Gastric AdenocarcinomaPhase 2NCT02335411

A Study of Pembrolizumab (MK-3475) in Participants With Recurrent or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (MK-3475-059/KEYNOTE-059)

A Phase 2 study testing pembrolizumab, cisplatin and 5-FU in people with Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma
What is being tested?: pembrolizumab, cisplatin and 5-FU
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 318 participants
Where: No sites listed yet
Study dates: 3 Feb 2015to 23 Jul 2021
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Received and progressed on ≥2 prior chemotherapy regimens for their advanced disease; prior regimen must have included a cisplatin and a fluoropyridine
Human epidermal growth factor receptor 2 (HER-2/neu) negative, or, if HER2/neu positive, must have previously received treatment with trastuzumab
HER2/neu negative
Has not received prior systemic anti-cancer therapy for their advanced carcinoma (systemic therapy received in the neoadjuvant and adjuvant setting does not count)
Histologically- or cytologically-confirmed recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma that is considered incurable by local therapies
Willing to provide tissue for PD-L1 biomarker analysis from newly-obtained and/or archival tissue

Show all 12Show fewer

Measurable disease based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 3 days prior to first dose of study drug
Life expectancy of at least 3 months
Female participants of childbearing potential should have a negative pregnancy test and be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study drug (180 days for participants receiving cisplatin + 5FU)
Male participants should agree to use an adequate method of contraception starting with the first dose through 120 days after the last dose of study drug (180 days for participants receiving cisplatin + 5FU)
Adequate organ function

Who cannot join

Currently participating and receiving study therapy or participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of study drug
Active autoimmune disease that has required systemic treatment in past 2 years
Immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
Weight loss >10% over 2 months prior to first dose of study drug
Clinical evidence of ascites by physical exam
Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered from AEs due to agents administered more than 4 weeks earlier

Show all 17Show fewer

Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered from AEs due to a previously administered agent
Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Known history of, or any evidence of active, non-infectious pneumonitis
Active infection requiring systemic therapy
Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
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 drug (180 days for participants receiving cisplatin + 5FU)
Prior therapy with an anti-programmed death-1 (PD-1), anti-PD-L1, or anti-PD-L2 agent
Human immunodeficiency virus (HIV)
Hepatitis B or C
Received live vaccine within 30 days of planned start of study drug

About this study

Official title: A Phase II Clinical Trial of Pembrolizumab as Monotherapy and in Combination With Cisplatin+5-Fluorouracil in Subjects With Recurrent or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (KEYNOTE-059)

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).

Read the 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.

Conditions: Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma
Being tested: pembrolizumab, cisplatin, 5-FU, capecitabine
Keywords: Gastric cancer, Gastroesophageal junction cancer, Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Medical subject headings: Stomach Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

pembrolizumabBiological
Also called MK-3475
IV infusion
cisplatinDrug
Also called PLATINOL®
IV infusion
5-FUDrug
Also called ADRUCIL®
IV infusion
capecitabineDrug
Also called XELODA®
oral tablets

Study groups in NCT02335411
Study group	Role	What they receive
Cohort 1: Pembrolizumab monotherapy, previously treated	Experimental	Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) Receives: Biological: pembrolizumab
Cohort 2: Pembrolizumab combination therapy, treatment naive	Experimental	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 Receives: Biological: pembrolizumab; Drug: cisplatin; Drug: 5-FU; Drug: capecitabine
Cohort 3: Pembrolizumab monotherapy, treatment naive, PD-L1 positive	Experimental	Programmed death-ligand 1 (PD-L1) positive participants receive pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) Receives: Biological: pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants Experiencing Adverse Events (AEs)
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.
Measured: Up to approximately 65 months
Number of Participants Discontinuing Study Drug Due to AEs
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.
Measured: Up to approximately 52 months
Objective Response Rate (ORR) For All Participants in Cohorts 1 and 3
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.
Measured: Up to approximately 75 months
Objective Response Rate For PD-L1 Positive Participants in Cohorts 1 and 3
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.
Measured: Up to approximately 75 months

