Dose Evaluation of MK-1966 in Combination With SD-101 in... | NCT02731742

NCT02731742

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-1966-001	Other Identifier	Merck Protocol Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Dose A MK-1966 + Dose A SD-101	Experimental	Participants received a combination of MK-1966 (Days 1 and 21) and SD-101 (Days 1, 8, 15 and Day 22) in Part A of the study (approximately 21 days). Participants were to continue in one of two expansion cohorts (Part B or C) and receive up to 8 cycles of treatment (approximately 24 weeks). Each cycle was 21 days.	Biological: MK-1966 Drug: SD-101
Dose A MK-1966 + Dose B SD-101	Experimental	Participants received a combination of MK-1966 (Days 1 and 21) and SD-101 (Days 1, 8, 15 and Day 22) in Part A of the study (approximately 21 days). Participants were to continue in one of two expansion cohorts (Part B or C) and receive up to 8 cycles of treatment (approximately 24 weeks). Each cycle was 21 days.	Biological: MK-1966 Drug: SD-101
Dose B MK-1966 + Dose B SD-101	Experimental	Participants received a combination of MK-1966 (Days 1 and 21) and SD-101 (Days 1, 8, 15 and Day 22) in Part A of the study (approximately 21 days). Participants were to continue in one of two expansion cohorts (Part B or C) and receive up to 8 cycles of treatment (approximately 24 weeks). Each cycle was 21 days.	Biological: MK-1966 Drug: SD-101
Dose C MK-1966 + Dose B SD-101	Experimental	Participants received a combination of MK-1966 (Days 1 and 21) and SD-101 (Days 1, 8, 15 and Day 22) in Part A of the study (approximately 21 days). Participants were to continue in one of two expansion cohorts (Part B or C) and receive up to 8 cycles of treatment (approximately 24 weeks). Each cycle was 21 days.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
MK-1966	Biological	MK-1966 administered as an intravenous (IV) infusion	Dose A MK-1966 + Dose A SD-101 Dose A MK-1966 + Dose B SD-101 Dose B MK-1966 + Dose B SD-101

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With a Dose Limiting Toxicity (DLT)	The occurrence of any of the following toxicities during Cycle 1 (Days 1-21), if assessed by the Investigator to be possibly, probably or definitely related to MK-1966 or SD-101, was considered a DLT: Grade (Gr) 4 non-hematologic toxicity; Gr 4 hematologic toxicity lasting >7 days, except thrombocytopenia: Gr 4 thrombocytopenia of any duration; Gr 3 thrombocytopenia if associated with bleeding; Gr 3 non-hematologic toxicity lasting >3 days despite optimal supportive care; Any Gr 3 or Gr 4 non-hematologic laboratory abnormality, if: medical intervention is required OR abnormality leads to hospitalization OR abnormality persists for >1 week; Febrile neutropenia Gr 3 or Gr 4; Any drug-related AE which caused participant to discontinue study drug during Cycle 1 Gr 5 toxicity; or Delay in initiation of Cycle 2 for >2 weeks due to study drug-related toxicity. The percentage of participants who experienced a DLT during Cycle 1 is presented.	From time of first dose of study drug to the end of Cycle 1. Each cycle was 21 days. (Up to 21 days)
Number of Participants With Adverse Events (AEs)	An AE was defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study drug or protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study drug, was also an AE. The number of participants who experienced as AE is presented.	From first dose of study drug through 90 days after last dose of study drug (Up to approximately 22 weeks)
Number of Participants Discontinuing Study Drug Due to AEs	The number of participants who discontinued study drug due to an AE is presented.	From first dose of study drug up to last dose of study drug (Up to approximately 9 weeks)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has a histologically- or cytologically-confirmed advanced malignancy that has progressed after standard-of-care therapy/treatments and there is no available therapy likely to convey clinical benefit
Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Has a life expectancy ≥ 6 months
Female participants must not be pregnant (negative urine or serum human chorionic gonadotropin test at screening and again within 72 hours prior to receiving the first dose of study therapy)
Female and male participants of reproductive potential must agree to use adequate contraception during the course of the study through 120 days after study the last dose of study therapy
Has ability to submit archived or fresh tumor sample during the screening period

Exclusion Criteria:

Has had chemotherapy, radiation, or biological cancer therapy within 4 weeks prior to the first dose of study therapy, or who has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or better from the adverse events due to cancer therapeutics administered more than 4 weeks earlier
Has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days of study start
Is expected to require any other form of antineoplastic therapy while on study
Is on chronic systemic steroid therapy in excess of replacement doses, or on any other form of immunosuppressive medication
Has a history of a malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has had a severe hypersensitivity reaction to treatment with another monoclonal antibody
Has an active autoimmune disease that has required systemic treatment in past 2 years
Has an active infection requiring therapy
Has active, current pneumonitis, or a history of (non-infectious) pneumonitis that required steroids
Has had a prior stem cell or bone marrow transplant
Is positive for Human Immunodeficiency Virus (HIV) and/or Hepatitis B or C
Has known psychiatric disorder that would interfere with fulfilling the requirements of the study
Is a regular user of any illicit drugs or had a recent history of substance abuse
Has symptomatic ascites or pleural effusion
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study
Has clinically significant heart disease that affects normal activities
Has had major surgery (requiring at least a 3 day hospital stay) in the past 28 days
Has received a live vaccine within 30 days prior to first dose of study therapy

