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Study of Pembrolizumab (MK-3475) in Previously-Treated Participants With Advanced Carcinoma of the Esophagus or Esophagogastric Junction (MK-3475-180/KEYNOTE-180)

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: NCT02559687
Recruitment Status : Completed
First Posted : September 24, 2015
Results First Posted : July 17, 2019
Last Update Posted : November 11, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Esophageal Carcinoma
Esophagogastric Junction Carcinoma
Intervention Biological: pembrolizumab
Enrollment 121
Recruitment Details  
Pre-assignment Details Of 185 participants screened for inclusion, 121 were enrolled and received treatment.
Arm/Group Title Pembrolizumab 200 mg
Hide Arm/Group Description Participants receive pembrolizumab 200 mg, intravenously (IV), every 3 weeks (Q3W) for up to 35 treatments (approximately 2 years).
Period Title: Overall Study
Started 121
Completed 0
Not Completed 121
Reason Not Completed
Death             103
Withdrawal by Subject             4
Ongoing Follow-Up             14
Arm/Group Title Pembrolizumab 200 mg
Hide Arm/Group Description Participants receive pembrolizumab 200 mg IV Q3W for up to 35 treatments (approximately 2 years).
Overall Number of Baseline Participants 121
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 121 participants
63.5  (10.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants
Female
21
  17.4%
Male
100
  82.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants
Hispanic or Latino
2
   1.7%
Not Hispanic or Latino
108
  89.3%
Unknown or Not Reported
11
   9.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants
American Indian or Alaska Native
0
   0.0%
Asian
42
  34.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
   1.7%
White
71
  58.7%
More than one race
0
   0.0%
Unknown or Not Reported
6
   5.0%
1.Primary Outcome
Title Objective Response Rate (ORR) According to Response Evaluation Criteria for Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR)
Hide Description ORR was defined as the percentage of participants who have 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) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a CR or PR based on modified RECIST 1.1 was reported.
Time Frame Up to approximately 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
All allocated participants who received at least 1 dose of study treatment.
Arm/Group Title Pembrolizumab 200 mg
Hide Arm/Group Description:
Participants receive pembrolizumab 200 mg IV Q3W for up to 35 treatments (approximately 2 years).
Overall Number of Participants Analyzed 121
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
9.9
(5.2 to 16.7)
2.Secondary Outcome
Title Number of Participants Who Experienced an 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 unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an adverse event. The number of participants who experienced ≥1 AE was reported.
Time Frame Up to approximately 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
All allocated participants who received at least 1 dose of study treatment.
Arm/Group Title Pembrolizumab 200 mg
Hide Arm/Group Description:
Participants receive pembrolizumab 200 mg IV Q3W for up to 35 treatments (approximately 2 years).
Overall Number of Participants Analyzed 121
Measure Type: Count of Participants
Unit of Measure: Participants
116
  95.9%
3.Secondary Outcome
Title Number of Participants That 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 unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an adverse event. The number of participants that discontinued study treatment due to an AE was reported.
Time Frame Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
All allocated participants who received at least 1 dose of study treatment.
Arm/Group Title Pembrolizumab 200 mg
Hide Arm/Group Description:
Participants receive pembrolizumab 200 mg IV Q3W for up to 35 treatments (approximately 2 years).
Overall Number of Participants Analyzed 121
Measure Type: Count of Participants
Unit of Measure: Participants
13
  10.7%
4.Secondary Outcome
Title Duration of Response (DOR) According to RECIST 1.1 Assessed by BICR
Hide Description For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. DOR assessments were based on blinded central imaging review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR was reported.
Time Frame Up to approximately 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
All allocated participants who received at least 1 dose of study treatment and who experienced a confirmed CR or confirmed PR.
Arm/Group Title Pembrolizumab 200 mg
Hide Arm/Group Description:
Participants receive pembrolizumab 200 mg IV Q3W for up to 35 treatments (approximately 2 years).
Overall Number of Participants Analyzed 12
Median (Full Range)
Unit of Measure: Months
NA [1] 
(2.1 to NA)
[1]
NA=The median of DOR and the upper range of DOR are not reached (no progressive disease by time of last disease assessment).
