A Study of Pembrolizumab (MK-3475) in Participants With Recurrent or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (MK-3475-059/KEYNOTE-059)
- Conditions
- Gastric AdenocarcinomaGastroesophageal Junction Adenocarcinoma
- Interventions
- Registration Number
- NCT02335411
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This is a study of pembrolizumab (MK-3475) for advanced gastric or gastroesophageal junction adenocarcinoma; pembrolizumab will be given as monotherapy to participants who have had previous treatment or who are treatment-naïve; pembrolizumab will also be evaluated as combination therapy with cisplatin and 5-Fluorouracil (5-FU) or (Japan only) capecitabine in treatment-naïve participants. The primary study hypothesis is that pembrolizumab will provide a clinically meaningful Overall Response Rate (ORR).
- Detailed Description
This study will have 3 cohorts. In Cohort 1, participants who have received at least two prior therapies for their advanced disease will receive monotherapy with pembrolizumab. In Cohort 2, participants who have not received any previous therapy for their disease will receive pembrolizumab in combination with cisplatin and 5-FU or (Japan only) capecitabine. In Cohort 3, participants who have not received any previous therapy and who have programmed death ligand 1 (PD-L1)-positive tumors will receive pembrolizumab monotherapy.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 318
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1: Pembrolizumab monotherapy, previously treated pembrolizumab Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) Cohort 3: Pembrolizumab monotherapy, treatment naive, PD-L1 positive pembrolizumab Programmed death-ligand 1 (PD-L1) positive participants receive pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) Cohort 2: Pembrolizumab combination therapy, treatment naive pembrolizumab Participants receive pembrolizumab 200 mg IV each 3-week cycle (Q3W) + cisplatin 80 mg/m\^2 IV Q3W for up to 6 cycles + 5-FU 800 mg/m\^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m\^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle Cohort 2: Pembrolizumab combination therapy, treatment naive 5-FU Participants receive pembrolizumab 200 mg IV each 3-week cycle (Q3W) + cisplatin 80 mg/m\^2 IV Q3W for up to 6 cycles + 5-FU 800 mg/m\^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m\^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle Cohort 2: Pembrolizumab combination therapy, treatment naive cisplatin Participants receive pembrolizumab 200 mg IV each 3-week cycle (Q3W) + cisplatin 80 mg/m\^2 IV Q3W for up to 6 cycles + 5-FU 800 mg/m\^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m\^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle Cohort 2: Pembrolizumab combination therapy, treatment naive capecitabine Participants receive pembrolizumab 200 mg IV each 3-week cycle (Q3W) + cisplatin 80 mg/m\^2 IV Q3W for up to 6 cycles + 5-FU 800 mg/m\^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m\^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) For All Participants in Cohorts 1 and 3 Up to approximately 75 months The Objective Response Rate (ORR) was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by central radiology review. The percentage of all participants (regardless of programmed death-ligand 1 \[PD-L1\] tumor status) in Cohorts 1 and 3 who had a CR or PR during first course pembrolizumab treatment per protocol, is presented.
Number of Participants Discontinuing Study Drug Due to AEs Up to approximately 52 months An AE was defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. The number of participants who discontinued study drug due to an AE is presented. Per protocol, the number of participants who discontinued drug during first course pembrolizumab treatment is presented.
Objective Response Rate For PD-L1 Positive Participants in Cohorts 1 and 3 Up to approximately 75 months The ORR was defined as the percentage of participants in the analysis population who had a CR or PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, as assessed by central radiology review. The percentage of all participants in Cohorts 1 and 3 with PD-L1+ tumor status who experienced a CR or PR during first course pembrolizumab treatment per protocol, is presented. Note: All participants in Cohort 3 had a PD-L1-positive tumor status.
Number of Participants Experiencing Adverse Events (AEs) Up to approximately 65 months An AE is defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. The number of participants who experienced at least one AE is presented. Per protocol, the number of participants who experienced at least one AE during first course pembrolizumab treatment is presented.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) For All Participants Up to approximately 75 months Duration of Response (DOR) was defined as the time from first documented evidence of CR or PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, based on central imaging vendor assessment, until disease progression (PD) or death, whichever occurred first. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. The DOR for all participants (regardless of PD-L1 tumor status) during first course pembrolizumab treatment per protocol, is presented.
Overall Survival (OS) For All Participants Up to approximately 75 months Overall Survival (OS) 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. The OS for all participants (regardless of PD-L1 tumor status) during first course pembrolizumab treatment per protocol, is presented.
Objective Response Rate For PD-L1 Positive Participants in Cohort 2 Up to approximately 75 months The ORR was defined as the percentage of participants in the analysis population who had a CR or PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, as assessed by central radiology review. The percentage of participants in Cohort 2 with PD-L1+ tumor status who experienced a CR or PR during first course pembrolizumab treatment per protocol, is presented.
Overall Survival For PD-L1 Positive Participants Up to approximately 75 months OS 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. The OS for only PD-L1 positive participants during first course pembrolizumab treatment per protocol, is presented. Note: All participants in Cohort 3 had a PD-L1-positive tumor status.
Objective Response Rate (ORR) For All Participants in Cohort 2 Up to approximately 75 months The Objective Response Rate (ORR) was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by central radiology review. The percentage of all participants (regardless of PD-L1 tumor status) in Cohort 2 who had a CR or PR during first course pembrolizumab treatment per protocol, is presented.
Disease Control Rate (DCR) For All Participants Up to approximately 75 months Disease Control Rate (DCR) was defined as the percentage of participants in the analysis population who had a CR or a PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) or stable disease (SD); (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) for ≥6 months, (for Cohort 1 ≥2 months) as assessed by central radiology review. The percentage of all participants (regardless of PD-L1 tumor status) who had a CR or PR or SD during first course pembrolizumab treatment per protocol, is presented.
Progression-Free Survival (PFS) For All Participants Up to approximately 75 months Progression-Free Survival (PFS) was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. The PFS for all participants (regardless of PD-L1 tumor status) during first course pembrolizumab treatment per protocol, is presented.
Duration of Response For PD-L1 Positive Participants Up to approximately 75 months DOR was defined as the time from first documented evidence of CR or PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, based on central imaging vendor assessment, until disease progression (PD) or death, whichever occurred first. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. The DOR for only PD-L1 positive participants during first course pembrolizumab treatment per protocol, is presented. Note: All participants in Cohort 3 had a PD-L1-positive tumor status.
Progression-Free Survival For PD-L1 Positive Participants Up to approximately 75 months PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. The PFS for only PD-L1 positive participants during first course pembrolizumab treatment per protocol, is presented. Note: All participants in Cohort 3 had a PD-L1-positive tumor status.
Disease Control Rate For PD-L1 Positive Participants Up to approximately 75 months DCR was defined as the percentage of participants in the analysis population who had a CR or a PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) or stable disease (SD); (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) for ≥6 months, (for Cohort 1 ≥2 months) as assessed by central radiology review. The percentage of participants with PD-L1+ tumor status who experienced a CR or PR or SD during first course pembrolizumab treatment per protocol, is presented. Note: All participants in Cohort 3 had a PD-L1-positive tumor status.