NCT03615326 · CITED IN SOURCE DOCUMENTS

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)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2026-08-26

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).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression Free Survival (PFS) Per RECIST 1.1 Assessed by BICR

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Objective Response Rate (ORR) Per RECIST 1.1 Assessed by BICR

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outcome · POSTED

Duration of Response (DOR) Per RECIST 1.1 Assessed by BICR

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outcome · POSTED

Number of Participants Who Experienced an Adverse Event (AE)

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outcome · POSTED

Number of Participants Who Discontinued Study Treatment Due to AEs

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: Inclusion criteria include, but are not limited to: * Histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2) positive gastric or gastroesophageal junction (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 Response Evaluation Criteria in Solid Tumors version 1.1 (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 Exclusion Criteria: Exclusion criteria include, but are not limited to: * 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 24 hours prior to randomization or treatment allocation * 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 \[CD137\])
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants received 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 investigator's choice of FP or CAPOX chemotherapy.
intervention Names
Biological: Pembrolizumab
Drug: Cisplatin
Drug: 5-FU
Drug: Oxaliplatin
Drug: Capecitabine
Biological: Trastuzumab
label
Global Pembrolizumab + Standard of Care First Course
type
EXPERIMENTAL
description
Participants received matched placebo to pembrolizumab IV Q3W plus trastuzumab (8mg/kg loading dose, 6mg/kg maintenance thereafter) IV Q3W in combination with investigator's choice of FP or CAPOX chemotherapy.
intervention Names
Biological: Placebo
Drug: Cisplatin
Drug: 5-FU
Drug: Oxaliplatin
Drug: Capecitabine
Biological: Trastuzumab
label
Global Standard of Care
type
ACTIVE_COMPARATOR
description
Participants received 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 SOX chemotherapy.
intervention Names
Biological: Pembrolizumab
Drug: Oxaliplatin
Drug: S-1
Biological: Trastuzumab
label
Japan Pembrolizumab + Trastuzumab + S-1 Plus Oxaliplatin
type
EXPERIMENTAL
description
Participants received matched placebo to pembrolizumab IV Q3W plus trastuzumab (8mg/kg loading dose, 6mg/kg maintenance thereafter) IV Q3W in combination with SOX chemotherapy.
intervention Names
Biological: Placebo
Drug: Oxaliplatin
Drug: S-1
Biological: Trastuzumab
label
Japan Trastuzumab + S-1 Plus Oxaliplatin
type
EXPERIMENTAL

interventions

arm Group Labels
Global Pembrolizumab + Standard of Care First Course
Japan Pembrolizumab + Trastuzumab + S-1 Plus Oxaliplatin
description
200 mg on Day 1 of each 3-week cycle as an IV infusion.
name
Pembrolizumab
other Names
Keytruda®
MK-3475
type
BIOLOGICAL
arm Group Labels
Global Standard of Care
Japan Trastuzumab + S-1 Plus Oxaliplatin
description
Solution for IV infusion on Day 1 of each 3-week cycle.
name
Placebo
type
BIOLOGICAL
arm Group Labels
Global Pembrolizumab + Standard of Care First Course
Global Standard of Care
description
80 mg/m\^2 on Day 1 of each 3-week cycle as an IV infusion, administered as part of FP chemotherapy regimen.
name
Cisplatin
type
DRUG
arm Group Labels
Global Pembrolizumab + Standard of Care First Course
Global Standard of Care
description
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.
name
5-FU
type
DRUG
arm Group Labels
Global Pembrolizumab + Standard of Care First Course
Global Standard of Care
Japan Pembrolizumab + Trastuzumab + S-1 Plus Oxaliplatin
Japan Trastuzumab + S-1 Plus Oxaliplatin
description
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.
name
Oxaliplatin
type
DRUG
arm Group Labels
Global Pembrolizumab + Standard of Care First Course
Global Standard of Care
description
1000 mg/m\^2 as oral capsules BID on Days 1-14 of each 3-week cycle, administered as part of CAPOX chemotherapy regimen.
name
Capecitabine
type
DRUG
arm Group Labels
Japan Pembrolizumab + Trastuzumab + S-1 Plus Oxaliplatin
Japan Trastuzumab + S-1 Plus Oxaliplatin
description
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.
name
S-1
type
DRUG
arm Group Labels
Global Pembrolizumab + Standard of Care First Course
Global Standard of Care
Japan Pembrolizumab + Trastuzumab + S-1 Plus Oxaliplatin
Japan Trastuzumab + S-1 Plus Oxaliplatin
description
8 mg/kg loading dose and then 6 mg/kg maintenance dose administered IV on day 1 of each 3-week cycle.
name
Trastuzumab
other Names
Herceptin®
type
BIOLOGICAL

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: QUADRUPLE
who Masked: PARTICIPANT
CARE_PROVIDER
INVESTIGATOR
OUTCOMES_ASSESSOR

primary Purpose

TREATMENT

Enrollment

count: 738
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Progression Free Survival (PFS) Per RECIST 1.1 Assessed by BICR
time Frame
Up to 46 months
description
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.
measure
Overall Survival (OS)
time Frame
Up to 63 months

secondary Outcomes

description
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.
measure
Objective Response Rate (ORR) Per RECIST 1.1 Assessed by BICR
time Frame
Up to 63 months
description
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.
measure
Duration of Response (DOR) Per RECIST 1.1 Assessed by BICR
time Frame
Up to 63 months
description
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.
measure
Number of Participants Who Experienced an Adverse Event (AE)
time Frame
Up to 63 months
description
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.
measure
Number of Participants Who Discontinued Study Treatment Due to AEs
time Frame
Up to 63 months

Full study description

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).
detailed Description: 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.

Source references

references

citation
Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, Yanez P, Wyrwicz LS, Shen L, Ostapenko Y, Bilici M, Chung HC, Shitara K, Qin SK, Van Cutsem E, Tabernero J, Li K, Shih CS, Bhagia P, Rha SY; KEYNOTE-811 Investigators. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023 Dec 9;402(10418):2197-2208. doi: 10.1016/S0140-6736(23)02033-0. Epub 2023 Oct 20.
pmid
37871604
type
RESULT
citation
Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, Yanez P, Wyrwicz LS, Shen L, Ostapenko Y, Bilici M, Chung HC, Shitara K, Qin S, Van Cutsem E, Tabernero J, Luo S, Mahave M, Tang Y, Lowery M, Monteiro MMF, Xu L, Shih CS, Sharan KP, Bhagia P, Rha SY. Pembrolizumab in HER2-Positive Gastric Cancer. N Engl J Med. 2024 Oct 10;391(14):1360-1362. doi: 10.1056/NEJMc2408121. Epub 2024 Sep 14. No abstract available.
pmid
39282917
type
RESULT
citation
Janjigian YY, Kawazoe A, Yanez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. doi: 10.1038/s41586-021-04161-3. Epub 2021 Dec 15.
pmid
34912120
type
DERIVED
citation
Chung HC, Bang YJ, S Fuchs C, Qin SK, Satoh T, Shitara K, Tabernero J, Van Cutsem E, Alsina M, Cao ZA, Lu J, Bhagia P, Shih CS, Janjigian YY. First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811. Future Oncol. 2021 Feb;17(5):491-501. doi: 10.2217/fon-2020-0737. Epub 2020 Nov 10.
pmid
33167735
type
DERIVED