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

Phase 3

Completed

• Conditions: Esophageal Neoplasms
• Interventions: Biological: Pembrolizumab; Drug: Placebo; Drug: Cisplatin; Drug: 5-FU

• Registration Number: NCT03189719
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2017-06-14
• Study First Submitted QC: 2017-06-15
• Study First Posted: 2017-06-16
• Study Start: 2017-07-25
• Primary Completion: 2020-07-02
• Results First Submitted: 2021-05-18
• Results First Submitted QC: 2021-06-14
• Results First Posted: 2021-07-06
• Study Completion: 2023-07-10
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-10
• Last Update Posted: 2024-10-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 749

Inclusion Criteria

• Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the esophagogastric junction (EGJ)
• Has measurable disease per RECIST 1.1 as determined by the local site investigator/radiology assessment
• Eastern Cooperative Group (ECOG) performance status of 0 to 1
• Can provide either a newly obtained or archival tissue sample for PD-L1 by immunohistochemistry analysis
• Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to randomization and be willing to use an adequate method of contraception (e.g. abstinence, intrauterine device, diaphragm with spermicide, etc.) for the course of the study through 120 days after the last dose of study treatment and up to 180 days after last dose of cisplatin
• Male participants of childbearing potential must agree to use an adequate method of contraception (e.g. abstinence, vasectomy, male condom, etc.) starting with the first dose of study treatment through 120 days after the last dose of study treatment and up to 180 days after last dose of cisplatin, and refrain from donating sperm during this period
• Has adequate organ function

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Exclusion Criteria

• Has locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy (as determined by local investigator)
• Has had previous therapy for advanced/metastatic adenocarcinoma or squamous cell cancer of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the EGJ
• Has had major surgery, open biopsy, or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study treatment
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ breast cancer that has undergone potentially curative therapy, and in situ or intramucosal pharyngeal cancer
• Has known active central nervous system metastases and/or carcinomatous meningitis.
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment, or has a history of organ transplant, including allogeneic stem cell transplant
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis, or has an active infection requiring systemic therapy
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study medication and up to 180 days after last dose of cisplatin
• Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in a pembrolizumab (MK-3475) clinical trial
• Has severe hypersensitivity (≥ Grade 3) to any study treatment (pembrolizumab, cisplatin, or 5-FU) and/or any of its excipients
• Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis) or human immunodeficiency virus (HIV) infection
• Has known history of or is positive for hepatitis B or hepatitis C
• Has received a live vaccine within 30 days prior to the first dose of study treatment
• Has had radiotherapy within 14 days of randomization. Participants who received radiotherapy >14 days prior to randomization must have completely recovered from any radiotherapy-related AEs/toxicities

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pembrolizumab + SOC	Pembrolizumab	Participants receive pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) plus standard of care (SOC) chemotherapy with cisplatin 80 mg/m\^2 IV Q3W and 5-FU 800 mg/m\^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments will be administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Pembrolizumab + SOC	5-FU	Participants receive pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) plus standard of care (SOC) chemotherapy with cisplatin 80 mg/m\^2 IV Q3W and 5-FU 800 mg/m\^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments will be administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Placebo + SOC	Placebo	Participants receive placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m\^2 IV Q3W and 5-FU 800 mg/m\^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments will be administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Pembrolizumab + SOC	Cisplatin	Participants receive pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) plus standard of care (SOC) chemotherapy with cisplatin 80 mg/m\^2 IV Q3W and 5-FU 800 mg/m\^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments will be administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Placebo + SOC	5-FU	Participants receive placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m\^2 IV Q3W and 5-FU 800 mg/m\^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments will be administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Placebo + SOC	Cisplatin	Participants receive placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m\^2 IV Q3W and 5-FU 800 mg/m\^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments will be administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.

Primary Outcome Measures

Name	Time	Method
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)	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.
OS in Participants With ESCC	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.
OS in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	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.
OS in All Participants	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).
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	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 participants of the ITT population (all randomized) who had ESCC.
PFS Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	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 participants of the ITT population (all randomized) who were PD-L1 CPS ≥10.
PFS Per RECIST 1.1 As Assessed By Investigator in All Participants	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 participants of the ITT population (all randomized).

