Symptoms and General Pathology

All Conditions

Death

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

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.

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.

Administered as an oral capsule BID on Days 1 through 21 of each 21-day cycle

preladenant

Administered as IV infusion on Day 1 of each 21-day cycle

pembrolizumab

Medical Director

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 .

Study of Preladenant (MK-3814) Alone and With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3814A-062)

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

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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.

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.

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.

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.

Merck Sharp & Dohme LLC

The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.

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.

Preladenant 25 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.

Preladenant 50 mg BID

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.

Preladenant 25 mg BID + Pembrolizumab 200 mg

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Participants were assessed for ECOG PS: Grade 0: Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory \& able to carry out work of a light or sedentary nature; Grade 2: Ambulatory \& capable of all self-care but unable to carry out any work activities, up \& about \>50% of waking hours; Grade 3: Capable of only limited self-care, confined to bed or chair \>50% of waking hours; Grade 4: Completely disabled, cannot carry on any self-care, totally confined to bed or chair; or Grade 5: Dead.

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

Participants were required to have an advanced solid tumor that was unresponsive to 1 to 5 lines of prior therapy. The number of prior lines of therapy is presented.

Prior Line of Therapy

This study was terminated early because the data did not support the study endpoints.

Senior Vice President, Global Clinical Development

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

Number of Participants With Dose-limiting Toxicities (DLTs)

All participants who had a baseline scan that showed measurable disease by investigator assessment and who received at least one dose of study treatment

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

All participants who received at least one dose of study treatment

Number of Participants Who Experienced at Least One Adverse Event (AE)

Number of Participants Who Discontinued Study Treatment Due to an AE

Preladenant 25 mg Twice a Day (BID)

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.

Spots Global Cancer Trial Database for Study of Preladenant (MK-3814) Alone and With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3814A-062)

Trial Identification

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Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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