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

Arm/Group Information

ID	Title	Description
FG000	MK-1966 70 mg+SD-101 1 mg	Participants received a combination of MK-1966 70 mg intravenously (IV) (on Day 1 of each 3-week cycle for up to 8 cycles) and SD-101 1 mg intratumorally (IT) (on Days 1, 8 and 15 of Cycle 1, and then on Day 1 of up to 7 additional 3-week cycles) in Part A of the study. Participants were then to continue in one of two expansion cohorts (Part B or C) and were to receive up to 8 cycles of treatment on Day 1 of each 3-week cycle (approximately 24 weeks), but the study was terminated by the Sponsor prior to completion of Part A enrollment and prior to initiation of Parts B or C enrollment.
FG001	MK-1966 70 mg+SD-101 4 mg	Participants received a combination of MK-1966 70 mg IV (on Day 1 of each 3-week cycle for up to 8 cycles) and SD-101 4 mg IT (on Days 1, 8 and 15 of Cycle 1, and then on Day 1 of up to 7 additional 3-week cycles) in Part A of the study. Participants were then to continue in one of two expansion cohorts (Part B or C) and were to receive up to 8 cycles of treatment on Day 1 of each 3-week cycle (approximately 24 weeks), but the study was terminated by the Sponsor prior to completion of Part A enrollment and prior to initiation of Parts B or C enrollment.
FG002	MK-1966 210 mg+SD-101 4 mg	Participants received a combination of MK-1966 210 mg IV (on Day 1 of each 3-week cycle for up to 8 cycles) and SD-101 4 mg IT (on Days 1, 8 and 15 of Cycle 1, and then on Day 1 of up to 7 additional 3-week cycles) in Part A of the study. Participants were then to continue in one of two expansion cohorts (Part B or C) and were to receive up to 8 cycles of treatment on Day 1 of each 3-week cycle (approximately 24 weeks), but the study was terminated by the Sponsor prior to completion of Part A enrollment and prior to initiation of Parts B or C enrollment.
FG003	MK-1966 700 mg+SD-101 4 mg	Participants received a combination of MK-1966 700 mg IV (on Day 1 of each 3-week cycle for up to 8 cycles) and SD-101 4 mg IT (on Days 1, 8 and 15 of Cycle 1, and then on Day 1 of up to 7 additional 3-week cycles) in Part A of the study. Participants were to continue in one of two expansion cohorts (Part B or C) and were to receive up to 8 cycles of treatment on Day 1 of each 3-week cycle (approximately 24 weeks), but the study was terminated by the Sponsor prior to completion of Part A enrollment and prior to initiation of Parts B or C enrollment.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	MK-1966 70 mg+SD-101 1 mg	Participants received a combination of MK-1966 70 mg intravenously (IV) (on Day 1 of each 3-week cycle for up to 8 cycles) and SD-101 1 mg intratumorally (IT) (on Days 1, 8 and 15 of Cycle 1, and then on Day 1 of up to 7 additional 3-week cycles) in Part A of the study. Participants were then to continue in one of two expansion cohorts (Part B or C) and were to receive up to 8 cycles of treatment on Day 1 of each 3-week cycle (approximately 24 weeks), but the study was terminated by the Sponsor prior to completion of Part A enrollment and prior to initiation of Parts B or C enrollment.

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	Percentage of Participants With a Dose Limiting Toxicity (DLT)	The occurrence of any of the following toxicities during Cycle 1 (Days 1-21), if assessed by the Investigator to be possibly, probably or definitely related to MK-1966 or SD-101, was considered a DLT: Grade (Gr) 4 non-hematologic toxicity; Gr 4 hematologic toxicity lasting >7 days, except thrombocytopenia: Gr 4 thrombocytopenia of any duration; Gr 3 thrombocytopenia if associated with bleeding; Gr 3 non-hematologic toxicity lasting >3 days despite optimal supportive care; Any Gr 3 or Gr 4 non-hematologic laboratory abnormality, if: medical intervention is required OR abnormality leads to hospitalization OR abnormality persists for >1 week; Febrile neutropenia Gr 3 or Gr 4; Any drug-related AE which caused participant to discontinue study drug during Cycle 1 Gr 5 toxicity; or Delay in initiation of Cycle 2 for >2 weeks due to study drug-related toxicity. The percentage of participants who experienced a DLT during Cycle 1 is presented.	The DLT evaluable population consisted of all participants who completed study drug in Cycle 1 or discontinued study drug during Cycle 1 due to a DLT.	Posted		Number	80% Confidence Interval	Percentage of Participants		From time of first dose of study drug to the end of Cycle 1. Each cycle was 21 days. (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-1966 70 mg+SD-101 1 mg	Participants received a combination of MK-1966 70 mg intravenously (IV) (on Day 1 of each 3-week cycle for up to 8 cycles) and SD-101 1 mg intratumorally (IT) (on Days 1, 8 and 15 of Cycle 1, and then on Day 1 of up to 7 additional 3-week cycles) in Part A of the study. Participants were then to continue in one of two expansion cohorts (Part B or C) and were to receive up to 8 cycles of treatment on Day 1 of each 3-week cycle (approximately 24 weeks), but the study was terminated by the Sponsor prior to completion of Part A enrollment and prior to initiation of Parts B or C enrollment.