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NCT02559687

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

Completed Phase 2 Results posted Last updated 14 September 2022
What this trial tests

Phase 2 trial testing pembrolizumab in Esophageal Carcinoma in 121 participants. Completed in 29 October 2021.

Timeline
2 December 2015
Primary endpoint
30 July 2018
29 October 2021

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment121
Start date2 December 2015
Primary completion30 July 2018
Estimated completion29 October 2021

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Esophageal Carcinoma or Esophagogastric Junction Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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) Primary · Up to approximately 28 months

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 per protocol for the first course of treatment.

GroupValue95% CI
Pembrolizumab 200 mg9.95.2 – 16.7
Number of Participants Who Experienced an Adverse Event (AE) Secondary · Up to approximately 59 months

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. T

GroupValue95% CI
Pembrolizumab 200 mg116
Number of Participants That Discontinued Study Treatment Due to an AE Secondary · Up to approximately 24 months

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. T

GroupValue95% CI
Pembrolizumab 200 mg14
Duration of Response (DOR) According to RECIST 1.1 Assessed by BICR Secondary · Up to approximately 67 months

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 centra

GroupValue95% CI
Pembrolizumab 200 mg19.72.1 – 60.3
Progression Free Survival (PFS) According to RECIST 1.1 Assessed by BICR Secondary · Up to approximately 67 months

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 per protocol for the first course of treatment.

GroupValue95% CI
Pembrolizumab 200 mg2.01.9 – 2.1
Overall Survival (OS) Secondary · Up to approximately 67 months

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. OS was reported per protocol for the first course of treatment

GroupValue95% CI
Pembrolizumab 200 mg5.84.5 – 7.2

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 67 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pembrolizumab 200 mg First Course
Serious: 47/121 (39%)
Deaths: 116/121
Pembrolizumab 200 mg Second Course
Serious: 0/1 (0%)
Deaths: 0/1

Serious adverse events (50 terms)

ReactionSystemPembrolizumab 200 mg First…Pembrolizumab 200 mg Secon…
PneumoniaInfections and infestations
Pneumonia aspirationInfections and infestations
Acute kidney injuryRenal and urinary disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Atrial fibrillationCardiac disorders
HypopituitarismEndocrine disorders
Oesophageal stenosisGastrointestinal disorders
Diabetic ketoacidosisMetabolism and nutrition disorders
DeliriumPsychiatric disorders
Atrial flutterCardiac disorders
Tracheo-oesophageal fistulaCongenital, familial and genetic disorders
Inappropriate antidiuretic hormone secretionEndocrine disorders
Abdominal pain upperGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
HaematocheziaGastrointestinal disorders
Intestinal pseudo-obstructionGastrointestinal disorders
MelaenaGastrointestinal disorders
NauseaGastrointestinal disorders
OdynophagiaGastrointestinal disorders
PancreatitisGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
VomitingGastrointestinal disorders
MalaiseGeneral disorders
PyrexiaGeneral disorders
Other adverse events (41 terms — click to expand)

ReactionSystemPembrolizumab 200 mg First…Pembrolizumab 200 mg Secon…
FatigueGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
ConstipationGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Aspartate aminotransferase increasedInvestigations
PruritusSkin and subcutaneous tissue disorders
Alanine aminotransferase increasedInvestigations
HypothyroidismEndocrine disorders
Back painMusculoskeletal and connective tissue disorders
Oedema peripheralGeneral disorders
Blood alkaline phosphatase increasedInvestigations
InsomniaPsychiatric disorders
RashSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
AstheniaGeneral disorders
PneumoniaInfections and infestations
Blood bilirubin increasedInvestigations
DysphagiaGastrointestinal disorders
PyrexiaGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Dry mouthGastrointestinal disorders
Weight decreasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Neuropathy peripheralNervous system disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Oral painGastrointestinal disorders
HypertensionVascular disorders
Deafness neurosensoryEar and labyrinth disorders
Ear painEar and labyrinth disorders
PainGeneral disorders
Rotator cuff syndromeMusculoskeletal and connective tissue disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Pneumonia, Pneumonia aspiration, Acute kidney injury, Pneumonitis, Atrial fibrillation, Hypopituitarism, Oesophageal stenosis, Diabetic ketoacidosis.

Data from ClinicalTrials.gov NCT02559687 adverse events section.

Sponsor's own description

In this study participants with advanced/metastatic adenocarcinoma of the esophagus (EAC), squamous cell carcinoma of the esophagus (ESCC), or advanced/metastatic Siewert type I adenocarcinoma of the esophagogastric junction (EGJ), who had been previously treated with two standard therapies, will be treated with pembrolizumab.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Efficacy and Safety of Pembrolizumab for Heavily Pretreated Patients With Advanced, Metastatic Adenocarcinoma or Squamous Cell Carcinoma of the Esophagus: The Phase 2 KEYNOTE-180 Study.
    Shah MA, Kojima T, Hochhauser D, Enzinger P, et al · · 2019 · cited 378× · PMID 30570649 · DOI 10.1001/jamaoncol.2018.5441
  2. The immune landscape of esophageal cancer.
    Huang TX, Fu L. · · 2019 · cited 189× · PMID 31771653 · DOI 10.1186/s40880-019-0427-z
  3. Biomarkers for immunotherapy in bladder cancer: a moving target.
    Aggen DH, Drake CG. · · 2017 · cited 133× · PMID 29157296 · DOI 10.1186/s40425-017-0299-1
  4. Prognostic significance of tumor immune microenvironment and immunotherapy: Novel insights and future perspectives in gastric cancer.
    Lazăr DC, Avram MF, Romoșan I, Cornianu M, et al · · 2018 · cited 114× · PMID 30166856 · DOI 10.3748/wjg.v24.i32.3583
  5. Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy.
    Bhat AA, Nisar S, Maacha S, Carneiro-Lobo TC, et al · · 2021 · cited 106× · PMID 33390169 · DOI 10.1186/s12943-020-01294-3
  6. KEYNOTE-975 study design: a Phase III study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma.
    Shah MA, Bennouna J, Doi T, Shen L, et al · · 2021 · cited 98× · PMID 33533655 · DOI 10.2217/fon-2020-0969
  7. The promise of PD-1 inhibitors in gastro-esophageal cancers: microsatellite instability <i>vs</i>. PD-L1.
    Jin Z, Yoon HH. · · 2016 · cited 72× · PMID 27747091 · DOI 10.21037/jgo.2016.08.06
  8. Clinical and Recent Patents Applications of PD-1/PD-L1 Targeting Immunotherapy in Cancer Treatment-Current Progress, Strategy, and Future Perspective.
    Guo L, Wei R, Lin Y, Kwok HF. · · 2020 · cited 54× · PMID 32733486 · DOI 10.3389/fimmu.2020.01508

Verify or expand the search:

Other trials of pembrolizumab

Trials testing the same drug.

Other recruiting trials for Esophageal Carcinoma

Currently open trials in the same condition.

Other Merck Sharp & Dohme LLC trials

Trials by the same sponsor.

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