Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo... | NCT04859582

ID	Type	Description
2018-001757-27	EudraCT Number
MK-3475-859 China Extension	Other Identifier	Merck
KEYNOTE-859	Other Identifier	Merck
194649	Registry Identifier	JAPIC-CTI

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Pembrolizumab + FP or CAPOX	Experimental	Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m^2 IV on Day 1 Q3W and 5-fluorouracil (5FU) 800 mg/m^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m^2 IV on Day 1 Q3W + capecitabine 1000 mg/m^2 orally twice a day (BID) on Days 1 to 14 Q3W. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).	Biological: Pembrolizumab Drug: Cisplatin Drug: 5-fluorouracil Drug: Oxaliplatin Drug: Capecitabine
Placebo + FP or CAPOX	Active Comparator	Participants receive placebo for pembrolizumab IV on Day 1 Q3W for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m^2 IV on Day 1 Q3W and 5FU 800 mg/m^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m^2 IV on Day 1 Q3W + capecitabine 1000 mg/m^2 orally BID on Days 1 to 14 Q3W.	Drug: Cisplatin Drug: 5-fluorouracil Drug: Oxaliplatin Drug: Capecitabine Drug: Placebo for Pembrolizumab

Name	Type	Description	Arm Group Labels	Other Names
Pembrolizumab	Biological	Administered as an IV infusion on Day 1 Q3W	Pembrolizumab + FP or CAPOX

Measure	Description	Time Frame
Overall Survival (OS)	OS is the time from randomization to death due to any cause.	Up to approximately 65 months

Measure	Description	Time Frame
Progression-free Survival (PFS)	PFS is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR).	Up to approximately 65 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria

Has histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma with known programmed cell death ligand 1 (PD-L1) expression status
Has human epidermal growth factor receptor 2 (HER2) negative cancer
Male participants must agree to use contraception during the intervention period and for at least 95 days after the last dose of chemotherapy, refrain from donating sperm and be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent or must agree to use contraception per study protocol unless confirmed to be azoospermic during this period
Female participants who are not pregnant, not breastfeeding, and at least one of the following conditions applies: not a woman of childbearing potential (WOCBP) OR is a WOCBP who agrees to use contraception or be abstinent from heterosexual intercourse as their preferred and usual lifestyle during the treatment period and for at least 180 days after the last dose of chemotherapy or for at least 120 days after the last dose of pembrolizumab, whichever is last, and agrees not to donate eggs to others or freeze/store for her own use for the purpose of reproduction during this period
Has measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator assessment
Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
Has provided tumor tissue sample deemed adequate for PD-L1 biomarker analysis
Has provided tumor tissue sample for microsatellite instability (MSI) biomarker analysis
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 3 days prior to the start of study intervention
Has adequate organ function as demonstrated by laboratory testing within 10 days prior to the start of study treatment

Exclusion Criteria

Has squamous cell or undifferentiated gastric cancer
Has had major surgery, open biopsy, or significant traumatic injury within 28 days prior to randomization, anticipation of the need for major surgery during the course of study intervention, or has not recovered adequately from the toxicity and/or complications from previous surgery
Has preexisting peripheral neuropathy >Grade 1
Is a WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization or treatment allocation
Has had previous therapy for locally advanced, unresectable or metastatic gastric/GEJ cancer. Participants may have received prior neoadjuvant and/or adjuvant therapy as long as it was completed ≥6 months prior to randomization
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 coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX- 40, CD137)
Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization or has not recovered from all AEs due to any previous therapies to ≤Grade 1 or baseline
Has received prior radiotherapy within 2 weeks prior to study start or has not recovered from all previous radiation-related toxicities, required corticosteroids, and have not had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to noncentral nervous system (CNS) disease
Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study treatment
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
Has a known additional malignancy that is progressing or has required active treatment within the past 5 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
Has known active CNS metastases and/or carcinomatous meningitis
Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
Has an active autoimmune disease that has required systemic treatment in past 2 years
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
Has an active infection requiring systemic therapy
Has a known history of human immunodeficiency virus (HIV) infection
Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as Hepatitis C virus [HCV] ribonucleic acid [RNA] detected qualitatively) infection
Has a known history of active tuberculosis
Has hypokalemia (serum potassium less than the lower limit of normal)
Has hypomagnesemia (serum magnesium less than the lower limit of normal)
Has hypocalcemia (serum calcium less than the lower limit of normal)
Has a history or current evidence of any condition (eg, known deficiency of the enzyme dihydropyrimidine dehydrogenase), therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is last
Has had an allogenic tissue/solid organ transplant
Has a known severe hypersensitivity (≥ Grade 3) to any of the study chemotherapy agents (including, but not limited to, infusional 5-fluorouracil or oral capecitabine) and/or to any of their excipients
For participants taking cisplatin: has Grade ≥2 audiometric hearing loss

ID	Term
D013274	Stomach Neoplasms
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body

ID	Term
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D013272	Stomach Diseases

ID	Term
C582435	pembrolizumab
D002945	Cisplatin
D005472	Fluorouracil
D000077150	Oxaliplatin
D000069287	Capecitabine

ID	Term
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds
D014498	Uracil
D011744	Pyrimidinones
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D056831	Coordination Complexes
D009930	Organic Chemicals
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D003853	Deoxyribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides