First-line Esophageal Carcinoma Study With Pembrolizumab Plus Chemo vs. Chemo (MK-3475-590/KEYNOTE-590)

Completed · Phase 3 · Has a placebo group

Conditions studied: Esophageal Neoplasms

In brief

The purpose of this trial is to evaluate efficacy and safety of pembrolizumab plus standard of care (SOC) chemotherapy with cisplatin and 5-fluorouracil (5-FU) versus placebo plus SOC chemotherapy with cisplatin and 5-FU as first-line treatment in participants with locally advanced or metastatic esophageal carcinoma. The overall primary efficacy hypotheses are as follows: 1. In participants with esophageal squamous cell carcinoma (ESCC), participants whose tumors are programmed cell death-ligand 1 (PD-L1)-positive (defined as combined positive score \[CPS\] ≥10), ESCC participants whose tumors are PD-L1 positive (CPS ≥10), and in all participants, overall survival (OS) is superior with pembrolizumab plus SOC chemotherapy compared with placebo plus SOC chemotherapy. 2. In participants with ESCC, participants whose tumors are PD-L1 positive (CPS ≥10), and in all participants, progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by investigator is superior with pembrolizumab plus SOC chemotherapy compared with placebo plus SOC chemotherapy.

Key facts

Study ID: NCT03189719
Run by: Merck Sharp & Dohme LLC
People needed: 749
Starts: 2017-07-25
Expected to finish: 2023-07-10
Last updated by the study team: 2024-10-15

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the esophagogastric junction (EGJ)
Has measurable disease per RECIST 1.1 as determined by the local site investigator/radiology assessment
Eastern Cooperative Group (ECOG) performance status of 0 to 1
Can provide either a newly obtained or archival tissue sample for PD-L1 by immunohistochemistry analysis
Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to randomization and be willing to use an adequate method of contraception (e.g. abstinence, intrauterine device, diaphragm with spermicide, etc.) for the course of the study through 120 days after the last dose of study treatment and up to 180 days after last dose of cisplatin
Male participants of childbearing potential must agree to use an adequate method of contraception (e.g. abstinence, vasectomy, male condom, etc.) starting with the first dose of study treatment through 120 days after the last dose of study treatment and up to 180 days after last dose of cisplatin, and refrain from donating sperm during this period
Has adequate organ function

You may not qualify if…

Has locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy (as determined by local investigator)
Has had previous therapy for advanced/metastatic adenocarcinoma or squamous cell cancer of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the EGJ
Has had 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
Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ breast cancer that has undergone potentially curative therapy, and in situ or intramucosal pharyngeal cancer
Has known active central nervous system metastases and/or carcinomatous meningitis.
Has an active autoimmune disease that has required systemic treatment in past 2 years
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 7 days prior to the first dose of study treatment, or has a history of organ transplant, including allogeneic stem cell transplant
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis, or has an active infection requiring systemic therapy
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study medication and up to 180 days after last dose of cisplatin
Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in a pembrolizumab (MK-3475) clinical trial
Has severe hypersensitivity (≥ Grade 3) to any study treatment (pembrolizumab, cisplatin, or 5-FU) and/or any of its excipients
Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis) or human immunodeficiency virus (HIV) infection
Has known history of or is positive for hepatitis B or hepatitis C
Has received a live vaccine within 30 days prior to the first dose of study treatment
Has had radiotherapy within 14 days of randomization. Participants who received radiotherapy >14 days prior to randomization must have completely recovered from any radiotherapy-related AEs/toxicities

Where it is running

The University of Chicago Medical Center ( Site 0001) — Chicago, Illinois, United States
University of Kansas ( Site 0029) — Westwood, Kansas, United States
University of Maryland Medical Center ( Site 0013) — Baltimore, Maryland, United States
Dana Farber Cancer Center ( Site 0009) — Boston, Massachusetts, United States
Henry Ford Cancer Center ( Site 0018) — Detroit, Michigan, United States
Washington University School of Medicine ( Site 0031) — St Louis, Missouri, United States
Roswell Park Cancer Institute ( Site 0004) — Buffalo, New York, United States
Weill Cornell Medical College ( Site 0024) — New York, New York, United States
University Hospitals Cleveland Medical Center ( Site 0002) — Cleveland, Ohio, United States
UPMC Cancer Center/Hillman Cancer Center ( Site 0015) — Pittsburgh, Pennsylvania, United States
University of Tennessee Medical Center Knoxville ( Site 0017) — Knoxville, Tennessee, United States
Centro de Investigaciones Clinicas - Clinica Viedma ( Site 0603) — Viedma, Río Negro Province, Argentina
Hospital Aleman ( Site 0605) — Buenos Aires, Argentina
Hospital Municipal de Gastroenterologia Dr. Bonorino Udaondo ( Site 0602) — Buenos Aires, Argentina
Sanatorio Allende - Cordoba ( Site 0604) — Córdoba, Argentina
Hospital Privado Centro Medico Cordoba ( Site 0601) — Córdoba, Argentina
Blacktown Hospital ( Site 2000) — Blacktown, New South Wales, Australia
Liverpool Hospital. ( Site 2001) — Liverpool, New South Wales, Australia
Princess Alexandra Hospital ( Site 2005) — Woolloongabba, Queensland, Australia
Eastern Health ( Site 2002) — Box Hill, Victoria, Australia
Peter MacCallum Cancer Centre ( Site 2003) — Melbourne, Victoria, Australia
CETUS Hospital Dia Oncologia ( Site 0208) — Belo Horizonte, Minas Gerais, Brazil
Inst de Medicina Integral Professor Fernando Figueira- IMIP ( Site 0210) — Recife, Pernambuco, Brazil
Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0209) — Rio de Janeiro, Rio de Janeiro, Brazil
Kaiser Permanente Southern California ( Site 0003) — West Los Angeles, California, United States

Full record on ClinicalTrials.gov

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