Clinical trial NCT03099161: Study of Preladenant (MK-3814) Alone and With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3814A-062)
Official title: A Phase Ib/II Study to Evaluate the Safety and Tolerability of Preladenant as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Neoplasm
Keywords: Advanced Solid Tumor
Programmed Cell Death Receptor 1 (PD-1)
Programmed Cell Death Receptor Ligand 1 (PD-L1)
PD1
PD-1
PDL1
PD-L1
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-04-04
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and preliminary efficacy of preladenant (MK-3814A) alone and in combination with pembrolizumab (MK-3475) (pembro) in participants with advanced solid tumors that have not responded to prior therapy. This study will be done in 2 parts. Part 1 will identify and confirm the recommended Phase 2 dose (RP2D) of preladenant when given alone or in combination with pembrolizumab. Part 2 of the study will determine the safety and efficacy of preladenant in combination with pembrolizumab at the RP2D in participants with select solid tumors .


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

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: Cycle 1 (up to 21 days)
measure: Number of Participants Who Experienced at Least One Adverse Event (AE)
timeFrame: Up tp approximately 8 months
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 8 months
Secondary outcomes:
measure: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to approximately 8 months
Other outcomes:
Locations:
city: Grand Rapids
country: United States
facility: START Midwest ( Site 0001)
state: Michigan
city: Toronto
country: Canada
facility: Princess Margaret Hospital ( Site 0010)
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital ( Site 0011)
state: Quebec
city: Haifa
country: Israel
facility: Rambam Health Care Campus ( Site 0020)
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center ( Site 0021)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: