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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03099161
Recruitment Status : Terminated (The data did not support study endpoints)
First Posted : April 4, 2017
Results First Posted : June 5, 2019
Last Update Posted : June 5, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neoplasm
Interventions Drug: preladenant
Biological: pembrolizumab
Enrollment 10
Recruitment Details  
Pre-assignment Details This study was planned to have 2 parts: a dose escalation/confirmation phase (Part 1) and an expansion phase (Part 2). The expansion phase was not conducted due to early study termination.
Arm/Group Title Preladenant 25 mg Twice a Day (BID) Preladenant 50 mg BID Preladenant 25 mg BID + Pembrolizumab 200 mg
Hide Arm/Group Description 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. 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. 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.
Period Title: Overall Study
Started 3 4 3
Completed 0 0 0
Not Completed 3 4 3
Reason Not Completed
Adverse Event             0             0             2
Physician Decision             2             0             0
Progressive Disease             1             4             1
Arm/Group Title Preladenant 25 mg BID Preladenant 50 mg BID Preladenant 25 mg BID + Pembrolizumab 200 mg Total
Hide Arm/Group Description 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. 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 3 4 3 10
Hide Baseline Analysis Population Description
All enrolled participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 4 participants 3 participants 10 participants
61.3  (10.8) 40.3  (16.3) 41.3  (18.5) 46.9  (17.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 4 participants 3 participants 10 participants
Female
2
  66.7%
2
  50.0%
1
  33.3%
5
  50.0%
Male
1
  33.3%
2
  50.0%
2
  66.7%
5
  50.0%
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 4 participants 3 participants 10 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
3
 100.0%
4
 100.0%
3
 100.0%
10
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: The race of participants is presented.
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 4 participants 3 participants 10 participants
ECOG PS=0
2
  66.7%
2
  50.0%
2
  66.7%
6
  60.0%
ECOG PS=1
1
  33.3%
2
  50.0%
1
  33.3%
4
  40.0%
[1]
Measure Description: 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.
Prior Line of Therapy   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 4 participants 3 participants 10 participants
First Line
2
  66.7%
2
  50.0%
0
   0.0%
4
  40.0%
Second Line
0
   0.0%
2
  50.0%
3
 100.0%
5
  50.0%
Third Line
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Fourth Line
1
  33.3%
0
   0.0%
0
   0.0%
1
  10.0%
Fifth Line
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: 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.
1.Primary Outcome
Title Number of Participants With Dose-limiting Toxicities (DLTs)
Hide Description 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.
Time Frame Cycle 1 (up to 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Preladenant 25 mg BID Preladenant 50 mg BID Preladenant 25 mg BID + Pembrolizumab 200 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 3 4 3
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
2.Primary Outcome
Title Number of Participants Who Experienced at Least One Adverse Event (AE)
Hide Description 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.
Time Frame Up tp approximately 8 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment
Arm/Group Title Preladenant 25 mg BID Preladenant 50 mg BID Preladenant 25 mg BID + Pembrolizumab 200 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 3 4 3
Measure Type: Count of Participants
Unit of Measure: Participants
3
 100.0%
4
 100.0%
3
 100.0%
3.Primary Outcome
Title Number of Participants Who Discontinued Study Treatment Due to an AE
Hide Description 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.
Time Frame Up to approximately 8 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment
Arm/Group Title Preladenant 25 mg BID Preladenant 50 mg BID Preladenant 25 mg BID + Pembrolizumab 200 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 3 4 3
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
2
  66.7%
4.Secondary Outcome
Title Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Hide Description 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.
Time Frame Up to approximately 8 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who had a baseline scan that showed measurable disease by investigator assessment and who received at least one dose of study treatment
Arm/Group Title Preladenant 25 mg BID Preladenant 50 mg BID Preladenant 25 mg BID + Pembrolizumab 200 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 3 4 3
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
0.0
(0.0 to 70.8)
0.0
(0.0 to 60.2)
0.0
(0.0 to 70.8)
Time Frame Up to approximately 8 months
Adverse Event Reporting Description 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.