Secondary outcomes (10)

Objective Response Rate (ORR) For All Participants in Cohort 2
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.
Measured: Up to approximately 75 months
Objective Response Rate For PD-L1 Positive Participants in Cohort 2
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.
Measured: Up to approximately 75 months
Duration of Response (DOR) For All Participants
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.
Measured: Up to approximately 75 months
Duration of Response For PD-L1 Positive Participants
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.
Measured: Up to approximately 75 months
Progression-Free Survival (PFS) For All Participants
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.
Measured: Up to approximately 75 months
Progression-Free Survival For PD-L1 Positive Participants
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.
Measured: Up to approximately 75 months
Overall Survival (OS) For All Participants
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.
Measured: Up to approximately 75 months
Overall Survival For PD-L1 Positive Participants
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.
Measured: Up to approximately 75 months
Disease Control Rate (DCR) For All Participants
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.
Measured: Up to approximately 75 months
Disease Control Rate For PD-L1 Positive Participants
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.
Measured: Up to approximately 75 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Feb 201523 Jul 2021

First posted9 Jan 2015 (estimated)
Study start3 Feb 2015
Primary completion23 Jul 2021
Study completion23 Jul 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (7)Papers the sponsor has linked to this study.
Other trials for Gastric AdenocarcinomaStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 318 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02335411
Sponsor's protocol ID: 3475-059
Other IDs: MK-3475-059, KEYNOTE-059, 2014-003574-16, 2014
Status last verified: Jul 2022
First submitted: 7 Jan 2015
Last updated: 8 Aug 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

Janjigian YY, Cecchini M, Shitara K, Enzinger PC, Wainberg ZA, Chau I, Satoh T, Lee J, Nebozhyn M, Loboda A, Kobie J, Vajdi A, Shih CS, Cristescu R, Cao ZA. Genomic Landscape of Late-Stage Gastric Cancer: Analysis From KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 Studies. JCO Precis Oncol. 2025 Mar;9:e2400456. doi: 10.1200/PO-24-00456. Epub 2025 Mar 21.
PubMed 40117530
Topp BG, Channavazzala M, Mayawala K, De Alwis DP, Rubin E, Snyder A, Wolchok JD, Ribas A. Tumor dynamics in patients with solid tumors treated with pembrolizumab beyond disease progression. Cancer Cell. 2023 Sep 11;41(9):1680-1688.e2. doi: 10.1016/j.ccell.2023.08.004.
PubMed 37699333
Muro K, Shitara K, Yamaguchi K, Yoshikawa T, Satake H, Hara H, Sugimoto N, Machida N, Goto M, Kawakami H, Amagai K, Omuro Y, Esaki T, Hironaka S, Nishina T, Komatsu Y, Matsubara H, Shiratori S, Han S, Satoh T, Ohtsu A. Efficacy of Pembrolizumab Monotherapy in Japanese Patients with Advanced Gastric or Gastroesophageal Junction Cancer. J Gastrointest Cancer. 2023 Sep;54(3):951-961. doi: 10.1007/s12029-023-00920-9. Epub 2023 Apr 10.
PubMed 37037952
Cristescu R, Aurora-Garg D, Albright A, Xu L, Liu XQ, Loboda A, Lang L, Jin F, Rubin EH, Snyder A, Lunceford J. Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors. J Immunother Cancer. 2022 Jan;10(1):e003091. doi: 10.1136/jitc-2021-003091.
PubMed 35101941
Chao J, Fuchs CS, Shitara K, Tabernero J, Muro K, Van Cutsem E, Bang YJ, De Vita F, Landers G, Yen CJ, Chau I, Elme A, Lee J, Ozguroglu M, Catenacci D, Yoon HH, Chen E, Adelberg D, Shih CS, Shah S, Bhagia P, Wainberg ZA. Assessment of Pembrolizumab Therapy for the Treatment of Microsatellite Instability-High Gastric or Gastroesophageal Junction Cancer Among Patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 Clinical Trials. JAMA Oncol. 2021 Jun 1;7(6):895-902. doi: 10.1001/jamaoncol.2021.0275.
PubMed 33792646
Bang YJ, Kang YK, Catenacci DV, Muro K, Fuchs CS, Geva R, Hara H, Golan T, Garrido M, Jalal SI, Borg C, Doi T, Yoon HH, Savage MJ, Wang J, Dalal RP, Shah S, Wainberg ZA, Chung HC. Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study. Gastric Cancer. 2019 Jul;22(4):828-837. doi: 10.1007/s10120-018-00909-5. Epub 2019 Mar 25.
PubMed 30911859
Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH. Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncol. 2018 May 10;4(5):e180013. doi: 10.1001/jamaoncol.2018.0013. Epub 2018 May 10.
PubMed 29543932

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
RecruitingPhase 2
Perioperative Chemotherapy With Low-Dose Radiotherapy and Tislelizumab for Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Gastric or Gastroesophageal Junction Adenocarcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma

All Gastric Adenocarcinoma trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II Clinical Trial of Pembrolizumab as Monotherapy and in Combination With Cisplatin+5-Fluorouracil in Subjects With Recurrent or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (KEYNOTE-059)
ClinicalTrials.gov ID: NCT02335411
Acronym / sponsor ID: 3475-059
Conditions: Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma
Keywords: Gastric cancer, Gastroesophageal junction cancer, Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 318 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 3 Feb 2015 (actual)
Primary completion: 23 Jul 2021 (actual)
Study completion: 23 Jul 2021 (actual)
First posted: 9 Jan 2015 (estimated)
Results: Posted 8 Aug 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Cohort 1: Pembrolizumab monotherapy, previously treated	Experimental	Biological: pembrolizumabParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W)
Cohort 2: Pembrolizumab combination therapy, treatment naive	Experimental	Biological: pembrolizumab, Drug: cisplatin, Drug: 5-FU, Drug: capecitabineParticipants 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 3: Pembrolizumab monotherapy, treatment naive, PD-L1 positive	Experimental	Biological: pembrolizumabProgrammed death-ligand 1 (PD-L1) positive participants receive pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Received and progressed on ≥2 prior chemotherapy regimens for their advanced disease; prior regimen must have included a cisplatin and a fluoropyridine
Human epidermal growth factor receptor 2 (HER-2/neu) negative, or, if HER2/neu positive, must have previously received treatment with trastuzumab
HER2/neu negative
Has not received prior systemic anti-cancer therapy for their advanced carcinoma (systemic therapy received in the neoadjuvant and adjuvant setting does not count)
Histologically- or cytologically-confirmed recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma that is considered incurable by local therapies

Key exclusion criteria (17 listed)

Currently participating and receiving study therapy or participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of study drug
Active autoimmune disease that has required systemic treatment in past 2 years
Immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
Weight loss >10% over 2 months prior to first dose of study drug
Clinical evidence of ascites by physical exam

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
pembrolizumabAlso: MK-3475IV infusion	Biological	Cohort 1: Pembrolizumab monotherapy, previously treated, Cohort 2: Pembrolizumab combination therapy, treatment naive, Cohort 3: Pembrolizumab monotherapy, treatment naive, PD-L1 positive
cisplatinAlso: PLATINOL®IV infusion	Drug	Cohort 2: Pembrolizumab combination therapy, treatment naive
5-FUAlso: ADRUCIL®IV infusion	Drug	Cohort 2: Pembrolizumab combination therapy, treatment naive
capecitabineAlso: XELODA®oral tablets	Drug	Cohort 2: Pembrolizumab combination therapy, treatment naive

Primary outcome

Number of Participants Experiencing Adverse Events (AEs)
Time frame: 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.
Number of Participants Discontinuing Study Drug Due to AEs
Time frame: 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 (ORR) For All Participants in Cohorts 1 and 3
Time frame: 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.
Objective Response Rate For PD-L1 Positive Participants in Cohorts 1 and 3
Time frame: 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.

10 secondary outcomes

Objective Response Rate (ORR) For All Participants in Cohort 2
Time frame: Up to approximately 75 months
Objective Response Rate For PD-L1 Positive Participants in Cohort 2
Time frame: Up to approximately 75 months
Duration of Response (DOR) For All Participants
Time frame: Up to approximately 75 months
Duration of Response For PD-L1 Positive Participants
Time frame: Up to approximately 75 months
Progression-Free Survival (PFS) For All Participants
Time frame: Up to approximately 75 months
Progression-Free Survival For PD-L1 Positive Participants
Time frame: Up to approximately 75 months
Overall Survival (OS) For All Participants
Time frame: Up to approximately 75 months
Overall Survival For PD-L1 Positive Participants
Time frame: Up to approximately 75 months
Disease Control Rate (DCR) For All Participants
Time frame: Up to approximately 75 months
Disease Control Rate For PD-L1 Positive Participants
Time frame: Up to approximately 75 months

Results and safety

Results posted to the registry on 8 Aug 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1: Pembrolizumab Monotherapy, Previously Treated	259	0
Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive	25	0
Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive	31	0

Primary outcome: Number of Participants Experiencing Adverse Events (AEs)

Time frame: Up to approximately 65 months. Count of participants. Unit: Participants

Measure	Cohort 1: Pembrolizumab Monotherapy, Previously Treated n = 259	Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive n = 25	Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive n = 31
Value	248	25	31

Population analysed: All enrolled participants who received ≥1 dose of study drug.

Primary outcome: Number of Participants Discontinuing Study Drug Due to AEs

Time frame: Up to approximately 52 months. Count of participants. Unit: Participants

Measure	Cohort 1: Pembrolizumab Monotherapy, Previously Treated n = 259	Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive n = 25	Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive n = 31
Value	18	4	0

Population analysed: All enrolled participants who received ≥1 dose of study drug.

Primary outcome: Objective Response Rate (ORR) For All Participants in Cohorts 1 and 3

Time frame: Up to approximately 75 months. Number (95% Confidence Interval). Unit: Percentage of Participants

Measure	Cohort 1: Pembrolizumab Monotherapy, Previously Treated n = 259	Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive n = 0	Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive n = 31
Value	11.6 (8.0 to 16.1)	–	22.6 (9.6 to 41.1)

Population analysed: All enrolled participants in Cohorts 1 and 3 who received ≥1 dose of study drug. Per protocol, Cohort 2 was not included in this outcome measure.

Primary outcome: Objective Response Rate For PD-L1 Positive Participants in Cohorts 1 and 3

Time frame: Up to approximately 75 months. Number (95% Confidence Interval). Unit: Percentage of Participants

Measure	Cohort 1: Pembrolizumab Monotherapy, Previously Treated n = 148	Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive n = 0	Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive n = 31
Value	15.5 (10.1 to 22.4)	–	22.6 (9.6 to 41.1)

Population analysed: All enrolled participants in Cohorts 1 and 3 with a positive PD-L1 tumor status who received ≥1 dose of study drug. Per protocol, Cohort 2 was not included in this outcome measure.

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to approximately 75 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1 First Course	119 of 259 (45.9%)	237 of 259 (91.5%)	244 of 259
Cohort 2 First Course	11 of 25 (44%)	25 of 25 (100%)	21 of 25
Cohort 3 First Course	15 of 31 (48.4%)	31 of 31 (100%)	26 of 31
Cohort 1 Second Course	0 of 3 (0%)	0 of 3 (0%)	1 of 3
Cohort 2 Second Course	0 of 1 (0%)	0 of 1 (0%)	1 of 1
Cohort 3 Second Course	0 of 2 (0%)	0 of 2 (0%)	1 of 2

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40117530Janjigian YY, Cecchini M, Shitara K, Enzinger PC, Wainberg ZA, Chau I, Satoh T, Lee J, Nebozhyn M, Loboda A, Kobie J, Vajdi A, Shih CS, Cristescu R, Cao ZA. Genomic Landscape of Late-Stage Gastric Cancer: Analysis From KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 Studies. JCO Precis Oncol. 2025 Mar;9:e2400456. doi: 10.1200/PO-24-00456. Epub 2025 Mar 21.
Derived from this study: PubMed 37699333Topp BG, Channavazzala M, Mayawala K, De Alwis DP, Rubin E, Snyder A, Wolchok JD, Ribas A. Tumor dynamics in patients with solid tumors treated with pembrolizumab beyond disease progression. Cancer Cell. 2023 Sep 11;41(9):1680-1688.e2. doi: 10.1016/j.ccell.2023.08.004.
Derived from this study: PubMed 37037952Muro K, Shitara K, Yamaguchi K, Yoshikawa T, Satake H, Hara H, Sugimoto N, Machida N, Goto M, Kawakami H, Amagai K, Omuro Y, Esaki T, Hironaka S, Nishina T, Komatsu Y, Matsubara H, Shiratori S, Han S, Satoh T, Ohtsu A. Efficacy of Pembrolizumab Monotherapy in Japanese Patients with Advanced Gastric or Gastroesophageal Junction Cancer. J Gastrointest Cancer. 2023 Sep;54(3):951-961. doi: 10.1007/s12029-023-00920-9. Epub 2023 Apr 10.
Derived from this study: PubMed 35101941Cristescu R, Aurora-Garg D, Albright A, Xu L, Liu XQ, Loboda A, Lang L, Jin F, Rubin EH, Snyder A, Lunceford J. Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors. J Immunother Cancer. 2022 Jan;10(1):e003091. doi: 10.1136/jitc-2021-003091.
Derived from this study: PubMed 33792646Chao J, Fuchs CS, Shitara K, Tabernero J, Muro K, Van Cutsem E, Bang YJ, De Vita F, Landers G, Yen CJ, Chau I, Elme A, Lee J, Ozguroglu M, Catenacci D, Yoon HH, Chen E, Adelberg D, Shih CS, Shah S, Bhagia P, Wainberg ZA. Assessment of Pembrolizumab Therapy for the Treatment of Microsatellite Instability-High Gastric or Gastroesophageal Junction Cancer Among Patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 Clinical Trials. JAMA Oncol. 2021 Jun 1;7(6):895-902. doi: 10.1001/jamaoncol.2021.0275.
Derived from this study: PubMed 30911859Bang YJ, Kang YK, Catenacci DV, Muro K, Fuchs CS, Geva R, Hara H, Golan T, Garrido M, Jalal SI, Borg C, Doi T, Yoon HH, Savage MJ, Wang J, Dalal RP, Shah S, Wainberg ZA, Chung HC. Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study. Gastric Cancer. 2019 Jul;22(4):828-837. doi: 10.1007/s10120-018-00909-5. Epub 2019 Mar 25.
Derived from this study: PubMed 29543932Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH. Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncol. 2018 May 10;4(5):e180013. doi: 10.1001/jamaoncol.2018.0013. Epub 2018 May 10.
Merck Oncology Clinical Trials InformationLink provided by the sponsor.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Related trials for Gastric Adenocarcinoma

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
RecruitingPhase 2
Perioperative Chemotherapy With Low-Dose Radiotherapy and Tislelizumab for Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Gastric or Gastroesophageal Junction Adenocarcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing pembrolizumab, cisplatin and 5-FU in people with Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Experiencing Adverse Events (AEs) (time frame: Up to approximately 65 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02335411, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2022.