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Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-859/KEYNOTE-859)

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ClinicalTrials.gov Identifier: NCT03675737
Recruitment Status : Recruiting
First Posted : September 18, 2018
Last Update Posted : April 5, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE September 17, 2018
First Posted Date  ICMJE September 18, 2018
Last Update Posted Date April 5, 2021
Actual Study Start Date  ICMJE November 8, 2018
Estimated Primary Completion Date September 28, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 22, 2021)
Overall Survival (OS) [ Time Frame: Up to approximately 54 months ]
OS is the time from randomization to death due to any cause.
Original Primary Outcome Measures  ICMJE
 (submitted: September 17, 2018)
  • Overall Survival (OS) [ Time Frame: Up to approximately 24 months ]
    OS is the time from randomization to death due to any cause.
  • Progression-free Survival (PFS) [ Time Frame: Up to approximately 24 months ]
    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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2021)
  • Progression-free Survival (PFS) [ Time Frame: Up to approximately 54 months ]
    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).
  • Objective Response Rate (ORR) [ Time Frame: Up to approximately 54 months ]
    ORR was defined as the percentage of participants who have a confirmed 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, taking as reference the baseline sum diameters) per RECIST 1.1 as assessed by BICR.
  • Duration of Response (DOR) [ Time Frame: Up to approximately 54 months ]
    DOR is determined by disease assessment and is defined as the time from first response (CR or PR) to disease progression, or death from any cause, whichever occurs first.
  • Percentage of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to approximately 54 months ]
    Percentage of participants experiencing an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment.
  • Percentage of Participants Discontinuing Study Drug Due to AEs [ Time Frame: Up to approximately 54 months ]
    Percentage of participants discontinuing study treatment due to an AE.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2018)
  • Objective Response Rate (ORR) [ Time Frame: Up to approximately 24 months ]
    ORR was defined as the percentage of participants who have a confirmed 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, taking as reference the baseline sum diameters) per RECIST 1.1 as assessed by BICR.
  • Duration of Response (DOR) [ Time Frame: Up to approximately 24 months ]
    DOR is determined by disease assessment and is defined as the time from first response (CR or PR) to disease progression, or death from any cause, whichever occurs first.
  • Percentage of Participants Experiencing Adverse Events (AEs) [ Time Frame: From time of signing informed consent form (ICF) until the end of follow-up (up to approximately 27 months) ]
    Percentage of participants experiencing an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment
  • Percentage of Participants Discontinuing Study Drug Due to AEs [ Time Frame: From time of signing ICF until the end of study treatment (up to approximately 24 months) ]
    Percentage of participants discontinuing study treatment due to an AE
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-859/KEYNOTE-859)
Official Title  ICMJE A Phase 3, Randomized, Double-blind Clinical Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy as First-line Treatment in Participants With HER2 Negative, Previously Untreated, Unresectable or Metastatic Gastric Orgastroesophageal Junction Adenocarcinoma (KEYNOTE-859)
Brief Summary

The purpose of this study is to evaluate the efficacy of pembrolizumab (MK-3745) in combination with chemotherapy (Cisplatin combined with 5-Fluorouracil [FP regimen] or oxaliplatin combined with capecitabine [CAPOX regimen]) versus placebo in combination with chemotherapy (FP or CAPOX regimens) in the treatment of human epidermal growth factor receptor 2 (HER2) negative advanced gastric or GEJ adenocarcinoma in adult participants.

The primary hypotheses of this study are that pembrolizumab plus chemotherapy is superior to placebo plus chemotherapy in terms of overall survival (OS).

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Stomach Neoplasms
Intervention  ICMJE
  • Biological: Pembrolizumab
    Administered as an IV infusion on Day 1 Q3W
    Other Names:
    • KEYTRUDA®
    • MK-3475
  • Drug: Cisplatin
    Administered as an IV infusion on Day 1 Q3W
    Other Name: PLATINOL®
  • Drug: 5-fluorouracil
    Administered as a continuous IV infusion on Days 1-5 Q3W
    Other Names:
    • ADRUCIL®
    • 5FU
  • Drug: oxaliplatin
    Administered as an IV infusion on Day 1 Q3W
    Other Name: ELOXATIN®
  • Drug: capecitabine
    Administered orally BID on Days 1 to 14 Q3W
    Other Name: XELODA®
  • Drug: Placebo for Pembrolizumab
    Administered as an IV infusion on Day 1 Q3W
Study Arms  ICMJE
  • Experimental: Pembrolizumab + FP or CAPOX
    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).
    Interventions:
    • Biological: Pembrolizumab
    • Drug: Cisplatin
    • Drug: 5-fluorouracil
    • Drug: oxaliplatin
    • Drug: capecitabine
  • Active Comparator: Placebo + FP or CAPOX
    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.
    Interventions:
    • Drug: Cisplatin
    • Drug: 5-fluorouracil
    • Drug: oxaliplatin
    • Drug: capecitabine
    • Drug: Placebo for Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 7, 2020)
1542
Original Estimated Enrollment  ICMJE
 (submitted: September 17, 2018)
780
Estimated Study Completion Date  ICMJE September 28, 2024
Estimated Primary Completion Date September 28, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 treatment period and through 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 through 180 days after the last dose of chemotherapy or through 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 co-inhibitory 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 non central 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Listed Location Countries  ICMJE Argentina,   Australia,   Brazil,   Canada,   Chile,   China,   Colombia,   Costa Rica,   Czechia,   Denmark,   France,   Germany,   Guatemala,   Hong Kong,   Hungary,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   New Zealand,   Peru,   Poland,   Russian Federation,   South Africa,   Spain,   Switzerland,   Taiwan,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03675737
Other Study ID Numbers  ICMJE 3475-859
2018-001757-27 ( EudraCT Number )
MK-3475-859 ( Other Identifier: Merck Protocol Number )
KEYNOTE-859 ( Other Identifier: Merck )
JAPIC-CTI ( Registry Identifier: 194649 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP