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NCT03189719

First-line Esophageal Carcinoma Study With Pembrolizumab Plus Chemo vs. Chemo (MK-3475-590/KEYNOTE-590)

Completed Phase 3 Results posted Last updated 15 October 2024
What this trial tests

Phase 3 trial testing Pembrolizumab in Esophageal Neoplasms in 749 participants. Completed in 10 July 2023.

Timeline
25 July 2017
Primary endpoint
2 July 2020
10 July 2023

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment749
Start date25 July 2017
Primary completion2 July 2020
Estimated completion10 July 2023
Sites189 locations across Hong Kong, Colombia, Japan, Malaysia, Taiwan, South Korea, Guatemala, Denmark

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Esophageal Neoplasms. 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.

Overall Survival (OS) in Participants With Esophageal Squamous Cell Carcinoma (ESCC) Whose Tumors Are Programmed Cell Death-Ligand 1 (PD-L1) Biomarker-Positive (Combined Positive Score [CPS] ≥10) Primary · Up to approximately 34 months

Overall survival was defined as the time from randomization 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. Per protocol, OS is reported here for all participants of the Intent-To-Treat (ITT) population (all randomized) who had ESCC and who were PD-L1 CPS ≥10.

GroupValue95% CI
Pembrolizumab + SOC13.911.1 – 17.7
Placebo + SOC8.87.8 – 10.5
OS in Participants With ESCC Primary · Up to approximately 34 months

Overall survival was defined as the time from randomization 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. Per protocol, OS is reported here for all participants of the ITT population (all randomized) who had ESCC.

GroupValue95% CI
Pembrolizumab + SOC12.610.2 – 14.3
Placebo + SOC9.88.6 – 11.1
OS in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) Primary · Up to approximately 34 months

Overall survival was defined as the time from randomization 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. Per protocol, OS is reported here for all participants of the ITT population (all randomized) who were PD-L1 CPS ≥10.

GroupValue95% CI
Pembrolizumab + SOC13.511.1 – 15.6
Placebo + SOC9.48.0 – 10.7
OS in All Participants Primary · Up to approximately 34 months

Overall survival was defined as the time from randomization 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. Per protocol, OS is reported here for all participants of the ITT population (all randomized).

GroupValue95% CI
Pembrolizumab + SOC12.410.5 – 14.0
Placebo + SOC9.88.8 – 10.8
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) As Assessed By Investigator in Participants With ESCC Primary · Up to approximately 34 months

PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS is reported here for all participa

GroupValue95% CI
Pembrolizumab + SOC6.36.2 – 6.9
Placebo + SOC5.85.0 – 6.1
PFS Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) Primary · Up to approximately 34 months

PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS is reported here for all participa

GroupValue95% CI
Pembrolizumab + SOC7.56.2 – 8.2
Placebo + SOC5.54.3 – 6.0
PFS Per RECIST 1.1 As Assessed By Investigator in All Participants Primary · Up to approximately 34 months

PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS is reported here for all participa

GroupValue95% CI
Pembrolizumab + SOC6.36.2 – 6.9
Placebo + SOC5.85.0 – 6.0
Objective Response Rate (ORR) Per RECIST 1.1 As Assessed By Investigator in All Participants Secondary · Up to approximately 34 months

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized).

GroupValue95% CI
Pembrolizumab + SOC45.039.9 – 50.2
Placebo + SOC29.324.7 – 34.1
ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) Secondary · Up to approximately 34 months

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized) who had ESCC and who were PD-L1 CPS ≥10.

GroupValue95% CI
Pembrolizumab + SOC51.042.6 – 59.5
Placebo + SOC28.020.8 – 36.1
ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Secondary · Up to approximately 34 months

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized) who had ESCC.

GroupValue95% CI
Pembrolizumab + SOC43.837.8 – 49.9
Placebo + SOC31.025.6 – 36.9
ORR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) Secondary · Up to approximately 34 months

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized) who were PD-L1 CPS ≥10.

GroupValue95% CI
Pembrolizumab + SOC51.143.7 – 58.5
Placebo + SOC26.920.8 – 33.7
Duration of Response (DOR) Per RECIST 1.1 As Assessed By Investigator in All Participants Secondary · Up to approximately 34 months

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by the investigator, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to

GroupValue95% CI
Pembrolizumab + SOC8.36.4 – 10.4
Placebo + SOC6.04.4 – 6.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 70 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pembrolizumab + SOC
Serious: 207/370 (56%)
Deaths: 331/373
Placebo + SOC
Serious: 204/370 (55%)
Deaths: 363/376

Serious adverse events (253 terms)

