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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03615326




Registration number
NCT03615326
Ethics application status
Date submitted
31/07/2018
Date registered
3/08/2018
Date last updated
25/09/2020

Titles & IDs
Public title
Pembrolizumab/Placebo Plus Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-811/KEYNOTE-811)
Scientific title
A Phase III, Randomized, Double-blind Trial Comparing Trastuzumab Plus Chemotherapy and Pembrolizumab With Trastuzumab Plus Chemotherapy and Placebo as First-line Treatment in Participants With HER2 Positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (KEYNOTE 811)
Secondary ID [1] 0 0
2018-000224-34
Secondary ID [2] 0 0
3475-811
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastric Neoplasms 0 0
Gastroesophageal Junction Adenocarcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Oesophageal (gullet)
Cancer 0 0 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Pembrolizumab
Other interventions - Placebo
Treatment: Drugs - Cisplatin
Treatment: Drugs - 5-FU
Treatment: Drugs - Oxaliplatin
Treatment: Drugs - Capecitabine
Treatment: Drugs - S-1
Other interventions - Trastuzumab

Experimental: Pembrolizumab +Trastuzumab + Chemotherapy - Participants receive 200 mg pembrolizumab IV every 3 weeks (Q3W) plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with FP or CAPOX chemotherapy (Global Cohort) or SOX chemotherapy (Japan cohort).

Active Comparator: Placebo +Trastuzumab + Chemotherapy - Participants receive matched placebo to pembrolizumab IV Q3W plus trastuzumab (8mg/kg loading dose, 6mg/kg maintenance thereafter) IV Q3W in combination with FP or CAPOX chemotherapy (Global Cohort) or SOX chemotherapy (Japan cohort).


Other interventions: Pembrolizumab
200 mg on Day 1 of each 3-week cycle as an IV infusion.

Other interventions: Placebo
Solution for IV infusion on Day 1 of each 3-week cycle.

Treatment: Drugs: Cisplatin
80 mg/m^2 on Day 1 of each 3-week cycle as an IV infusion, administered as part of FP chemotherapy regimen.

Treatment: Drugs: 5-FU
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.

Treatment: Drugs: Oxaliplatin
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.

Treatment: Drugs: Capecitabine
1000 mg/m^2 as oral capsules BID on Days 1-14 of each 3-week cycle, administered as part of CAPOX chemotherapy regimen.

Treatment: Drugs: S-1
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.

Other interventions: Trastuzumab
8 mg/kg loading dose and then 6 mg/kg maintenance dose administered IV on day 1 of each 3-week cycle.

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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 will be determined for each treatment arm.
Timepoint [1] 0 0
Up to 4 years
Primary outcome [2] 0 0
Overall Survival (OS) - OS is defined as the time from randomization to death due to any cause. OS will be determined for each treatment arm.
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [1] 0 0
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 BICR. ORR will be determined for each treatment arm.
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [2] 0 0
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 will be determined for each treatment arm.
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
Adverse Events (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 experience an AE will be reported for each treatment arm.
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
Treatment Discontinuations 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 discontinue study treatment due to an AE will be reported for each treatment arm.
Timepoint [4] 0 0
Up to 5 years

Eligibility
Key inclusion criteria
- Histologically or cytologically confirmed diagnosis of previously untreated, locally
advanced unresectable or metastatic HER2 positive gastric or GEJ adenocarcinoma

- HER2-positive defined as either immunohistochemistry (IHC) 3+ or IHC 2+ in combination
with in-situ hybridization positive (ISH+) or fluorescent in-situ hybridization
(FISH), as assessed by central review on primary or metastatic tumor

- Has measurable disease as defined by RECIST 1.1 as determined by the site investigator

- Male participants must agree to use approved contraception

- Female participants who are not pregnant or breastfeeding, and who are either not a
woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved
contraception

- Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
Performance Scale within 3 days prior to the first dose of trial treatment

- Has a life expectancy of greater than 6 months

- Has adequate organ function
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ
cancer

- 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 had radiotherapy within 14 days of randomization

- Has a known additional malignancy that is progressing or has required active treatment
within the past 5 years

- Has known active central nervous system (CNS) 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

- Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis

- Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis)

- Has an active infection requiring systemic therapy

- Has poorly controlled diarrhea

- Accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic
drugs within 2 weeks prior to enrollment. If the participant is receiving diuretic
drugs for other reasons, it is acceptable

- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the participant's
participation for the full duration of the trial, or is not in the best interest of
the participant to participate, in the opinion of the treating investigator

- Has peripheral neuropathy > Grade 1

- Has a known psychiatric or substance abuse disorder that would interfere with
cooperation with the requirements of the trial

- A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization
or treatment allocation

- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 7 months
after the last dose of trial treatment

- Has active or clinically significant cardiac disease

- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)

- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection

- Has severe hypersensitivity (=Grade 3) to pembrolizumab, trastuzumab, study
chemotherapy agents and/or to any excipients, murine proteins, or platinum-containing
products

