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Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants With Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-585/KEYNOTE-585)

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ClinicalTrials.gov Identifier: NCT03221426
Recruitment Status : Recruiting
First Posted : July 18, 2017
Last Update Posted : May 17, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE July 17, 2017
First Posted Date  ICMJE July 18, 2017
Last Update Posted Date May 17, 2019
Actual Study Start Date  ICMJE October 9, 2017
Estimated Primary Completion Date July 26, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 18, 2018)
  • Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]
    OS is defined as the time from randomization to death due to any cause.
  • Event-free Survival (EFS) [ Time Frame: Up to approximately 2 years ]
    EFS is defined as the time from randomization to the first of the following events: radiographic disease progression per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1); local or distant recurrence as assessed by computer tomography (CT) scan or biopsy if indicated (for participants who are disease free after surgery); or death due to any cause. A second primary malignancy is not considered as an EFS event.
  • Pathological Complete Response (pathCR) Rate [ Time Frame: Up to 6 weeks after completion of 3 cycles of neoadjuvant treatment (Up to 15 weeks) ]
    PathCR rate is defined as the percentage of participants having pathCR. pathCR is defined as no invasive disease within an entirely submitted and evaluated gross lesion, and histologically negative nodes.
  • Adverse Events (AEs) [ Time Frame: Up to approximately 27 months ]
    An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE will be presented.
  • Study Treatment Discontinuations Due to AEs [ Time Frame: Up to approximately 2 years ]
    An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented.
Original Primary Outcome Measures  ICMJE
 (submitted: July 17, 2017)
  • Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]
    OS is defined as the time from randomization to death due to any cause.
  • Event-free Survival (EFS) [ Time Frame: Up to approximately 2 years ]
    EFS is defined as the time from randomization to the first of the following events: radiographic disease progression per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1); local or distant recurrence as assessed by computer tomography (CT) scan or biopsy if indicated (for participants who are disease free after surgery); or death due to any cause. A second primary malignancy is not considered as an EFS event.
  • Pathological Complete Response (pathCR) Rate [ Time Frame: Up to 6 weeks after completion of 3 cycles of neoadjuvant treatment (Up to 15 weeks) ]
    PathCR rate is defined as the percentage of participants having pathCR. pathCR is defined as no invasive disease within an entirely submitted and evaluated gross lesion, and histologically negative nodes.
Change History Complete list of historical versions of study NCT03221426 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 27, 2017)
Disease-free Survival (DFS) [ Time Frame: Up to approximately 2 years ]
DFS is defined as the time from post-surgery baseline scan until the first occurrence of local/distant recurrence or death from any cause and is based on RECIST 1.1 as assessed by blinded independent central review.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2017)
Disease-free Survival (DFS) [ Time Frame: Up to approximately 2 years ]
DFS is defined as the time from post-surgery baseline scan until the first occurrence of local/distant recurrence or death from any cause.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants With Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-585/KEYNOTE-585)
Official Title  ICMJE A Phase III, Randomized, Double-Blind, Clinical Trial of Pembrolizumab (MK-3475) Plus Chemotherapy (XP or FP) Versus Placebo Plus Chemotherapy (XP or FP) as Neoadjuvant/Adjuvant Treatment for Subjects With Gastric and Gastroesophageal Junction (GEJ) Adenocarcinoma (KEYNOTE-585)
Brief Summary

The purpose of this study is to evaluate the efficacy of pembrolizumab (MK-3745) in the neoadjuvant (prior to surgery) or adjuvant (after surgery) treatment of previously untreated adults with gastric and gastroesophageal junction (GEJ) adenocarcinoma.

The primary hypotheses of this study are that pembrolizumab plus chemotherapy is superior to placebo plus chemotherapy in terms of overall survival (OS), event-free survival (EFS) and pathological complete response (pathCR) rate.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double-blind study
Primary Purpose: Treatment
Condition  ICMJE
  • Gastric Cancer
  • Gastroesophageal Junction Cancer
Intervention  ICMJE
  • Biological: Pembrolizumab
    IV infusion
    Other Name: MK-3475
  • Drug: Placebo
    Normal saline solution IV infusion
    Other Name: Normal saline solution
  • Drug: Cisplatin
    IV infusion
    Other Name: PLATINOL®
  • Drug: Capecitabine
    Oral tablets
    Other Name: XELODA®
  • Drug: 5-fluorouracil
    IV infusion
    Other Names:
    • ADRUCIL®
    • 5FU
  • Drug: Docetaxel
    IV infusion
    Other Name: TAXOTERE®
  • Drug: Oxaliplatin
    IV infusion
    Other Name: ELOXATIN®
  • Drug: Leucovorin
    IV infusion
    Other Name: WELLCOVORIN®
Study Arms  ICMJE
  • Experimental: Pembrolizumab+Chemotherapy

    Neoadjuvant: Prior to surgery, participants receive 3 cycles of pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets twice each day (BID) on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5-fluorouracil (5FU) via continuous IV infusion on Days 1 to 5 of each 3-week cycle.

    Adjuvant: 4 to 10 weeks post-surgery, participants receive pembrolizumab 200 mg via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5FU via continuous IV infusion on Days 1 to 5 of each 3-week cycle for up to 14 cycles.