5.Secondary Outcome
Title Progression Free Survival (PFS) According to RECIST 1.1 Assessed by BICR
Hide Description PFS was defined as the time from first day of study treatment to the first documented PD or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of ≥1 new lesions was also considered PD. PFS as assessed by blinded independent central review per RECIST 1.1 was reported.
Time Frame Up to approximately 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
All allocated participants who received at least 1 dose of study treatment.
Arm/Group Title Pembrolizumab 200 mg
Hide Arm/Group Description:
Participants receive pembrolizumab 200 mg IV Q3W for up to 35 treatments (approximately 2 years).
Overall Number of Participants Analyzed 121
Median (95% Confidence Interval)
Unit of Measure: Months
2.0
(1.9 to 2.1)
6.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from first day of study treatment to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up.
Time Frame Up to approximately 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
All allocated participants who received at least 1 dose of study treatment.
Arm/Group Title Pembrolizumab 200 mg
Hide Arm/Group Description:
Participants receive pembrolizumab 200 mg IV Q3W for up to 35 treatments (approximately 2 years).
Overall Number of Participants Analyzed 121
Median (95% Confidence Interval)
Unit of Measure: Months
5.8
(4.5 to 7.2)
Time Frame Up to approximately 28 months
Adverse Event Reporting Description

All-Cause Mortality was reported for all allocated participants.

Serious AEs and Other AEs were reported for all allocated participants who received at least 1 dose of study treatment. Per protocol, disease progression of cancer on study was not considered an AE 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 as AEs.
 
Arm/Group Title Pembrolizumab 200 mg
Hide Arm/Group Description Participants receive pembrolizumab 200 mg IV Q3W for up to 35 treatments (approximately 2 years).
All-Cause Mortality
Pembrolizumab 200 mg
Affected / at Risk (%)
Total   107/121 (88.43%)    
Hide Serious Adverse Events
Pembrolizumab 200 mg
Affected / at Risk (%) # Events
Total   47/121 (38.84%)    
Cardiac disorders   
Atrial fibrillation † 1  2/121 (1.65%)  2
Atrial flutter † 1  1/121 (0.83%)  1
Congenital, familial and genetic disorders   
Tracheo-oesophageal fistula † 1  1/121 (0.83%)  1
Endocrine disorders   
Hypopituitarism † 1  2/121 (1.65%)  2
Inappropriate antidiuretic hormone secretion † 1  1/121 (0.83%)  1
Gastrointestinal disorders   
Abdominal pain upper † 1  1/121 (0.83%)  1
Diarrhoea † 1  1/121 (0.83%)  2
Gastrointestinal haemorrhage † 1  1/121 (0.83%)  1
Haematochezia † 1  1/121 (0.83%)  1
Intestinal pseudo-obstruction † 1  1/121 (0.83%)  1
Melaena † 1  1/121 (0.83%)  1
Nausea † 1  1/121 (0.83%)  1
Odynophagia † 1  1/121 (0.83%)  1
Oesophageal stenosis † 1  2/121 (1.65%)  2
Pancreatitis † 1  1/121 (0.83%)  1
Small intestinal obstruction † 1  1/121 (0.83%)  1
Vomiting † 1  1/121 (0.83%)  1
General disorders   
Malaise † 1  1/121 (0.83%)  1
Pyrexia † 1  1/121 (0.83%)  1
Infections and infestations   
Cellulitis † 1  1/121 (0.83%)  1
Herpes zoster † 1  1/121 (0.83%)  1
Lung infection † 1  3/121 (2.48%)  3
Pneumonia † 1  13/121 (10.74%)  14
Sepsis † 1  1/121 (0.83%)  1
Injury, poisoning and procedural complications   
Infusion related reaction † 1  1/121 (0.83%)  1
