Esophageal Neoplasms
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1),, Programmed Cell Death Receptor Ligand 1 (PDL1, PD-L1), Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2)
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.
Interventions
BIOLOGICALPembrolizumab
200 mg administered IV Q3W on Day 1 of each 3-week cycle, up to 35 administrations.
DRUGPlacebo
Placebo to pembrolizumab (saline) administered IV Q3W on Day 1 of each 3-week cycle, up to 35 administrations.
DRUGCisplatin
80 mg/m\^2 administered IV Q3W on Day 1 of each 3-week cycle. Duration of cisplatin treatment will be capped at 6 doses.
DRUG5-FU
800 mg/m\^2/day (4000 mg/m\^2 total per cycle) administered as continuous IV infusion on Days 1 to 5 (120 hours) of each 3-week cycle, or per local standard for 5-FU administration, up to 35 administrations.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
Countries
Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Costa Rica, Denmark, France, Germany, Guatemala, Hong Kong, Japan, Malaysia, Peru, Romania, Russia, South Africa, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
749 participants were randomized 1:1 to receive either pembrolizumab plus standard of care (SOC) chemotherapy, or placebo plus SOC chemotherapy.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab + SOC Participants received pembrolizumab 200 mg 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 were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle. | 373 |
| Placebo + SOC Participants received 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 were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle. | 376 |
| Total | 749 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 325 | 361 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Sponsor Decision | 40 | 12 |
| Overall Study | Withdrawal by Subject | 7 | 3 |
Baseline characteristics
| Characteristic | Pembrolizumab + SOC | Total | Placebo + SOC |
|---|---|---|---|
| Age, Continuous | 62.8 Years STANDARD_DEVIATION 9.8 | 62.4 Years STANDARD_DEVIATION 9.5 | 62.0 Years STANDARD_DEVIATION 9.2 |
| Eastern Cooperative Group Performance Status (ECOG PS) ECOG PS 0 | 149 Participants | 299 Participants | 150 Participants |
| Eastern Cooperative Group Performance Status (ECOG PS) ECOG PS 1 | 223 Participants | 448 Participants | 225 Participants |
| Eastern Cooperative Group Performance Status (ECOG PS) ECOG PS 2 | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 42 Participants | 99 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 315 Participants | 611 Participants | 296 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 16 Participants | 39 Participants | 23 Participants |
| Geographic Region Asia | 196 Participants | 393 Participants | 197 Participants |
| Geographic Region Rest of World | 177 Participants | 356 Participants | 179 Participants |
| Histology Adenocarcinoma | 99 Participants | 201 Participants | 102 Participants |
| Histology Squamous Cell Carcinoma | 274 Participants | 548 Participants | 274 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 9 Participants | 21 Participants | 12 Participants |
| Race (NIH/OMB) Asian | 201 Participants | 400 Participants | 199 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 7 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 14 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 14 Participants | 29 Participants | 15 Participants |
| Race (NIH/OMB) White | 139 Participants | 278 Participants | 139 Participants |
| Sex: Female, Male Female | 67 Participants | 124 Participants | 57 Participants |
| Sex: Female, Male Male | 306 Participants | 625 Participants | 319 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 331 / 373 | 363 / 376 |
| other Total, other adverse events | 367 / 370 | 364 / 370 |
| serious Total, serious adverse events | 207 / 370 | 204 / 370 |
Outcome results
Primary
OS in All Participants
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).
Time frame: Up to approximately 34 months
Population: All randomized participants (ITT population) were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + SOC | OS in All Participants | 12.4 Months |
| Placebo + SOC | OS in All Participants | 9.8 Months |
Comparison: OS in all participants of the pembrolizumab + SOC arm was compared to OS in all participants of the placebo + SOC arm based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by geographic region (Asia versus Rest of the World), tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma), and ECOG performance status (0 versus 1).p-value: <0.000195% CI: [0.62, 0.86]Stratified Log-Rank
Primary
OS in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
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.