    Interventions:
    • Biological: Pembrolizumab
    • Drug: Cisplatin
    • Drug: Capecitabine
    • Drug: 5-fluorouracil
  • Placebo Comparator: Placebo+Chemotherapy

    Neoadjuvant: Prior to surgery, participants receive 3 cycles of placebo (normal saline solution) via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5FU via continuous IV infusion on Days 1 to 5 of each 3-week cycle.

    Adjuvant: 4 to 10 weeks post-surgery, participants receive placebo via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5FU via continuous IV infusion on Days 1 to 5 of each 3-week cycle for up to 14 cycles.

    Interventions:
    • Drug: Placebo
    • Drug: Cisplatin
    • Drug: Capecitabine
    • Drug: 5-fluorouracil
  • Experimental: Pembrolizumab+FLOT Safety Cohort

    FLOT=docetaxel+oxaliplatin+5FU+leucovorin (calcium folinate). Neoadjuvant: Prior to surgery, participants receive 3 cycles of pembrolizumab 200 mg via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m^2 via IV infusion, oxaliplatin 85 mg/m^2 via IV infusion, 5FU 2600 mg/m^2 via IV infusion, and leucovorin (calcium folinate) 200 mg/m^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3) for 4 administrations.

    Adjuvant: 4 to 10 weeks postsurgery, participants receive pembrolizumab 200 mg via IV infusion Day 1 Q3W for up to 11 cycles PLUS docetaxel 50 mg/m^2, oxaliplatin 85 mg/m^2, 5FU 2600 mg/m^2, and leucovorin 200 mg/m^2 Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3) for 4 administrations.

    Interventions:
    • Biological: Pembrolizumab
    • Drug: 5-fluorouracil
    • Drug: Docetaxel
    • Drug: Oxaliplatin
    • Drug: Leucovorin
  • Placebo Comparator: Placebo+FLOT Safety Cohort

    Neoadjuvant: Prior to surgery, participants receive 3 cycles of placebo (normal saline solution) via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m^2 via IV infusion, oxaliplatin 85 mg/m^2 via IV infusion, 5FU 2600 mg/m^2 via IV infusion, and leucovorin 200 mg/m^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3) for 4 administrations.

    Adjuvant: 4 to 10 weeks postsurgery, participants receive placebo via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m^2 via IV infusion, oxaliplatin 85 mg/m^2 via IV infusion, 5FU 2600 mg/m^2 via IV infusion, and leucovorin 200 mg/m^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3) for 4 administrations.

    Interventions:
    • Drug: Placebo
    • Drug: 5-fluorouracil
    • Drug: Docetaxel
    • Drug: Oxaliplatin
    • Drug: Leucovorin
Publications * Bang YJ, Van Cutsem E, Fuchs CS, Ohtsu A, Tabernero J, Ilson DH, Hyung WJ, Strong VE, Goetze TO, Yoshikawa T, Tang LH, Hwang PMT, Webb N, Adelberg D, Shitara K. KEYNOTE-585: Phase III study of perioperative chemotherapy with or without pembrolizumab for gastric cancer. Future Oncol. 2019 Mar;15(9):943-952. doi: 10.2217/fon-2018-0581. Epub 2019 Feb 19.

*   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 18, 2018)
860
Original Estimated Enrollment  ICMJE
 (submitted: July 17, 2017)
800
Estimated Study Completion Date  ICMJE July 26, 2023
Estimated Primary Completion Date July 26, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has previously untreated localized gastric or GEJ adenocarcinoma as defined by T3 or greater primary lesion or the presence of any positive nodes - N+ (clinical nodes) without evidence of metastatic disease.
  • Plans to proceed to surgery following pre-operative chemotherapy based on standard staging studies per local practice.
  • Is willing to provide tissue from a tumor lesion at baseline and at time of surgery.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 within 3 days prior to the first dose of study treatment.
  • Has adequate organ function.
  • Male participants of childbearing potential must agree to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy.
  • Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.
  • Has life expectancy of greater than 6 months.

Exclusion Criteria:

  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
  • Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], tumor necrosis factor receptor superfamily member 4 [OX-40], necrosis factor receptor superfamily member 9 [CD137]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial.
  • Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior the first dose of study treatment.
  • Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are not excluded.
  • Has a known severe hypersensitivity (≥ Grade 3) to pembrolizumab, its active substance and/or any of its excipients, or to any of the study chemotherapy agents and/or to any of their excipients.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years.
  • Has a known history of human immunodeficiency virus (HIV) infection.
  • Has a known history of Hepatitis B or known active Hepatitis C virus infection.
  • Has a known history of active tuberculosis (TB).
  • Female participants who are pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.
  • Male participants who are expecting to father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of chemotherapy.
  • Has had an allogenic tissue/solid organ transplant.
  • Has received a live vaccine within 30 days prior to the first dose of study treatment.
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 Belgium,   Brazil,   Canada,   Chile,   France,   Germany,   Israel,   Italy,   Japan,   Korea, Republic of,   Poland,   Russian Federation,   Singapore,   Taiwan,   United Kingdom,   United States
Removed Location Countries Australia,   Colombia,   Guatemala,   Hong Kong,   Hungary,   Malaysia,   New Zealand,   Philippines,   Spain,   Ukraine
 
Administrative Information
NCT Number  ICMJE NCT03221426
Other Study ID Numbers  ICMJE 3475-585
2016-004408-76 ( EudraCT Number )
MK-3475-585 ( Other Identifier: Merck Protocol Number )
173786 ( Registry Identifier: JAPIC )
KEYNOTE-585 ( Other Identifier: Merck )
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 May 2019

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