Limb injury † 1  1/121 (0.83%)  1
Pubis fracture † 1  1/121 (0.83%)  1
Metabolism and nutrition disorders   
Decreased appetite † 1  1/121 (0.83%)  1
Diabetic ketoacidosis † 1  2/121 (1.65%)  2
Failure to thrive † 1  1/121 (0.83%)  1
Hypercalcaemia † 1  1/121 (0.83%)  1
Malnutrition † 1  1/121 (0.83%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia † 1  1/121 (0.83%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Tumour necrosis † 1  1/121 (0.83%)  1
Nervous system disorders   
Cerebrovascular accident † 1  1/121 (0.83%)  1
Psychiatric disorders   
Anxiety † 1  1/121 (0.83%)  1
Delirium † 1  2/121 (1.65%)  2
Renal and urinary disorders   
Acute kidney injury † 1  4/121 (3.31%)  4
Nephritis † 1  1/121 (0.83%)  1
Urinary retention † 1  1/121 (0.83%)  1
Respiratory, thoracic and mediastinal disorders   
Choking † 1  1/121 (0.83%)  1
Chronic obstructive pulmonary disease † 1  1/121 (0.83%)  1
Dyspnoea † 1  1/121 (0.83%)  1
Pneumonia aspiration † 1  5/121 (4.13%)  5
Pneumonitis † 1  3/121 (2.48%)  3
Pneumothorax † 1  1/121 (0.83%)  1
Pulmonary embolism † 1  1/121 (0.83%)  1
Vascular disorders   
Deep vein thrombosis † 1  1/121 (0.83%)  1
Hypotension † 1  1/121 (0.83%)  1
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%
Pembrolizumab 200 mg
Affected / at Risk (%) # Events
Total   104/121 (85.95%)    
Blood and lymphatic system disorders   
Anaemia † 1  18/121 (14.88%)  22
Endocrine disorders   
Hypothyroidism † 1  11/121 (9.09%)  13
Gastrointestinal disorders   
Abdominal pain † 1  9/121 (7.44%)  9
Constipation † 1  23/121 (19.01%)  24
Diarrhoea † 1  18/121 (14.88%)  22
Dry mouth † 1  7/121 (5.79%)  7
Dysphagia † 1  8/121 (6.61%)  8
Nausea † 1  22/121 (18.18%)  26
Vomiting † 1  19/121 (15.70%)  25
General disorders   
Asthenia † 1  9/121 (7.44%)  10
Fatigue † 1  34/121 (28.10%)  37
Oedema peripheral † 1  10/121 (8.26%)  11
Pyrexia † 1  9/121 (7.44%)  14
Investigations   
Alanine aminotransferase increased † 1  12/121 (9.92%)  13
Aspartate aminotransferase increased † 1  13/121 (10.74%)  14
Blood alkaline phosphatase increased † 1  10/121 (8.26%)  11
Blood bilirubin increased † 1  9/121 (7.44%)  9
Weight decreased † 1  7/121 (5.79%)  8
Metabolism and nutrition disorders   
Decreased appetite † 1  23/121 (19.01%)  23
Hypokalaemia † 1  7/121 (5.79%)  10
Hyponatraemia † 1  7/121 (5.79%)  8
Musculoskeletal and connective tissue disorders   
Back pain † 1  12/121 (9.92%)  13
Myalgia † 1  8/121 (6.61%)  8
Nervous system disorders   
Neuropathy peripheral † 1  7/121 (5.79%)  7
Psychiatric disorders   
Insomnia † 1  10/121 (8.26%)  10
Respiratory, thoracic and mediastinal disorders   
Cough † 1  24/121 (19.83%)  26
Dyspnoea † 1  16/121 (13.22%)  19
Skin and subcutaneous tissue disorders   
Pruritus † 1  13/121 (10.74%)  13
Rash † 1  10/121 (8.26%)  13
1
Term from vocabulary, MedDRA 21.0
†
Indicates events were collected by systematic assessment
[Not Specified]
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
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT02559687    
Other Study ID Numbers: 3475-180
2015-002427-26 ( EudraCT Number )
163188 ( Registry Identifier: JAPIC-CTI )
MK-3475-180 ( Other Identifier: Merck )
KEYNOTE -180 ( Other Identifier: Merck )
First Submitted: September 23, 2015
First Posted: September 24, 2015
Results First Submitted: June 27, 2019
Results First Posted: July 17, 2019
Last Update Posted: November 11, 2021