Time frame: Up to approximately 34 months
Population: All randomized participants (ITT population) who were PD-L1 CPS ≥10 were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + SOC | OS in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | 13.5 Months |
| Placebo + SOC | OS in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | 9.4 Months |
Comparison: OS in PD-L1 CPS ≥10 participants of the pembrolizumab + SOC arm was compared to OS in PD-L1 CPS ≥10 participants of the placebo + SOC arm based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma).p-value: <0.000195% CI: [0.49, 0.78]Stratified Log-Rank
Primary
OS in Participants With ESCC
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.
Time frame: Up to approximately 34 months
Population: All randomized participants (ITT population) with ESCC were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + SOC | OS in Participants With ESCC | 12.6 Months |
| Placebo + SOC | OS in Participants With ESCC | 9.8 Months |
Comparison: OS in ESCC participants of the pembrolizumab + SOC arm was compared to OS in ESCC participants of the placebo + SOC arm based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).p-value: 0.000695% CI: [0.6, 0.88]Stratified Log-Rank
Primary
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)
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.
Time frame: Up to approximately 34 months
Population: All randomized participants (ITT population) with ESCC and PD-L1 CPS ≥10 were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + SOC | 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) | 13.9 Months |
| Placebo + SOC | 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) | 8.8 Months |
Comparison: OS in ESCC PD-L1 CPS ≥10 participants of the pembrolizumab + SOC arm was compared to OS in ESCC PD-L1 CPS ≥10 participants of the placebo + SOC arm based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).p-value: <0.000195% CI: [0.43, 0.75]Stratified Log-Rank
Primary
PFS Per RECIST 1.1 As Assessed By Investigator in All Participants
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).
Time frame: Up to approximately 34 months
Population: All randomized participants (ITT population) were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + SOC | PFS Per RECIST 1.1 As Assessed By Investigator in All Participants | 6.3 Months |
| Placebo + SOC | PFS Per RECIST 1.1 As Assessed By Investigator in All Participants | 5.8 Months |
Comparison: PFS in all participants of the pembrolizumab + SOC arm was compared to PFS in all participants of the placebo + SOC arm based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by geographic region (Asia versus Rest of the World), tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma), and ECOG performance status (0 versus 1).p-value: <0.000195% CI: [0.55, 0.76]Stratified Log-Rank
Primary
PFS Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
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.
Time frame: Up to approximately 34 months
Population: All randomized participants (ITT population) who were PD-L1 CPS ≥10 were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + SOC | PFS Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | 7.5 Months |
| Placebo + SOC | PFS Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | 5.5 Months |
Comparison: PFS in PD-L1 CPS ≥10 participants of the pembrolizumab + SOC arm was compared to PFS in PD-L1 CPS ≥10 participants of the placebo + SOC arm based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma).p-value: <0.000195% CI: [0.41, 0.65]Stratified Log-Rank
Primary
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
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.
Time frame: Up to approximately 34 months
Population: All randomized participants (ITT population) with ESCC were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + SOC | 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 | 6.3 Months |
| Placebo + SOC | 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 | 5.8 Months |
Comparison: PFS in ESCC participants of the pembrolizumab + SOC arm was compared to PFS in ESCC participants of the placebo + SOC arm based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).p-value: <0.000195% CI: [0.54, 0.78]Stratified Log-Rank
Secondary
Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
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.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study treatment, completed at least 1 EORTC QLQ-OES18 assessment, and with PD-L1 CPS ≥10 were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Pembrolizumab + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | Dysphagia subscale | -7.18 Score on a Scale |
| Pembrolizumab + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | Pain subscale | -3.51 Score on a Scale |
| Pembrolizumab + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | Reflux subscale | -0.52 Score on a Scale |
| Placebo + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | Dysphagia subscale | 1.02 Score on a Scale |
| Placebo + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | Pain subscale | 0.07 Score on a Scale |
| Placebo + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | Reflux subscale | 4.25 Score on a Scale |
