Neoplasms

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Esophageal Neoplasms

Adenocarcinoma

Esophageal Squamous Cell Carcinoma

Death

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Paclitaxel

Pembrolizumab

Docetaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to \~2 years). Participants who complete the first course of up to 35 administrations of pembrolizumab (\~2 years) but progress after discontinuation, may be eligible for a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 of each 3-week cycle for up to 17 cycles (up to \~1 year).

Participants receive Investigator's choice of chemotherapy: paclitaxel 80-100 mg/m\^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m\^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m\^2 IV on Day 1 of every 14-day (2-week) cycle (up to \~2 years).

pembrolizumab

paclitaxel

docetaxel

irinotecan

Medical Director

In the China extension study, Chinese participants with advanced or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the esophagogastric junction (EGJ) that has progressed after first-line standard therapy will be randomized to receive either single agent pembrolizumab or the Investigator's choice of chemotherapy with paclitaxel, docetaxel, or irinotecan.

The primary extension study hypothesis is that treatment with pembrolizumab will prolong overall survival (OS) as compared to treatment with chemotherapy.

The China extension study will include participants previously enrolled in China in the global study for MK-3475-181 (NCT02564263) plus those enrolled during the China extension enrollment period.

Per protocol, response/progression or adverse events during the second pembrolizumab course will not be counted towards efficacy outcome measures or safety outcome measures.

Study of Pembrolizumab (MK-3475) Versus Investigator's Choice of Chemotherapy for Participants With Advanced Esophageal/Esophagogastric Junction Carcinoma That Progressed After First-Line Therapy (MK-3475-181/KEYNOTE-181)-China Extension Study

A Phase III Randomized Open-Label Study of Single Agent Pembrolizumab vs Physicians' Choice of Single Agent Docetaxel, Paclitaxel, or Irinotecan in Subjects With Advanced/Metastatic Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus That Have Progressed After First-Line Standard Therapy (KEYNOTE-181)

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

OS was defined as the time from randomization to death due to any cause. Median OS for the first pembrolizumab course in all participants is presented.

OS was defined as the time from randomization to death due to any cause. Median OS for the first pembrolizumab course in participants with a PD-L1 CPS ≥10 is presented.

OS was defined as the time from randomization to death due to any cause. Median OS for the first pembrolizumab course in participants with SCC of the esophagus is presented.

ORR was defined as the percentage of participants 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) as assessed using RECIST 1.1 by central imaging vendor review. The percentage of all participants who experienced a CR or PR for the first pembrolizumab course is presented.

ORR was defined as the percentage of participants 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) as assessed using RECIST 1.1 by central imaging vendor review. The percentage of participants with a PD-L1 CPS ≥10 who experienced a CR or PR for the first pembrolizumab course is presented.

ORR was defined as the percentage of participants 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) as assessed using RECIST 1.1 by central imaging vendor review. The percentage of participants with SCC of the esophagus who experienced a CR or PR for the first pembrolizumab course is presented.

PFS was defined as the time from randomization to the first documented progressive disease (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. The appearance of ≥1 new lesions was also considered PD. Median PFS for the first pembrolizumab course as assessed by central imaging vendor review per RECIST 1.1 in all participants is presented.

PFS was defined as the time from randomization to the first documented progressive disease (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. The appearance of ≥1 new lesions was also considered PD. Median PFS for the first pembrolizumab course as assessed by central imaging vendor review per RECIST 1.1 is presented for participants with a PD-L1 CPS ≥10.

PFS was defined as the time from randomization to the first documented progressive disease (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. The appearance of ≥1 new lesions was also considered PD. Median PFS for the first pembrolizumab course as assessed by central imaging vendor review per RECIST 1.1 is presented for participants with SCC of the esophagus.

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. The number of participants who experienced ≥1 AE for the first pembrolizumab course are presented.

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE for the first pembrolizumab course are presented.

