Study of Preladenant (MK-3814) Alone and With Pembrolizum... | NCT03099161

NCT03099161

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-3814A-062	Other Identifier	Merck Protocol Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Preladenant 25 mg Twice a Day (BID)	Experimental	During an initial dose evaluation phase, participants received 25 mg of preladenant orally twice a day (BID) on Days 1 through 21 of each 21-day cycle (for a maximum of 35 cycles) until the RP2D could be established. The RP2D was to be established based on the number of dose limiting toxicities (DLTs) at each dose level administered. Participants continued receiving 25 mg of preladenant BID on Days 1 through 21 of each infusion cycle until discontinuation or receiving a maximum of 35 cycles.	Drug: preladenant
Preladenant 50 mg BID	Experimental	During an initial dose evaluation phase, participants received 50 mg of preladenant orally BID on Days 1 through 21 of each 21-day cycle (for a maximum of 35 cycles) until the RP2D could be established. The RP2D was established based on the number of DLTs at each dose level administered. Participants continued receiving 50 mg of preladenant BID on Days 1 through 21 of each infusion cycle until discontinuation or receiving a maximum of 35 cycles.	Drug: preladenant
Preladenant + Pembrolizumab	Experimental	During an initial dose evaluation phase, participants received 25 mg of preladenant administered orally BID on Days 1 through 21 in combination with 200 mg pembrolizumab administered as an intravenous (IV) infusion on Day 1 of each 21-day cycle (for a maximum of 35 cycles). Participants continued receiving preladenant 25 mg BID in combination with 200 mg pembrolizumab for each infusion cycle until discontinuation or receiving a maximum of 35 cycles.	Drug: preladenant Biological: pembrolizumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
preladenant	Drug	Administered as an oral capsule BID on Days 1 through 21 of each 21-day cycle	Preladenant + Pembrolizumab Preladenant 25 mg Twice a Day (BID)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Dose-limiting Toxicities (DLTs)	DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. A DLT was defined as any of the following events: Grade (Gr) 4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days; Gr 4 thrombocytopenia of any duration; Gr 3 thrombocytopenia with bleeding; Gr 3 non-hematologic toxicity (not laboratory) lasting >3 days despite optimal supportive care; Gr 3 or Gr 4 non-hematologic laboratory value requiring treatment, hospitalization, or persisting for >72 hours; alanine aminotransferase (ALT) or aspartate aminotransferase(AST) >3X upper limit of normal (ULN) WITH total bilirubin >2X ULN with no elevation in alkaline phosphatase (<2X ULN); Febrile neutropenia Gr 3 or 4; discontinuation during Cycle 1 or a >2 week delay in initiating Cycle 2 due to treatment-related toxicity; Missing >25% of preladenant doses as a result of adverse events during Cycle 1; or Gr 5 toxicity.	Cycle 1 (up to 21 days)
Number of Participants Who Experienced at Least One Adverse Event (AE)	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. The number of participants who experienced at least one AE is presented.	Up tp approximately 8 months
Number of Participants Who Discontinued Study Treatment Due to an AE	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. The number of participants who discontinued study treatment due to an AE is presented.

Secondary Outcomes

Measure	Description	Time Frame
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 per investigator review. The ORR per RECIST 1.1 for participants is presented.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has a histologically- or pathologically-documented, locally-advanced or metastatic solid tumor for which standard therapy, either does not exist or has been proven ineffective, intolerable or refused by the participant. Each participant must have received at least one and up to five prior lines of cancer treatment regimens, excluding neo-adjuvant, adjuvant, maintenance treatment and surgery
Has provided a tumor tissue sample (archival or newly obtained core or excisional biopsy of a tumor lesion)
Has measurable disease per RECIST 1.1
Has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Females must not be pregnant
Female and male participants of reproductive potential must agree to use adequate contraception starting from the first dose of study therapy, throughout the study period, and for up to 120 days after the last dose of study therapy

Exclusion Criteria:

Has disease that is suitable for local treatment administered with curative intent
Has received previous treatment with an immunomodulatory agent (e.g, anti- Programmed Cell Death Receptor 1/ Programmed Cell Death Receptor Ligand 1 or anti-cytotoxic T-lymphocyte-associated antigen-4) and was discontinued from treatment due to a Grade 3 or higher immune-related adverse event
Has received previous treatment with an adenosine A2a receptor antagonist (e.g. CPI-444, HTL1071, PBF-509)
Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks of the first dose of study therapy, or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) grade 1 or better from any adverse event
Is currently participating or has participated in a study with an investigational agent or using an investigational device within 28 days of the first dose of study therapy
Is currently taking or has taken drugs that interfere with Cytochrome P450 (CYP)3A4 or CYP2C8 or grapefruit and star fruit in diet within 14 days of the first dose of study therapy
Is currently taking or has taken proton pump inhibitors within 5 days of the first dose of study therapy
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of the first dose of study therapy
Is expected to require any other form of systemic or localized antineoplastic therapy while on study
Has a history of a second malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years
Has clinically active central nervous system metastases and/or carcinomatous meningitis
History of a severe hypersensitivity reaction to treatment with the monoclonal antibody/components of the study drug
Has an active infection requiring therapy
History of interstitial lung disease
History of (non-infectious) pneumonitis that required steroids or current pneumonitis
History of active tuberculosis
Has an active autoimmune disease that has required systemic treatment in the past 2 years
Has received a live-virus vaccine within 30 days of the first dose of study therapy
Has known Human Immunodeficiency Virus (HIV) (HIV 1 or 2 antibodies) and/or known active and acute Hepatitis B or C infections
Has known psychiatric or substance abuse disorders that would interfere with the ability to cooperate with the requirements of the study
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
Has not fully recovered from any effects of major surgery without significant detectable infection
Has had surgery that required general anesthesia within 2 weeks of the first dose of study therapy
Has had surgery that required regional/epidural anesthesia within 72 hours of the first dose of study therapy

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

Facility	Status	City	State	ZIP	Country	Contacts
START Midwest ( Site 0001)		Grand Rapids	Michigan	49546	United States
Princess Margaret Hospital ( Site 0010)

Arm/Group Information

ID	Title	Description
FG000	Preladenant 25 mg Twice a Day (BID)	Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.
FG001	Preladenant 50 mg BID	Participants received 50 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.
FG002	Preladenant 25 mg BID + Pembrolizumab 200 mg	Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 and pembrolizumab 200 mg administered by intravenous (IV) infusion on Day 1 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.

ID	Title	Description
BG000	Preladenant 25 mg BID	Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.
BG001	Preladenant 50 mg BID

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 With Dose-limiting Toxicities (DLTs)	DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. A DLT was defined as any of the following events: Grade (Gr) 4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days; Gr 4 thrombocytopenia of any duration; Gr 3 thrombocytopenia with bleeding; Gr 3 non-hematologic toxicity (not laboratory) lasting >3 days despite optimal supportive care; Gr 3 or Gr 4 non-hematologic laboratory value requiring treatment, hospitalization, or persisting for >72 hours; alanine aminotransferase (ALT) or aspartate aminotransferase(AST) >3X upper limit of normal (ULN) WITH total bilirubin >2X ULN with no elevation in alkaline phosphatase (<2X ULN); Febrile neutropenia Gr 3 or 4; discontinuation during Cycle 1 or a >2 week delay in initiating Cycle 2 due to treatment-related toxicity; Missing >25% of preladenant doses as a result of adverse events during Cycle 1; or Gr 5 toxicity.	All participants who received at least one dose of study treatment in Cycle 1 (21-day Cycle) and were observed for safety or experienced a DLT during Cycle 1	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	Preladenant 25 mg BID	Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Inappropriate antidiuretic hormone secretion	Endocrine 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

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

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	Mar 30, 2017	Sep 7, 2018	Prot_SAP_000.pdf

ID	Term
D009369	Neoplasms
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body

ID	Term
C539997	2-(2-furanyl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)-1-piperazinyl)ethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidine-5-amine
C582435	pembrolizumab

ID	Title	Description
OG000	Preladenant 25 mg BID	Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.
OG001	Preladenant 50 mg BID	Participants received 50 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.
OG002	Preladenant 25 mg BID + Pembrolizumab 200 mg	Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 and pembrolizumab 200 mg administered by IV infusion on Day 1 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.