Comparison: DYSPHAGIA: Change from baseline to Week 18 in EORTC QLQ-OES18 Dysphagia subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma).p-value: 0.031795% CI: [-15.67, -0.73]constrained Longitudinal Data Analysis
Comparison: PAIN: Change from baseline to Week 18 in EORTC QLQ-OES18 Pain subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma).p-value: 0.094595% CI: [-7.77, 0.62]constrained Longitudinal Data Analysis
Comparison: REFLUX: Change from baseline to Week 18 in EORTC QLQ-OES18 Reflux subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma).p-value: 0.055595% CI: [-9.64, 0.11]constrained Longitudinal Data Analysis
Secondary
Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC
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.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study treatment, completed at least 1 EORTC QLQ-OES18 assessment, and with ESCC were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Pembrolizumab + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC | Dysphagia subscale | -1.18 Score on a Scale |
| Pembrolizumab + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC | Pain subscale | -4.03 Score on a Scale |
| Pembrolizumab + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC | Reflux subscale | -0.40 Score on a Scale |
| Placebo + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC | Dysphagia subscale | 3.32 Score on a Scale |
| Placebo + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC | Pain subscale | -2.33 Score on a Scale |
| Placebo + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC | Reflux subscale | 1.09 Score on a Scale |
Comparison: DYSPHAGIA: Change from baseline to Week 18 in EORTC QLQ-OES18 Dysphagia subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).p-value: 0.163295% CI: [-10.81, 1.83]constrained Longitudinal Data Analysis
Comparison: PAIN: Change from baseline to Week 18 in EORTC QLQ-OES18 Pain subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).p-value: 0.325995% CI: [-5.12, 1.71]constrained Longitudinal Data Analysis
Comparison: REFLUX: Change from baseline to Week 18 in EORTC QLQ-OES18 Reflux subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).p-value: 0.459895% CI: [-5.47, 2.48]constrained Longitudinal Data Analysis
Secondary
Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
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.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study treatment, completed at least 1 EORTC QLQ-OES18 assessment, and with ESCC and PD-L1 CPS ≥10 were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Pembrolizumab + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | Dysphagia subscale | -5.11 Score on a Scale |
| Pembrolizumab + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | Pain subscale | -2.55 Score on a Scale |
| Pembrolizumab + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | Reflux subscale | -0.16 Score on a Scale |
| Placebo + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | Dysphagia subscale | 3.57 Score on a Scale |
| Placebo + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | Pain subscale | -0.42 Score on a Scale |
| Placebo + SOC | Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | Reflux subscale | 4.94 Score on a Scale |
Comparison: DYSPHAGIA: Change from baseline to Week 18 in EORTC QLQ-OES18 Dysphagia subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).p-value: 0.056495% CI: [-17.59, 0.24]constrained Longitudinal Data Analysis
Comparison: PAIN: Change from baseline to Week 18 in EORTC QLQ-OES18 Pain subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).p-value: 0.381395% CI: [-6.93, 2.66]constrained Longitudinal Data Analysis
Comparison: REFLUX: Change from baseline to Week 18 in EORTC QLQ-OES18 Reflux subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).p-value: 0.081695% CI: [-10.86, 0.65]constrained Longitudinal Data Analysis
Secondary
Change From Baseline in the EORTC Quality Of Life Questionnaire Oesophageal Module (QLQ-OES18) Subscale Scores in All Participants
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.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study treatment and completed at least 1 EORTC QLQ-OES18 assessment were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Pembrolizumab + SOC | Change From Baseline in the EORTC Quality Of Life Questionnaire Oesophageal Module (QLQ-OES18) Subscale Scores in All Participants | Dysphagia subscale | -3.18 Score on a Scale |
| Pembrolizumab + SOC | Change From Baseline in the EORTC Quality Of Life Questionnaire Oesophageal Module (QLQ-OES18) Subscale Scores in All Participants | Pain subscale | -4.78 Score on a Scale |
| Pembrolizumab + SOC | Change From Baseline in the EORTC Quality Of Life Questionnaire Oesophageal Module (QLQ-OES18) Subscale Scores in All Participants | Reflux subscale | -0.22 Score on a Scale |
| Placebo + SOC | Change From Baseline in the EORTC Quality Of Life Questionnaire Oesophageal Module (QLQ-OES18) Subscale Scores in All Participants | Dysphagia subscale | 2.36 Score on a Scale |
| Placebo + SOC | Change From Baseline in the EORTC Quality Of Life Questionnaire Oesophageal Module (QLQ-OES18) Subscale Scores in All Participants | Pain subscale | -1.85 Score on a Scale |
| Placebo + SOC | Change From Baseline in the EORTC Quality Of Life Questionnaire Oesophageal Module (QLQ-OES18) Subscale Scores in All Participants | Reflux subscale | 0.71 Score on a Scale |