- Has had an allogeneic tissue/solid organ transplant

- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, Cluster of
Differentiation 137 [CD137])

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital ( Site 2206) - Liverpool
Recruitment hospital [2] 0 0
Westmead Hospital ( Site 2200) - Westmead
Recruitment hospital [3] 0 0
Southern Medical Day Care Centre ( Site 2207) - Wollongong
Recruitment hospital [4] 0 0
Monash Health ( Site 2202) - Clayton
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
2500 - Wollongong
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
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United States of America
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Georgia
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United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
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United States of America
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Minnesota
Country [7] 0 0
United States of America
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Missouri
Country [8] 0 0
United States of America
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New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
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North Carolina
Country [11] 0 0
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Oklahoma
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Pennsylvania
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South Dakota
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Texas
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United States of America
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Virginia
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United States of America
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Washington
Country [17] 0 0
Brazil
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Bahia
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Brazil
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Ceara
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Brazil
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Parana
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Brazil
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Rio Grande Do Sul
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Brazil
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Santa Catarina
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Brazil
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Rio de Janeiro
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Brazil
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Sao Paulo
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Chile
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Araucania
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Chile
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Maule
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Chile
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Region M. De Santiago
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Chile
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Region Metropolitana
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China
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Beijing
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Fujian
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Guangdong
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Heilongjiang
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Henan
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Jilin
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Zhejiang
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Finistere
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Nord
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Germany
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Baden-Wurttemberg
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Niedersachsen
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Sachsen
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Berlin
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Bremen
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Hamburg
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Quetzaltenango
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Ireland
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Dublin
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Israel
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Southern
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Israel
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Tell Abib
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Israel
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Yerushalayim
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Israel
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Kfar-Saba
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Israel
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Petah Tikva
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Israel
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?eifa
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Italy
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Bergamo
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Italy
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Catanzaro
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Milano
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Italy
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Modena
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Italy
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Napoli
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Italy
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Padova
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Italy
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Pescara
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Italy
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Pisa
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Aichi
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Chiba
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Ehime
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Gunma
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Hyogo
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Ibaraki
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Kagawa
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Japan
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Kanagawa
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Japan
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Miyagi
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Japan
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Osaka
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Japan
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Saitama
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Japan
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Shizuoka
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Japan
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Tochigi
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Japan
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Tokyo
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Japan
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Fukuoka
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Japan
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Gifu
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Japan
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Hiroshima
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Japan
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Kumamoto
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Japan
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Niigata
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Korea, Republic of
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Seoul
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New Zealand
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Auckland
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Poland
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Dolnoslaskie
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Poland
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Lubelskie
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Poland
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Mazowieckie
Country [95] 0 0
Poland
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Pomorskie
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Poland
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Slaskie
Country [97] 0 0
Poland
State/province [97] 0 0
Wielkopolskie
Country [98] 0 0
Russian Federation
State/province [98] 0 0
Baskortostan, Respublika
Country [99] 0 0
Russian Federation
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Chelyabinskaya Oblast
Country [100] 0 0
Russian Federation
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Moskva
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Russian Federation
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Samarskaya Oblast
Country [102] 0 0
Russian Federation
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Sankt-Peterburg
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Russian Federation
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Saint Petersburg
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Spain
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Alicante
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Spain
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Asturias
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Spain
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Barcelona
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Spain
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Cantabria
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Spain
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Madrid
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Turkey
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Adana
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Turkey
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Ankara
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Turkey
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Edirne
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Turkey
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Erzurum
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Turkey
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Istanbul
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Turkey
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Izmir
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Turkey
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Malatya
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Turkey
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Sakarya
Country [117] 0 0
Ukraine
State/province [117] 0 0
Dnipropetrovska Oblast
Country [118] 0 0
Ukraine
State/province [118] 0 0
Ivano-Frankivska Oblast
Country [119] 0 0
Ukraine
State/province [119] 0 0
Kharkivska Oblast
Country [120] 0 0
Ukraine
State/province [120] 0 0
Kyivska Oblast
Country [121] 0 0
Ukraine
State/province [121] 0 0
Lvivska Oblast
Country [122] 0 0
Ukraine
State/province [122] 0 0
Odeska Oblast
Country [123] 0 0
Ukraine
State/province [123] 0 0
Zaporizka Oblast
Country [124] 0 0
United Kingdom
State/province [124] 0 0
Dundee City
Country [125] 0 0
United Kingdom
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East Riding Of Yorkshire
Country [126] 0 0
United Kingdom
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London, City Of
Country [127] 0 0
United Kingdom
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Surrey
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United Kingdom
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Derby
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United Kingdom
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Manchester
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United Kingdom
State/province [130] 0 0
Northwood
Country [131] 0 0
United Kingdom
State/province [131] 0 0
Walsall

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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).
Trial website
https://clinicaltrials.gov/show/NCT03615326
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03615326