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) Per RECIST 1.1 As Assessed By Investigator in All Participants	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).
ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	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.
ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC	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.
ORR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	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.
Duration of Response (DOR) Per RECIST 1.1 As Assessed By Investigator in All Participants	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 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. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR.
DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	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 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. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR, and who had ESCC and were PD-L1 CPS ≥10.
DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC	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 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. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR, and who had ESCC.
DOR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	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 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. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR, and were PD-L1 CPS ≥10.
Number of Participants With an Adverse Event (AE)	Up to approximately 28 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 AE. The number of participants that experienced at least one AE was reported for each treatment arm.
Number of Participants Discontinuing Study Treatment Due to an AE	Up to approximately 27 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 AE. The number of participants that discontinued any study drug due to an AE was reported for each treatment arm.
Change From Baseline To Week 18 in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Combined Score in All Participants	Baseline, Week 18	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants.
Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	Baseline, Week 18	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants who had ESCC and who were PD-L1 CPS ≥10.
Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants With ESCC	Baseline, Week 18	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants who had ESCC.
Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	Baseline, Week 18	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants who were PD-L1 CPS ≥10.
Change From Baseline in the EORTC Quality Of Life Questionnaire Oesophageal Module (QLQ-OES18) Subscale Scores in All Participants	Baseline, Week 18	The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores represent a higher ("worse") level of symptoms. Per protocol, change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for all participants in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity.
Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	Baseline, Week 18	The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores representing a higher ("worse") level of symptoms. Change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for participants with ESCC who were PD-L1 CPS≥10 in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity.
Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC	Baseline, Week 18	The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores representing a higher ("worse") level of symptoms. Change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for participants with ESCC in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity.
Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	Baseline, Week 18	The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores representing a higher ("worse") level of symptoms. Change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for participants who were PD-L1 CPS≥10 in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity.

Trial Locations

Locations (189)

The Medical Oncology Centre of Rosebank ( Site 2506); 🇿🇦 Johannesburg, Gauteng, South Africa

Hospital Universitario Central de Asturias ( Site 0708); 🇪🇸 Oviedo, Asturias, Spain

University of Maryland Medical Center ( Site 0013); 🇺🇸 Baltimore, Maryland, United States

The University of Chicago Medical Center ( Site 0001); 🇺🇸 Chicago, Illinois, United States

Phramongkutklao Hospital ( Site 2205); 🇹🇭 Bangkok, Thailand

Clinica Alemana de Temuco ( Site 1006); 🇨🇱 Temuco, Chile

CIMCA Centro de Investigacion y Manejo del Cancer ( Site 2600); 🇨🇷 San Jose, Costa Rica

Inst de Medicina Integral Professor Fernando Figueira- IMIP ( Site 0210); 🇧🇷 Recife, Pernambuco, Brazil

University Malaya Medical Centre ( Site 1802); 🇲🇾 Kuala Lumpur, Malaysia

S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 2404); 🇷🇴 Craiova, Dolj, Romania

Chang Gung Med Foundation. Kaohsiung Branch ( Site 1906); 🇨🇳 Kaohsiung, Taiwan

Hospital Regional de Concepcion Dr. Guillermo Grant Benavente ( Site 1003); 🇨🇱 Concepcion, Chile

Hospital Clinico Universidad de Chile ( Site 1002); 🇨🇱 Santiago, Chile

Beacon International Specialist Centre ( Site 1803); 🇲🇾 Petaling Jaya, Selangor, Malaysia

Rodrigo Botero SAS ( Site 2703); 🇨🇴 Medellin, Antioquia, Colombia

Oncomedica S.A. ( Site 2701); 🇨🇴 Monteria, Cordoba, Colombia

Policlinico San Bosco ( Site 2602); 🇨🇷 San Jose, Costa Rica

Hospital Nacional Guillermo Almenara Irigoyen ( Site 1701); 🇵🇪 Lima, Peru

Chulalongkorn Hospital ( Site 2201); 🇹🇭 Bangkok, Thailand

Pamela Youde Nethersole Eastern Hospital ( Site 1601); 🇭🇰 Hong Kong, Hong Kong

Spitalul Clinic Judetean De Urgenta Constanta ( Site 2402); 🇷🇴 Constanta, Romania

Hospital Kuala Lumpur ( Site 1805); 🇲🇾 Kuala Lumpur, Malaysia

S C Pelican Impex SRL ( Site 2403); 🇷🇴 Oradea, Bihor, Romania

Instituto Regional de Enfermedades Neoplasicas del Sur IRENSUR ( Site 1702); 🇵🇪 Arequipa, Peru

S.C. Radiotherapy Center Cluj S.R.L ( Site 2407); 🇷🇴 Comuna Floresti, Cluj, Romania

S C Oncocenter Oncologie Medicala S R L ( Site 2405); 🇷🇴 Timisoara, Timis, Romania

S.C.Gral Medical S.R.L ( Site 2406); 🇷🇴 Bucuresti, Romania

Ramathibodi Hospital. ( Site 2202); 🇹🇭 Bangkok, Thailand

Outeniqua Cancercare Oncology Unit ( Site 2504); 🇿🇦 George, Western Cape, South Africa

Instituto Nacional de Enfermedades Neoplasicas ( Site 1705); 🇵🇪 Lima, Peru

China Medical University Hospital ( Site 1904); 🇨🇳 Taichung, Taiwan

Kuang Tien General Hospital ( Site 1909); 🇨🇳 Taichung, Taiwan

Cancer Care Langenhoven Drive Oncology Centre ( Site 2501); 🇿🇦 Port Elizabeth, Eastern Cape, South Africa

National Taiwan University Hospital ( Site 1900); 🇨🇳 Taipei, Taiwan

The First Affiliated Hospital of Anhui Medical University ( Site 0112); 🇨🇳 Hefei, Anhui, China

Guangdong General Hospital ( Site 0103); 🇨🇳 Guangzhou, Guangdong, China

Tongji Medical College Huazhong University of Science and Technology ( Site 0109); 🇨🇳 Wuhan, Hubei, China

The Affiliated Tumour Hospital of Harbin Medical University ( Site 0102); 🇨🇳 Harbin, Heilongjiang, China

Zhejiang Cancer Hospital ( Site 0116); 🇨🇳 Hangzhou, Zhejiang, China

Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0114); 🇨🇳 Shanghai, China

Fujian Provincial Cancer Hospital ( Site 0104); 🇨🇳 Fuzhou, China

Shanghai Chest Hospital ( Site 0111); 🇨🇳 Shanghai, China

Dana Farber Cancer Center ( Site 0009); 🇺🇸 Boston, Massachusetts, United States

Henry Ford Cancer Center ( Site 0018); 🇺🇸 Detroit, Michigan, United States

UPMC Cancer Center/Hillman Cancer Center ( Site 0015); 🇺🇸 Pittsburgh, Pennsylvania, United States

University Hospitals Cleveland Medical Center ( Site 0002); 🇺🇸 Cleveland, Ohio, United States

Washington University School of Medicine ( Site 0031); 🇺🇸 Saint Louis, Missouri, United States

Instituto do Cancer de Sao Paulo - ICESP ( Site 0206); 🇧🇷 Sao Paulo, Brazil

Hospital Aleman ( Site 0605); 🇦🇷 Buenos Aires, Argentina

Hospital Privado Centro Medico Cordoba ( Site 0601); 🇦🇷 Cordoba, Argentina

The Ottawa Hospital - Cancer Care ( Site 0501); 🇨🇦 Ottawa, Ontario, Canada

Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0209); 🇧🇷 Rio de Janeiro, RJ, Brazil

Peking Union Medical College Hospital ( Site 0123); 🇨🇳 Beijing, Beijing, China

University of Tennessee Medical Center Knoxville ( Site 0017); 🇺🇸 Knoxville, Tennessee, United States

Princess Margaret Cancer Centre ( Site 0505); 🇨🇦 Toronto, Ontario, Canada

CancerCare Manitoba ( Site 0500); 🇨🇦 Winnipeg, Manitoba, Canada

Sanatorio Allende - Cordoba ( Site 0604); 🇦🇷 Cordoba, Argentina

Hospital de Clinicas de Porto Alegre ( Site 0200); 🇧🇷 Porto Alegre, Brazil

ICIMED - Instituto de Investigacion en Ciencias Medicas ( Site 2601); 🇨🇷 San Jose, Costa Rica

The First Affiliated Hospital of Xiamen University ( Site 0119); 🇨🇳 Xiamen, Fujian, China

Hunan Cancer Hospital ( Site 0105); 🇨🇳 Changsha, Hunan, China

Jilin Cancer Hospital ( Site 0101); 🇨🇳 Changchun, Jilin, China

Hospital Alemao Oswaldo Cruz ( Site 0207); 🇧🇷 Sao Paulo, SP, Brazil

Clinica de Hematologia e Oncologia Viver Ltda ( Site 0211); 🇧🇷 Santa Maria, Rio Grande Do Sul, Brazil

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto. ( Site 0203); 🇧🇷 Sao Jose do Rio Preto, Sao Paulo, Brazil

CHU de Nantes - Hotel Dieu ( Site 0303); 🇫🇷 Nantes Cedex 1, France

Hospital Sao Vicente de Paulo ( Site 0204); 🇧🇷 Passo Fundo, RS, Brazil

Universitaetsklinikum Leipzig ( Site 1501); 🇩🇪 Leipzig, Germany

Klinikum Ludwigsburg ( Site 1509); 🇩🇪 Ludwigsburg, Germany

Kyushu University Hospital ( Site 0922); 🇯🇵 Fukuoka, Japan

Hyogo Cancer Center ( Site 0913); 🇯🇵 Akashi, Hyogo, Japan

Klinik fuer Haematologie. Onkologie und Gastroenterologie ( Site 1508); 🇩🇪 Moenchengladbach, Germany

Seoul National University Cancer Hospital ( Site 1301); 🇰🇷 Seoul, Korea, Republic of

Koo Foundation Sun Yat-Sen Cancer Center ( Site 1902); 🇨🇳 Taipei, Taiwan

Adana Sehir Hastanesi ( Site 0802); 🇹🇷 Adana, Turkey

Centre Francois Baclesse ( Site 0310); 🇫🇷 Caen, France

National Hospital Organization Shikoku Cancer Center ( Site 0901); 🇯🇵 Matsuyama, Ehime, Japan

Saitama Cancer Center ( Site 0926); 🇯🇵 Kitaadachi-gun, Saitama, Japan

The Oncology Centre ( Site 2502); 🇿🇦 Durban, Kwa-Zulu Natal, South Africa

Kaiser Permanente Southern California ( Site 0003); 🇺🇸 West Los Angeles, California, United States

University of Kansas ( Site 0029); 🇺🇸 Westwood, Kansas, United States

Weill Cornell Medical College ( Site 0024); 🇺🇸 New York, New York, United States

Hospital Municipal de Gastroenterologia Dr. Bonorino Udaondo ( Site 0602); 🇦🇷 Buenos Aires, Argentina

Centro de Investigaciones Clinicas - Clinica Viedma ( Site 0603); 🇦🇷 Viedma, Rio Negro, Argentina

Liverpool Hospital. ( Site 2001); 🇦🇺 Liverpool, New South Wales, Australia

Blacktown Hospital ( Site 2000); 🇦🇺 Blacktown, New South Wales, Australia

Princess Alexandra Hospital ( Site 2005); 🇦🇺 Woolloongabba, Queensland, Australia

Henan Cancer Hospital ( Site 0107); 🇨🇳 Zhengzhou, China

CISSS de la Monteregie-Centre ( Site 0504); 🇨🇦 Greenfield Park, Quebec, Canada

Anhui Provincial Hospital ( Site 0106); 🇨🇳 Hefei, Anhui, China

Pontificia Universidad Catolica de Chile ( Site 1001); 🇨🇱 Santiago, Chile

Jewish General Hospital ( Site 0507); 🇨🇦 Montreal, Quebec, Canada

The First Affiliated Hospital of Xi an Jiaotong University ( Site 0120); 🇨🇳 Xi'an, Shannxi, China

Fudan University Shanghai Cancer Center ( Site 0108); 🇨🇳 Shanghai, China

Odense Universitetshospital ( Site 2300); 🇩🇰 Odense, Denmark

Centre Leon Berard ( Site 0307); 🇫🇷 Lyon, Cedex 8, France

Institut du Cancer de Montpellier ( Site 0306); 🇫🇷 Montpellier, France

Centre Oscar Lambret ( Site 0304); 🇫🇷 Lille, France

CHU Brest - Institut de Cancerologie et d Hematologie ( Site 0305); 🇫🇷 Brest, France

Institut Mutualiste Montsouris ( Site 0300); 🇫🇷 Paris, France

CHU de Saint Etienne Hopital Nord ( Site 0309); 🇫🇷 Saint Etienne, France

Staedtisches Klinikum Dresden ( Site 1507); 🇩🇪 Dresden, Germany

Haematologisch-Onkologische Praxis Eppendorf Facharztzentrum Eppendorf - Hope ( Site 1502); 🇩🇪 Hamburg, Germany

