The study will compare the efficacy and safety of pembrolizumab plus trastuzumab in combination with standard of care (SOC) chemotherapy versus trastuzumab in combination with SOC chemotherapy in participants with HER2-positive gastric cancer. The primary hypotheses of the study are that pembrolizumab plus trastuzumab in combination with chemotherapy is superior to trastuzumab plus chemotherapy in terms of 1) progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR), and 2) overall survival (OS).
Pembrolizumab (200 mg) or placebo will be administered intravenously \[IV\] on day 1 of each 3-week cycle. Trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance dose) will be administered IV on day 1 of each 3-week cycle. SOC chemotherapy for the global cohort will either be FP (80 mg/m\^2 cisplatin administered IV on Day 1 of each 3-week cycle and 800 mg/m\^2 5-fluorouracil \[5-FU\] administered IV on Days 1-5 of each 3-week cycle) or CAPOX (1000 mg/m\^2 capecitabine administered orally twice daily \[BID\] on days 1-14 of each 3-week cycle and 130 mg/m\^2 oxaliplatin administered IV on Day 1 of each 3-week cycle). A Japan cohort will receive SOX chemotherapy consisting of S-1 (tegafur, 5-chloro-2,4-dihydroxypyridine \[CDHP\], and potassium oxonate \[Oxo\]) administered orally BID according to Body Surface Area (BSA) on Days 1-14 of each 3-week cycle and oxaliplatin (130 mg/m\^2) administered IV on Day 1 each 3-week cycle.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
738
200 mg on Day 1 of each 3-week cycle as an IV infusion.
Solution for IV infusion on Day 1 of each 3-week cycle.
80 mg/m\^2 on Day 1 of each 3-week cycle as an IV infusion, administered as part of FP chemotherapy regimen.
800 mg/m\^2/day continuous on Days 1-5 of each 3-week cycle (120 hours or per local standard), administered as part of FP chemotherapy regimen.
130 mg/m\^2 on Day 1 of each 3-week cycle over 2 hours as an IV infusion, administered as part of CAPOX chemotherapy regimen and as part of SOX chemotherapy regimen.
1000 mg/m\^2 as oral capsules BID on Days 1-14 of each 3-week cycle, administered as part of CAPOX chemotherapy regimen.
Combination product of tegafur, CDHP, and Oxo. Oral capsules BID on Days 1-14 of each 3-week cycle based on body surface area (BSA): \<1.25 m\^2 BSA =40 mg, 1.25 to \<1.5 m\^2 BSA=50 mg, ≥1.5 m\^2 BSA=60 mg. Administered as part of SOX chemotherapy regimen.
8 mg/kg loading dose and then 6 mg/kg maintenance dose administered IV on day 1 of each 3-week cycle.
UCLA Hematology/Oncology - Westwood (Building 200 Suite 120) ( Site 0045)
Los Angeles, California, United States
Pacific Cancer Care ( Site 0063)
Monterey, California, United States
UC Irvine Medical Center/Chao Family Comprehensive Cancer Center ( Site 0050)
Orange, California, United States
University of Miami Sylvester Comprehensive Cancer Center - Plantation ( Site 0026)
Miami, Florida, United States
Southeastern Regional Medical Center, Inc. ( Site 0058)
Newnan, Georgia, United States
Progression Free Survival (PFS) Per RECIST 1.1 Assessed by BICR
PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 as assessed by BICR or death due to any cause, whichever occurs first. Per RECIST 1.1, progressive disease (PD) is 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 is also considered progression. PFS was determined for first course pembrolizumab in the Global Cohort. Per statistical analysis plan, participants in the Japan-specific SOX Cohort were not included in the efficacy analysis.
Time frame: Up to 46 months
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause. OS was determined for first course pembrolizumab in the Global Cohort. Per statistical analysis plan, participants in the Japan-specific SOX Cohort were not included in the efficacy analysis.
Time frame: Up to 63 months
Objective Response Rate (ORR) Per RECIST 1.1 Assessed by BICR
ORR is defined as the percentage of participants who have a Complete Response (\[CR\], disappearance of all evidence of disease) or Partial Response (\[PR\], regression of measurable disease and no new sites) per RECIST 1.1 as assessed by blinded independent central review (BICR). ORR was determined for first course pembrolizumab in the Global Cohort. Per statistical analysis plan, participants in the Japan-specific SOX Cohort were not included in the efficacy analysis.
Time frame: Up to 63 months
Duration of Response (DOR) Per RECIST 1.1 Assessed by BICR
For participants who demonstrate CR or PR, DOR is defined as the time from first response (CR or PR) to subsequent disease progression or death from any cause, whichever occurs first. DOR was determined for first course pembrolizumab in the Global Cohort. Per statistical analysis plan, participants in the Japan-specific SOX Cohort were not included in the efficacy analysis.
Time frame: Up to 63 months
Number of Participants Who Experienced an Adverse Event (AE)
An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experienced an AE is reported for each treatment arm. Per statistical analysis plan, data from the second course of pembrolizumab was not included in the safety analysis.
Time frame: Up to 63 months
Number of Participants Who Discontinued Study Treatment Due to AEs
An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who discontinued study treatment due to an AE is reported for each treatment arm. Per statistical analysis plan, data from the second course of pembrolizumab was not included in the safety analysis.
Time frame: Up to 63 months
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Midwestern Regional Medical Center, Inc. ( Site 0059)
Zion, Illinois, United States
Beth Israel Deaconess Medical Center ( Site 0070)
Boston, Massachusetts, United States
Dana-Farber Cancer Institute [Boston, MA] ( Site 0010)
Boston, Massachusetts, United States
Minnesota Oncology Hematology, PA ( Site 8001)
Minneapolis, Minnesota, United States
Washington University School of Medicine ( Site 0040)
St Louis, Missouri, United States
...and 182 more locations