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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)

NCT03675737

Description:

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).

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 3475-859
  • SECONDARY ID: 2018-001757-27
  • SECONDARY ID: MK-3475-859
  • SECONDARY ID: KEYNOTE-859
  • SECONDARY ID: JAPIC-CTI
  • NCT ID: NCT03675737

Conditions

  • Stomach Neoplasms

Interventions

DrugSynonymsArms
PembrolizumabKEYTRUDA®, MK-3475Pembrolizumab + FP or CAPOX
CisplatinPLATINOL®Pembrolizumab + FP or CAPOX
5-fluorouracilADRUCIL®, 5FUPembrolizumab + FP or CAPOX
oxaliplatinELOXATIN®Pembrolizumab + FP or CAPOX
capecitabineXELODA®Pembrolizumab + FP or CAPOX
Placebo for PembrolizumabPlacebo + FP or CAPOX

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab + FP or CAPOXExperimentalParticipants 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).
  • Pembrolizumab
  • Cisplatin
  • 5-fluorouracil
  • oxaliplatin
  • capecitabine
Placebo + FP or CAPOXActive ComparatorParticipants 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.
  • Cisplatin
  • 5-fluorouracil
  • oxaliplatin
  • capecitabine
  • Placebo for Pembrolizumab

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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Up to approximately 54 months
Safety Issue:
Description:OS is the time from randomization to death due to any cause.

Secondary Outcome Measures

Measure:Progression-free Survival (PFS)
Time Frame:Up to approximately 54 months
Safety Issue:
Description: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).
Measure:Objective Response Rate (ORR)
Time Frame:Up to approximately 54 months
Safety Issue:
Description: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.
Measure:Duration of Response (DOR)
Time Frame:Up to approximately 54 months
Safety Issue:
Description: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.
Measure:Percentage of Participants Experiencing Adverse Events (AEs)
Time Frame:Up to approximately 54 months
Safety Issue:
Description: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.
Measure:Percentage of Participants Discontinuing Study Drug Due to AEs
Time Frame:Up to approximately 54 months
Safety Issue:
Description:Percentage of participants discontinuing study treatment due to an AE.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • programmed cell death 1 (PD-1, PD1)
  • programmed cell death ligand 1 (PD-L1, PDL1)
  • programmed cell death ligand 2 (PD-L2, PDL2)

Last Updated

April 5, 2021