Universitatsklinikum Mannheim GmbH ( Site 1504); 🇩🇪 Mannheim, Germany

Oncomedica ( Site 1400); 🇬🇹 Guatemala, Guatemala

Medi-K Cayala ( Site 1404); 🇬🇹 Guatemala, Guatemala

III. Medizinische Klinik Klinikum rechts der Isar ( Site 1506); 🇩🇪 Munchen, Germany

Centro de Investigacion Oncologica ( Site 1402); 🇬🇹 Guatemala, Guatemala

Grupo Medico Angeles ( Site 1401); 🇬🇹 Guatemala, Guatemala

Centro Regional de Sub Especialidades Medicas SA ( Site 1403); 🇬🇹 Quetzaltenango, Guatemala

Hokkaido University Hospital ( Site 0916); 🇯🇵 Sapporo, Hokkaido, Japan

Aichi Cancer Center Hospital ( Site 0902); 🇯🇵 Nagoya, Aichi, Japan

National Cancer Center Hospital East ( Site 0908); 🇯🇵 Kashiwa, Chiba, Japan

Kobe City Medical Center General Hospital ( Site 0929); 🇯🇵 Kobe, Hyogo, Japan

Ibaraki Prefectural Central Hospital ( Site 0918); 🇯🇵 Kasama, Ibaraki, Japan

University of Tsukuba Hospital ( Site 0910); 🇯🇵 Tsukuba, Ibaraki, Japan

St. Marianna University School of Medicine Hospital ( Site 0903); 🇯🇵 Kawasaki, Kanagawa, Japan

Kagawa University Hospital ( Site 0915); 🇯🇵 Kita-gun, Kagawa, Japan

Kanagawa Cancer Center ( Site 0921); 🇯🇵 Yokohama, Kanagawa, Japan

Oita University Hospital ( Site 0930); 🇯🇵 Yufu, Oita, Japan

Osaka University Hospital ( Site 0911); 🇯🇵 Suita, Osaka, Japan

Kindai University Hospital ( Site 0917); 🇯🇵 Osakasayama, Osaka, Japan

Osaka Medical College Hospital ( Site 0925); 🇯🇵 Takatsuki, Osaka, Japan

Shizuoka Cancer Center Hospital and Research Institute ( Site 0914); 🇯🇵 Sunto-gun, Shizuoka, Japan

Gifu University Hospital ( Site 0920); 🇯🇵 Gifu, Japan

Kyorin University Hospital ( Site 0905); 🇯🇵 Mitaka, Tokyo, Japan

National Hospital Organization Kyushu Cancer Center ( Site 0906); 🇯🇵 Fukuoka, Japan

Chiba University Hospital ( Site 0909); 🇯🇵 Chiba, Japan

Chiba Cancer Center ( Site 0900); 🇯🇵 Chiba, Japan

Kumamoto University Hospital ( Site 0919); 🇯🇵 Kumamoto, Japan

National Cancer Center Hospital ( Site 0907); 🇯🇵 Tokyo, Japan

Niigata Cancer Center Hospital ( Site 0924); 🇯🇵 Niigata, Japan

Osaka General Medical Center ( Site 0912); 🇯🇵 Osaka, Japan

Osaka International Cancer Institute ( Site 0923); 🇯🇵 Osaka, Japan

The Cancer Institute Hospital of JFCR ( Site 0904); 🇯🇵 Tokyo, Japan

Keio University Hospital ( Site 0927); 🇯🇵 Tokyo, Japan

Chonnam National University Hwasun Hospital ( Site 1305); 🇰🇷 Hwasun Gun, Jeollanam Do, Korea, Republic of

Samsung Medical Center ( Site 1300); 🇰🇷 Seoul, Korea, Republic of

Severance Hospital Yonsei University Health System ( Site 1302); 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center ( Site 1303); 🇰🇷 Seoul, Korea, Republic of

S.C.Focus Lab Plus S.R.L ( Site 2401); 🇷🇴 Bucuresti, Sector 2, Romania

SBHCI RCOD of MHC RB ( Site 0407); 🇷🇺 Ufa, Republic Of Bashkortostan, Russian Federation

Leningrad Regional Oncology Center ( Site 0405); 🇷🇺 Saint-Petersburg, Vsevolzhsk District, Russian Federation

National Medical and Surgical Center n.a. N.I.Pirogov ( Site 0402); 🇷🇺 Moscow, Russian Federation

N.N. Blokhin NMRCO ( Site 0401); 🇷🇺 Moscow, Russian Federation

Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 0406); 🇷🇺 Saint-Petersburg, Russian Federation

Tomsk Scientific Research Institute of Oncology ( Site 0403); 🇷🇺 Tomsk, Russian Federation

