Clinical Trials /

Study of Pembrolizumab (MK-3475) as First-Line Monotherapy and Combination Therapy for Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (MK-3475-062/KEYNOTE-062)

NCT02494583

Description:

This is a study of pembrolizumab (MK-3475) as first-line treatment for participants with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. Participants will be randomly assigned to one of the three treatment arms of the study: pembrolizumab as monotherapy, or pembrolizumab + cisplatin + 5-fluorouracil (5-FU) or capecitabine, or placebo + cisplatin + 5-FU or capecitabine. The primary study hypotheses are that pembrolizumab in combination with chemotherapy is superior to chemotherapy alone in terms of Progression-free Survival (PFS) and Overall Survival (OS) in participants with programmed death-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 and that pembrolizumab combination with chemotherapy is superior to chemotherapy alone in terms of OS in participants with PD-L1 CPS ≥10. Primary study hypotheses also are that pembrolizumab monotherapy non-inferior to chemotherapy alone in terms of OS in participants PD-L1 CPS ≥1 and is superior to chemotherapy alone in terms of OS in participants with PD-L1 CPS ≥1 and in participants with PD-L1 CPS ≥10.

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

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Study of <span class="go-doc-concept go-doc-intervention">Pembrolizumab (MK-3475)</span> as First-Line Monotherapy and Combination Therapy for Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (<span class="go-doc-concept go-doc-intervention">MK-3475</span>-062/KEYNOTE-062)

Title

  • Brief Title: Study of Pembrolizumab (MK-3475) as First-Line Monotherapy and Combination Therapy for Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (MK-3475-062/KEYNOTE-062)
  • Official Title: A Randomized, Active-Controlled, Partially Blinded, Biomarker Select, Phase III Clinical Trial of Pembrolizumab as Monotherapy and in Combination With Cisplatin+5-Fluorouracil Versus Placebo+Cisplatin+5-Fluorouracil as First-Line Treatment in Subjects With Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
  • Clinical Trial IDs

    NCT ID: NCT02494583

    ORG ID: 3475-062

    NCI ID: 2015-000972-88

    Trial Conditions

    Gastric Adenocarcinoma

    Trial Interventions

    Drug Synonyms Arms
    cisplatin Pembrolizumab + cisplatin + 5-FU, Placebo + cisplatin + 5-FU
    5-FU Pembrolizumab + cisplatin + 5-FU, Placebo + cisplatin + 5-FU
    capecitabine Pembrolizumab + cisplatin + 5-FU, Placebo + cisplatin + 5-FU

    Trial Purpose

    This is a study of pembrolizumab (MK-3475) as first-line treatment for participants with
    advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. Participants will be
    randomly assigned to one of the 3 treatment arms of the study: pembrolizumab as monotherapy,
    or pembrolizumab + cisplatin + 5-fluorouracil (5-FU) or capecitabine, or placebo + cisplatin
    + 5-FU or capecitabine. The primary hypothesis is that pembrolizumab provides a clinically
    meaningful progression free and/or overall survival.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Pembrolizumab monotherapy Experimental Participants receive pembrolizumab 200 mg, intravenously (IV) on Day 1 of each 3 week cycle (Q3W)
    Pembrolizumab + cisplatin + 5-FU Experimental Participants receive pembrolizumab 200 mg Q3W + cisplatin 80 mg/m^2 Q3W + 5-FU 800 mg/m^2/day IV infusion on Days 1-5 Q3W. Capecitabine 1000 mg/m^2 twice a day (BID) on Days 1-14 Q3W may be substituted for 5-FU per local guidelines. cisplatin, 5-FU, capecitabine
    Placebo + cisplatin + 5-FU Active Comparator Participants receive placebo, IV, Q3W + cisplatin 80 mg/m^2 Q3W + 5-FU 800 mg/m^2/day IV infusion on Days 1-5 Q3W. Capecitabine 1000 mg/m^2 BID on Days 1-14 Q3W may be substituted for 5-FU per local guidelines. cisplatin, 5-FU, capecitabine

    Eligibility Criteria

    Inclusion Criteria:

    - Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
    Performance Scale

    - Have histologically- or cytologically-confirmed diagnosis of locally advanced or
    metastatic gastric or GEJ adenocarcinoma

    - HER2/neu protein negative and programmed cell death ligand 1 (PD-L1)-positive

    - Have measurable disease

    - Female participants of childbearing potential should be willing to use 2 methods of
    birth control or be surgically sterile, or abstain from heterosexual activity for the
    course of the trial through 180 days after the last dose of study medication

    - Male participants should agree to use an adequate method of contraception starting
    with the first dose of study medication through 180 days after the last dose of study
    medication

    - Adequate organ function

    Exclusion Criteria:

    - Squamous cell or undifferentiated gastric cancer

    - Previous therapy for locally advanced or metastatic gastric/GEJ cancer. Participant
    may have received prior neoadjuvant or adjuvant therapy as long as it was completed
    at least 6 months prior to randomization

    - Major surgery, open biopsy or significant traumatic injury within 28 days prior to
    randomization, or anticipation of the need for major surgery during the course of
    study treatment.

    - Radiotherapy within 14 days of randomization

    - Known additional malignancy that is progressing or requires active treatment with the
    exception of basal cell carcinoma of the skin, 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

    - Active autoimmune disease that has required systemic treatment in past 2 years

    - Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form
    of immunosuppressive therapy within 7 days prior to the first dose of study
    medication

    - History or evidence of interstitial lung disease or active, non-infectious
    pneumonitis

    - Active infection requiring systemic therapy

    - Pregnant, breastfeeding, or expecting to conceive or father children within the
    projected duration of the trial, starting with the screening visit through 180 days
    after the last dose of study medication

    - Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, or anti-PD-L2
    agent

    - Known history of human immunodeficiency virus (HIV)

    - Known active Hepatitis B or C

    - Currently participating in and receiving study therapy or has participated in a study
    of an investigational agent and received study therapy or used an investigational
    device within 4 weeks prior to the first dose of study medication

    - Received a live vaccine within 30 days of planned start of study medication

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression Free Survival (PFS)

    Overall Survival (OS)

    Secondary Outcome Measures

    Overall Response Rate (ORR)

    Trial Keywords

    Gastric carcinoma

    Gastric cancer

    Gastroesophageal junction cancer

    Gastroesophageal junction carcinoma

    PD1

    PDL1