 
Arm/Group Title Preladenant 25 mg BID Preladenant 50 mg BID Preladenant 25 mg BID + Pembrolizumab 200 mg
Hide Arm/Group Description 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. 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. 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.
All-Cause Mortality
Preladenant 25 mg BID Preladenant 50 mg BID Preladenant 25 mg BID + Pembrolizumab 200 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/3 (66.67%)      2/4 (50.00%)      0/3 (0.00%)    
Hide Serious Adverse Events
Preladenant 25 mg BID Preladenant 50 mg BID Preladenant 25 mg BID + Pembrolizumab 200 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/3 (66.67%)      1/4 (25.00%)      2/3 (66.67%)    
Endocrine disorders       
Inappropriate antidiuretic hormone secretion  1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0
Gastrointestinal disorders       
Dysphagia  1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0
Intestinal obstruction  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0
Infections and infestations       
Urinary tract infection  1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/3 (33.33%)  2
Investigations       
Liver function test increased  1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/3 (66.67%)  2
Renal and urinary disorders       
Kidney enlargement  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Preladenant 25 mg BID Preladenant 50 mg BID Preladenant 25 mg BID + Pembrolizumab 200 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      4/4 (100.00%)      3/3 (100.00%)    
Blood and lymphatic system disorders       
Anaemia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/3 (33.33%)  1
Ear and labyrinth disorders       
Vertigo  1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0
Eye disorders       
Vision blurred  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0
Gastrointestinal disorders       
Abdominal hernia  1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0
Abdominal pain  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0
Constipation  1  1/3 (33.33%)  1 2/4 (50.00%)  3 1/3 (33.33%)  1
Diarrhoea  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0
Intra-abdominal fluid collection  1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0
Mouth ulceration  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0
Nausea  1  1/3 (33.33%)  1 2/4 (50.00%)  2 0/3 (0.00%)  0
Oesophageal pain  1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0
Rectal haemorrhage  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0
Vomiting  1  0/3 (0.00%)  0 2/4 (50.00%)  3 0/3 (0.00%)  0
Dyschezia  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0
General disorders       
Asthenia  1  1/3 (33.33%)  1 2/4 (50.00%)  2 0/3 (0.00%)  0
Fatigue  1  1/3 (33.33%)  1 2/4 (50.00%)  2 1/3 (33.33%)  1
Oedema peripheral  1  2/3 (66.67%)  2 0/4 (0.00%)  0 0/3 (0.00%)  0
Pyrexia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/3 (33.33%)  1
Injury, poisoning and procedural complications       
Stoma site haemorrhage  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0
Investigations       
Alanine aminotransferase increased  1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/3 (33.33%)  1
Aspartate aminotransferase increased  1  0/3 (0.00%)  0 0/4 (0.00%)  0 2/3 (66.67%)  2
Weight decreased  1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0
Metabolism and nutrition disorders       
Decreased appetite  1  0/3 (0.00%)  0 2/4 (50.00%)  2 0/3 (0.00%)  0
Hypokalaemia  1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/3 (33.33%)  1
Muscular weakness  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0
Myalgia  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0
Nervous system disorders       
Dizziness  1  0/3 (0.00%)  0 1/4 (25.00%)  1 1/3 (33.33%)  1
Memory impairment  1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0
Presyncope  1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Cough  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0
Dyspnoea  1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0
Pleural effusion  1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0
Skin and subcutaneous tissue disorders       
Acne  1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/3 (33.33%)  1
Night sweats  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0
Vascular disorders       
Deep vein thrombosis  1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0
Hot flush  1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/3 (33.33%)  1
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
This study was terminated early because the data did not support the study endpoints.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03099161    
Other Study ID Numbers: 3814A-062
MK-3814A-062 ( Other Identifier: Merck Protocol Number )
First Submitted: March 30, 2017
First Posted: April 4, 2017
Results First Submitted: September 7, 2018
Results First Posted: June 5, 2019
Last Update Posted: June 5, 2019