history of non-infectious pneumonitis
Prior stem cell or bone marrow transplant
Known history of human immunodeficiency virus (HIV), active chronic or acute hepatitis B or C
Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
Regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol), at the time of signing informed consent
Symptomatic ascites or pleural effusion
Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study through 180 days after the last dose of study medication
Major surgery within 16 weeks prior to screening
Live vaccine within 30 days prior to first dose of study medication

Contacts/Locations Module

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
32809217	Derived	Geva R, Voskoboynik M, Dobrenkov K, Mayawala K, Gwo J, Wnek R, Chartash E, Long GV. First-in-human phase 1 study of MK-1248, an anti-glucocorticoid-induced tumor necrosis factor receptor agonist monoclonal antibody, as monotherapy or with pembrolizumab in patients with advanced solid tumors. Cancer. 2020 Nov 15;126(22):4926-4935. doi: 10.1002/cncr.33133. Epub 2020 Aug 18.

IPD Sharing Statement Module

No data available

No data is available for this block.

Arm/Group Information

ID	Title	Description
FG000	MK-1248 0.12 mg	Participants received MK-1248 0.12 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).
FG001	MK-1248 0.6 mg	Participants received MK-1248 0.6 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).
FG002	MK-1248 3 mg	Participants received MK-1248 3 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).
FG003	MK-1248 10 mg	Participants received MK-1248 10 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).
FG004	MK-1248 30 mg	Participants received MK-1248 30 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).
FG005	MK-1248 60 mg	Participants received MK-1248 60 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).
FG006	MK-1248 120 mg	Participants received MK-1248 120 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).
FG007	MK-1248 170 mg	Participants received MK-1248 170 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).
FG008	MK-1248 0.12 mg + Pembrolizumab	Participants received MK-1248 0.12 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 24 months).
FG009	MK-1248 0.6 mg + Pembrolizumab	Participants received MK-1248 0.6 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 24 months).
FG010	MK-1248 3 mg + Pembrolizumab	Participants received MK-1248 3 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 24 months).
FG011	MK-1248 10 mg + Pembrolizumab	Participants received MK-1248 10 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 24 months).
FG012	MK-1248 30 mg + Pembrolizumab	Participants received MK-1248 30 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 24 months).
FG013	MK-1248 60 mg + Pembrolizumab	Participants received MK-1248 60 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 24 months).

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0002 subjects FG0012 subjects FG0022 subjects FG0032 subjects FG0043 subjects FG0053 subjects FG0063 subjects FG0073 subjects FG0083 subjects FG0093 subjects FG0103 subjects FG0113 subjects FG0123 subjects FG0132 subjects
COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
NOT COMPLETED		FG0002 subjects FG0012 subjects FG0022 subjects FG0032 subjects FG004

Type	Comment	Reasons
Adverse Event		FG0000 subjects FG0010 subjects FG0020 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	MK-1248 0.12 mg	Participants received MK-1248 0.12 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).
BG001	MK-1248 0.6 mg

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

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

Number of Participants Experiencing a Dose-Limiting Toxicity (DLT)

The occurrence of any of the following toxicities during Cycle 1 (21 days), if possibly, probably or definitely related to study treatment, was considered a DLT: 1. Grade 4 non-hematological toxicity 2. Grade 4 hematological toxicity lasting >7 days, except thrombocytopenia a. Grade 4 thrombocytopenia of any duration b. Grade 3 thrombocytopenia is a DLT if associated with bleeding 3. Any Grade 3 non-hematological toxicity, with the exceptions 4. Any Grade 3 or Grade 4 non-hematological laboratory abnormality, if medical intervention was required, or abnormality led to hospitalization, or abnormality persisted for >1 week 5. Febrile neutropenia Grade 3 or Grade 4 6. Any drug-related AE which caused participant to discontinue study treatment during Cycle 1 7. Grade 5 toxicity 8. Any treatment-related toxicity which caused a >2-week delay in initiation of Cycle 2.

The DLT analysis population consisted of all participants who received MK-1248 and were observed for safety for 21 days after the first dose of MK-1248 or experienced a DLT prior to 21 days after the first dose of MK-1248.

Posted

Count of Participants

Participants

Cycle 1 (Up to 21 days)

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	MK-1248 0.12 mg	Participants received MK-1248 0.12 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Senior Vice President, Global Clinical Development	Merck Sharp & Dohme Corp.	1-800-672-6372		ClinicalTrialsDisclosure@merck.com

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Nov 6, 2017	Aug 30, 2019	Prot_SAP_000.pdf

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

ID	Term
C582435	pembrolizumab

Masking Info

Participants received MK-1248 0.6 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).

EG0000 events0 affected2 at risk

EG0011 events1 affected2 at risk

EG0020 events0 affected2 at risk

EG0030 events0 affected2 at risk

EG0040 events0 affected3 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected3 at risk

EG0080 events0 affected3 at risk

EG0090 events0 affected3 at risk

EG0100 events0 affected3 at risk

EG0110 events0 affected3 at risk

EG0120 events0 affected3 at risk

EG0130 events0 affected2 at risk

EG0000 events0 affected2 at risk

EG0010 events0 affected2 at risk

EG0020 events0 affected2 at risk

EG0030 events0 affected2 at risk

EG0040 events0 affected3 at risk

EG0051 events1 affected3 at risk

EG0060 events0 affected3 at risk

EG0072 events2 affected3 at risk

EG0082 events2 affected3 at risk

EG0091 events1 affected3 at risk

EG0101 events1 affected3 at risk

EG0112 events2 affected3 at risk

EG0120 events0 affected3 at risk

EG0132 events1 affected2 at risk

OG01296.7± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG0056240000± 481.2

OG00641500000± 40.0

OG0076980000± 24178.9

OG01210400000± 43.4

OG01316900000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

NA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG00410200000± 65.9

OG00521500000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG00652600000± 46.9

OG00767400000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG01212300000± 30.3

OG01316100000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

NA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG00512600000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG00670700000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG00766300000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG01212200000± 45.2

OG01312800000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

NA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG0069530000± 130.5

OG007828000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG0122180000± 130.0

OG013295000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

NA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG00625600000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG007119000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG00848.8± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG0121670000± 290.5

OG01315700± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG005105000000± 304.5

OG006604000000± 111.5

OG007341000000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG01264900000± 285.6

OG01377300000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

NA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG006737000000± 172.7

OG007218000000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG008393000± 1325.8

OG012139000000± 125.9

OG01331500000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

NA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG007250000000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG0113040000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG012112000000± 259.6

OG01322100000± NANA=Geometric Coefficient of Variation could not be calculated with only 1 participant

OG000	MK-1248 0.12 mg	Participants received MK-1248 0.12 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).
OG001	MK-1248 0.6 mg	Participants received MK-1248 0.6 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).
OG002	MK-1248 3 mg	Participants received MK-1248 3 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).
OG003	MK-1248 10 mg	Participants received MK-1248 10 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).
OG004	MK-1248 30 mg	Participants received MK-1248 30 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).
OG005	MK-1248 60 mg	Participants received MK-1248 60 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).
OG006	MK-1248 120 mg	Participants received MK-1248 120 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).
OG007	MK-1248 170 mg	Participants received MK-1248 170 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months).
OG008	MK-1248 0.12 mg + Pembrolizumab	Participants received MK-1248 0.12 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 24 months).
OG009	MK-1248 0.6 mg + Pembrolizumab	Participants received MK-1248 0.6 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 24 months).
OG010	MK-1248 3 mg + Pembrolizumab	Participants received MK-1248 3 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 24 months).
OG011	MK-1248 10 mg + Pembrolizumab	Participants received MK-1248 10 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 24 months).
OG012	MK-1248 30 mg + Pembrolizumab	Participants received MK-1248 30 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 24 months).
OG013	MK-1248 60 mg + Pembrolizumab	Participants received MK-1248 60 mg via IV infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to approximately 3 months) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 24 months).