WITS Clinical Research CMJAH Clinical Trial Site ( Site 2500); 🇿🇦 Parktown, Gauteng, South Africa

St Petersburg City Clinical Oncology Dispensary ( Site 0409); 🇷🇺 St. Petersburg, Russian Federation

Cape Town Oncology Trials Pty Ltd ( Site 2508); 🇿🇦 Cape Town, Western Cape, South Africa

Hosp. Gral. Universitari Germans Trias i Pujol ( Site 0701); 🇪🇸 Badalona, Barcelona, Spain

Clinton Oncology Centre ( Site 2505); 🇿🇦 Alberton, South Africa

Hospital Universitario Reina Sofia ( Site 0706); 🇪🇸 Cordoba, Spain

Hospital Universitari Vall d Hebron ( Site 0702); 🇪🇸 Barcelona, Spain

Hospital Ramon y Cajal ( Site 0703); 🇪🇸 Madrid, Spain

Complejo Hospitalario Virgen De La Victoria ( Site 0705); 🇪🇸 Malaga, Spain

Taipei Medical University Shuang Ho Hospital ( Site 1908); 🇨🇳 New Taipei, Taiwan

Hospital Universitario La Paz ( Site 0700); 🇪🇸 Madrid, Spain

National Cheng Kung University Hospital ( Site 1905); 🇨🇳 Tainan, Taiwan

Chi Mei Medical Center Liuying ( Site 1907); 🇨🇳 Tainan, Taiwan

Bumrungrad International Hospital ( Site 2203); 🇹🇭 Bangkok, Thailand

Chang Gung Medical Foundation. Linkou ( Site 1903); 🇨🇳 Taoyuan, Taiwan

Songklanagarind Hospital ( Site 2204); 🇹🇭 Songkla, Thailand

Ankara Sehir Hastanesi ( Site 0808); 🇹🇷 Ankara, Turkey

Istanbul Medeniyet Universitesi Goztepe EAH ( Site 0807); 🇹🇷 Istanbul, Turkey

Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0804); 🇹🇷 Istanbul, Turkey

Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 0801); 🇹🇷 Istanbul, Turkey

Medical Park Izmir Hastanesi ( Site 0800); 🇹🇷 Izmir, Turkey

Inonu Universitesi Turgut Ozal Tip Merkezi ( Site 0803); 🇹🇷 Malatya, Turkey

The Christie NHS Foundation Trust ( Site 1100); 🇬🇧 Manchester, United Kingdom

Lothian University Hospitals NHS Trust ( Site 1101); 🇬🇧 Edinburgh, Mid Lothian, United Kingdom

St Luke's Cancer Centre ( Site 1102); 🇬🇧 Guildford, United Kingdom

Eastern Health ( Site 2002); 🇦🇺 Box Hill, Victoria, Australia

Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0201); 🇧🇷 Porto Alegre, RS, Brazil

Kansai Medical University Hospital ( Site 0931); 🇯🇵 Hirakata, Osaka, Japan

National Cancer Center ( Site 1304); 🇰🇷 Goyang-si, Gyeonggi-do, Korea, Republic of

Roswell Park Cancer Institute ( Site 0004); 🇺🇸 Buffalo, New York, United States

Peter MacCallum Cancer Centre ( Site 2003); 🇦🇺 Melbourne, Victoria, Australia

CETUS Hospital Dia Oncologia ( Site 0208); 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

Tom Baker Cancer Centre ( Site 0503); 🇨🇦 Calgary, Alberta, Canada

Cross Cancer Institute ( Site 0502); 🇨🇦 Edmonton, Alberta, Canada

Juravinski Cancer Center ( Site 0508); 🇨🇦 Hamilton, Ontario, Canada

Beijing Cancer Hospital ( Site 0100); 🇨🇳 Beijing, China

PLA Cancer Centre of Nanjing Bayi Hospital ( Site 0110); 🇨🇳 Nanjing, Jiangsu, China

Zhongda Hospital Southeast University ( Site 0125); 🇨🇳 Nanjing, Jiangsu, China

Rigshospitalet ( Site 2301); 🇩🇰 Copenhagen, Denmark

Humanity Health Research Centre ( Site 1603); 🇭🇰 Hong Kong, Hong Kong

Princess Margaret Hospital. ( Site 1602); 🇭🇰 Hong Kong, Hong Kong

Queen Mary Hospital ( Site 1600); 🇭🇰 Hong Kong, Hong Kong