Merck Sharp & Dohme LLC

All-Cause Mortality (ACM): All randomized participants. Safety: All randomized participants who got ≥1 dose of study treatment.

Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" \& "Disease progression" unrelated to study drug are excluded as AEs.

Participants who received a second course of pembrolizumab per protocol were monitored for ACM and AEs separately.

Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to \~2 years).

Pembrolizumab First Course

Participants received Investigator's choice of chemotherapy for up to \~2 years: paclitaxel 80-100 mg/m\^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m\^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m\^2 IV on Day 1 of every 14-day (2-week) cycle.

Chemotherapy

Participants who completed the first course of up to 35 administrations of pembrolizumab (\~2 years) but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 of each 3-week cycle for up to 17 cycles (up to \~1 year).

Pembrolizumab Second Course

Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of every 21-day (3 week) cycle for up to 35 administrations (up to \~2 years). Participants who completed the first course of up to 35 administrations of pembrolizumab (\~2 years) but progressed after discontinuation, were eligible for a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 of each 3-week cycle for up to 17 cycles (up to \~1 year).

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

PD-L1 CPS ≥10

PD-L1 CPS <10

Not Evaluable

Participants were assessed for their PD-L1 tumor expression levels by immunohistochemistry assay on tumor tissue from a newly obtained biopsy. PD-L1 CPS was calculated as the number of PD-L1 positive cells (tumor cells, macrophages, lymphocytes) divided by the total tumor cells and is expressed as a percentage. Participants were classified based on their PD-L1 tumor status as being either PD-L1 CPS ≥10 or PD-L1 CPS \<10.

Programmed Death-Ligand 1 (PD-L1) Status: Combined Positive Score (CPS)

Squamous cell carcinoma

Adenocarcinoma of esophagus & EGJ Siewert type I

Participants were classified based on their tumor histology (cell type) as either having squamous cell carcinoma or having adenocarcinoma of esophagus and esophagogastric junction (EGJ) Siewert type I.

Tumor Histology

Senior Vice President, Global Clinical Development

Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of every 21-day (3 week) cycle for up to 35 administrations (up to \~2 years).

The efficacy analysis population consisted of all randomized participants. Participants were included in the treatment group to which they were randomized.

Overall Survival (OS) in All Participants

The efficacy analysis population consisted of all randomized participants with a PD-L1 CPS ≥10. Participants were included in the treatment group to which they were randomized.

Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)

The efficacy analysis population consisted of all randomized participants with SCC of the esophagus. Participants were included in the treatment group to which they were randomized.

Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus

The efficacy analysis population consisted of all randomized participants who experienced a confirmed response (CR or PR). Participants were included in the treatment group to which they were randomized.

Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants

The efficacy analysis population consisted of all randomized participants with a PD-L1 CPS ≥10 who experienced a confirmed response (CR or PR). Participants were included in the treatment group to which they were randomized.

Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)

The efficacy analysis population consisted of all randomized participants with SCC of the esophagus who experienced a confirmed response (CR or PR). Participants were included in the treatment group to which they were randomized.

Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus

Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants

Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)

Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus

All randomized participants who received at least one dose of study treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Pembrolizumab (MK-3475) Versus Investigator's Choice of Chemotherapy for Participants With Advanced Esophageal/Esophagogastric Junction Carcinoma That Progressed After First-Line Therapy (MK-3475-181/KEYNOTE-181)-China Extension Study	NCT03933449	Esophageal Carc... Esophagogastric...	pembrolizumab paclitaxel docetaxel irinotecan	18 Years -	Merck Sharp & Dohme LLC
Study of Pembrolizumab (MK-3475) Versus Investigator's Choice of Chemotherapy for Participants With Advanced Esophageal/Esophagogastric Junction Carcinoma That Progressed After First-Line Therapy (MK-3475-181/KEYNOTE-181)-China Extension Study	NCT03933449	Esophageal Carc... Esophagogastric...	pembrolizumab paclitaxel docetaxel irinotecan	18 Years -	Merck Sharp & Dohme LLC

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