Comparison: DYSPHAGIA: Change from baseline to Week 18 in EORTC QLQ-OES18 Dysphagia subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma) and ECOG performance status (0 versus 1).p-value: 0.043695% CI: [-10.93, -0.16]constrained Longitudinal Data Analysis
Comparison: PAIN: Change from baseline to Week 18 in EORTC QLQ-OES18 Pain subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma) and ECOG performance status (0 versus 1).p-value: 0.048795% CI: [-5.86, -0.02]constrained Longitudinal Data Analysis
Comparison: REFLUX: Change from baseline to Week 18 in EORTC QLQ-OES18 Reflux subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma) and ECOG performance status (0 versus 1).p-value: 0.593295% CI: [-4.36, 2.49]constrained Longitudinal Data Analysis
Secondary
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)
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.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study treatment, completed at least 1 EORTC-QLQ-C30 assessment, and who were PD-L1 CPS ≥10 were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembrolizumab + SOC | 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) | -1.73 Score on a Scale |
| Placebo + SOC | 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) | 0.04 Score on a Scale |
Comparison: Change from baseline to Week 18 in EORTC-QLQ-C30 GHS/QoL combined score was compared between treatment arms based on a cLDA model with the EORTC-QLQ-C30 GHS/QoL scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma).p-value: 0.48195% CI: [-6.71, 3.17]constrained Longitudinal Data Analysis
Secondary
Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants With ESCC
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.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study treatment, completed at least 1 EORTC-QLQ-C30 assessment, and who had ESCC were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembrolizumab + SOC | Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants With ESCC | -2.00 Score on a Scale |
| Placebo + SOC | Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants With ESCC | -1.94 Score on a Scale |
Comparison: Change from baseline to Week 18 in EORTC-QLQ-C30 GHS/QoL combined score was compared between treatment arms based on a cLDA model with the EORTC-QLQ-C30 GHS/QoL scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).p-value: 0.974295% CI: [-3.93, 3.81]constrained Longitudinal Data Analysis
Secondary
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)
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.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study treatment, completed at least 1 EORTC-QLQ-C30 assessment, who had ESCC, and who were PD-L1 CPS ≥10 were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembrolizumab + SOC | 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) | -2.36 Score on a Scale |
| Placebo + SOC | 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) | -0.40 Score on a Scale |
Comparison: Change from baseline to Week 18 in EORTC-QLQ-C30 GHS/QoL combined score was compared between treatment arms based on a cLDA model with the EORTC-QLQ-C30 GHS/QoL scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).p-value: 0.505395% CI: [-7.72, 3.82]constrained Longitudinal Data Analysis
Secondary
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
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.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study treatment and completed at least 1 EORTC-QLQ-C30 assessment were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembrolizumab + SOC | 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 | -1.74 Score on a Scale |
| Placebo + SOC | 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 | -1.64 Score on a Scale |
Comparison: Change from baseline to Week 18 in EORTC-QLQ-C30 GHS/QoL combined score was compared between treatment arms based on a constrained longitudinal data analysis (cLDA) model with the EORTC-QLQ-C30 GHS/QoL scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma) and ECOG performance status (0 versus 1).p-value: 0.95395% CI: [-3.4, 3.2]constrained Longitudinal Data Analysis
Secondary
DOR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
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.
Time frame: Up to approximately 34 months
Population: All randomized participants (ITT population) who were PD-L1 CPS ≥10 and who demonstrated a confirmed CR or PR were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + SOC | DOR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | 10.4 Months |
| Placebo + SOC | DOR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | 5.6 Months |
Secondary
DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC
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.
Time frame: Up to approximately 34 months
Population: All randomized participants (ITT population) with ESCC who demonstrated a confirmed CR or PR were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + SOC | DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC | 9.1 Months |
| Placebo + SOC | DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC | 6.1 Months |
Secondary
DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
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.