ReactionSystemPembrolizumab + SOCPlacebo + SOC
PneumoniaInfections and infestations
DysphagiaGastrointestinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Pneumonia aspirationInfections and infestations
Acute kidney injuryRenal and urinary disorders
AnaemiaBlood and lymphatic system disorders
Platelet count decreasedInvestigations
VomitingGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
DeathGeneral disorders
HypokalaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
FatigueGeneral disorders
Neutrophil count decreasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
NeutropeniaBlood and lymphatic system disorders
Oesophageal obstructionGastrointestinal disorders
StomatitisGastrointestinal disorders
PyrexiaGeneral disorders
SepsisInfections and infestations
Other adverse events (62 terms — click to expand)

ReactionSystemPembrolizumab + SOCPlacebo + SOC
NauseaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
Decreased appetiteMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
FatigueGeneral disorders
Neutrophil count decreasedInvestigations
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
StomatitisGastrointestinal disorders
White blood cell count decreasedInvestigations
NeutropeniaBlood and lymphatic system disorders
Weight decreasedInvestigations
Blood creatinine increasedInvestigations
HyponatraemiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
Mucosal inflammationGeneral disorders
Platelet count decreasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
AstheniaGeneral disorders
HiccupsRespiratory, thoracic and mediastinal disorders
AlopeciaSkin and subcutaneous tissue disorders
DysphagiaGastrointestinal disorders
PyrexiaGeneral disorders
HypoalbuminaemiaMetabolism and nutrition disorders
InsomniaPsychiatric disorders
MalaiseGeneral disorders
RashSkin and subcutaneous tissue disorders
HypothyroidismEndocrine disorders
DysgeusiaNervous system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Neuropathy peripheralNervous system disorders
TinnitusEar and labyrinth disorders
DizzinessNervous system disorders
Peripheral sensory neuropathyNervous system disorders
HypomagnesaemiaMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders

Most-reported serious reactions: Pneumonia, Dysphagia, Febrile neutropenia, Pneumonitis, Pneumonia aspiration, Acute kidney injury, Anaemia, Platelet count decreased.

Data from ClinicalTrials.gov NCT03189719 adverse events section.

Sponsor's own description

The purpose of this trial is to evaluate efficacy and safety of pembrolizumab plus standard of care (SOC) chemotherapy with cisplatin and 5-fluorouracil (5-FU) versus placebo plus SOC chemotherapy with cisplatin and 5-FU as first-line treatment in participants with locally advanced or metastatic esophageal carcinoma. The overall primary efficacy hypotheses are as follows: 1. In participants with esophageal squamous cell carcinoma (ESCC), participants whose tumors are programmed cell death-ligand 1 (PD-L1)-positive (defined as combined positive score \[CPS\] ≥10), ESCC participants whose tumors are PD-L1 positive (CPS ≥10), and in all participants, overall survival (OS) is superior with pembrolizumab plus SOC chemotherapy compared with placebo plus SOC chemotherapy. 2. In participants with ESCC, participants whose tumors are PD-L1 positive (CPS ≥10), and in all participants, progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by investigator is superior with pembrolizumab plus SOC chemotherapy compared with placebo plus SOC chemotherapy.

Publications & conference data

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

  1. Immune checkpoint inhibitors: recent progress and potential biomarkers.
    Darvin P, Toor SM, Sasidharan Nair V, Elkord E. · · 2018 · cited 1495× · PMID 30546008 · DOI 10.1038/s12276-018-0191-1
  2. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study.
    Sun JM, Shen L, Shah MA, Enzinger P, et al · · 2021 · cited 1143× · PMID 34454674 · DOI 10.1016/s0140-6736(21)01234-4
  3. Combination strategies with PD-1/PD-L1 blockade: current advances and future directions.
    Yi M, Zheng X, Niu M, Zhu S, et al · · 2022 · cited 1018× · PMID 35062949 · DOI 10.1186/s12943-021-01489-2
  4. Exploring treatment options in cancer: Tumor treatment strategies.
    Liu B, Zhou H, Tan L, Siu KTH, et al · · 2024 · cited 536× · PMID 39013849 · DOI 10.1038/s41392-024-01856-7
  5. 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
  6. Recent progress in multidisciplinary treatment for patients with esophageal cancer.
    Watanabe M, Otake R, Kozuki R, Toihata T, et al · · 2020 · cited 330× · PMID 31535225 · DOI 10.1007/s00595-019-01878-7
  7. Role of tumor microenvironment in cancer progression and therapeutic strategy.
    Wang Q, Shao X, Zhang Y, Zhu M, et al · · 2023 · cited 260× · PMID 36807772 · DOI 10.1002/cam4.5698
  8. Genetic, transcriptional and post-translational regulation of the programmed death protein ligand 1 in cancer: biology and clinical correlations.
    Zerdes I, Matikas A, Bergh J, Rassidakis GZ, et al · · 2018 · cited 223× · PMID 29765155 · DOI 10.1038/s41388-018-0303-3

Verify or expand the search:

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Trials by the same sponsor.

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