Time frame: Up to approximately 34 months
Population: All randomized participants (ITT population) with ESCC and PD-L1 CPS ≥10 who demonstrated a confirmed CR or PR were analyzed were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + SOC | DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | 10.4 Months |
| Placebo + SOC | DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | 4.4 Months |
Secondary
Duration of Response (DOR) Per RECIST 1.1 As Assessed By Investigator in All Participants
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.
Time frame: Up to approximately 34 months
Population: All randomized participants (ITT population) who demonstrated a confirmed CR or PR were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + SOC | Duration of Response (DOR) Per RECIST 1.1 As Assessed By Investigator in All Participants | 8.3 Months |
| Placebo + SOC | Duration of Response (DOR) Per RECIST 1.1 As Assessed By Investigator in All Participants | 6.0 Months |
Secondary
Number of Participants Discontinuing Study Treatment Due to an AE
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.
Time frame: Up to approximately 27 months
Population: All randomized participants who received at least one dose of study treatment were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab + SOC | Number of Participants Discontinuing Study Treatment Due to an AE | 90 Participants |
| Placebo + SOC | Number of Participants Discontinuing Study Treatment Due to an AE | 74 Participants |
Secondary
Number of Participants With an Adverse Event (AE)
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.
Time frame: Up to approximately 28 months
Population: All randomized participants who received at least one dose of study treatment were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab + SOC | Number of Participants With an Adverse Event (AE) | 370 Participants |
| Placebo + SOC | Number of Participants With an Adverse Event (AE) | 368 Participants |
Secondary
Objective Response Rate (ORR) Per RECIST 1.1 As Assessed By Investigator in All Participants
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).
Time frame: Up to approximately 34 months
Population: All randomized participants (ITT population) were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + SOC | Objective Response Rate (ORR) Per RECIST 1.1 As Assessed By Investigator in All Participants | 45.0 Percentage of Participants |
| Placebo + SOC | Objective Response Rate (ORR) Per RECIST 1.1 As Assessed By Investigator in All Participants | 29.3 Percentage of Participants |
Comparison: ORR in all participants of the pembrolizumab + SOC arm was compared to ORR in all participants of the placebo + SOC arm based on the Miettinen \& Nurminen method stratified by geographic region (Asia versus Rest of the World), tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma), and ECOG performance status (0 versus 1).p-value: <0.000195% CI: [9, 22.5]One-sided p-value
Secondary
ORR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
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.
Time frame: Up to approximately 34 months
Population: All randomized participants (ITT population) who were PD-L1 CPS ≥10 were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + SOC | ORR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | 51.1 Percentage of Participants |
| Placebo + SOC | ORR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | 26.9 Percentage of Participants |
Comparison: ORR in PD-L1 CPS ≥10 participants of the pembrolizumab + SOC arm was compared to ORR in PD-L1 CPS ≥10 participants of the placebo + SOC arm based on the Miettinen \& Nurminen method stratified by geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma).p-value: <0.000195% CI: [14.3, 33.2]One-sided p-value
Secondary
ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC
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.
Time frame: Up to approximately 34 months
Population: All randomized participants (ITT population) with ESCC were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + SOC | ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC | 43.8 Percentage of Participants |
| Placebo + SOC | ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC | 31.0 Percentage of Participants |
Comparison: ORR in ESCC participants of the pembrolizumab + SOC arm was compared to ORR in ESCC participants of the placebo + SOC arm based on the Miettinen \& Nurminen method stratified by geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).p-value: 0.000995% CI: [4.7, 20.7]One-sided p-value
Secondary
ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
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.
Time frame: Up to approximately 34 months
Population: All randomized participants (ITT population) with ESCC and PD-L1 CPS ≥10 were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + SOC | ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | 51.0 Percentage of Participants |
| Placebo + SOC | ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10) | 28.0 Percentage of Participants |
Comparison: ORR in ESCC PD-L1 CPS ≥10 participants of the pembrolizumab + SOC arm was compared to ORR in ESCC PD-L1 CPS ≥10 participants of the placebo + SOC arm based on the Miettinen \& Nurminen method stratified by geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).p-value: <0.000195% CI: [11.6, 33.4]One-sided p-value