Study of Pembrolizumab (MK-3475) Versus Placebo in Participants With Esophageal Carcinoma Who Are Receiving Chemotherapy and Radiation Therapy (MK-3475-975/KEYNOTE-975)

  • STATUS
    Recruiting
  • End date
    Feb 21, 2026
  • participants needed
    600
  • sponsor
    Merck Sharp & Dohme Corp.
Updated on 27 October 2021
Investigator
Toll Free Number
Primary Contact
Hospital Nacional Arzobispo Loayza ( Site 0143) (0.8 mi away) Contact
+155 other location
carcinoma
squamous cell carcinoma
oxaliplatin
chemoradiotherapy
pembrolizumab
leucovorin
chemotherapy regimen
esophageal carcinoma
adenocarcinoma
mk-3475
ebrt
external radiation

Summary

The purpose of this study is to assess the efficacy and safety of treatment with definitive chemoradiotherapy (dCRT) + pembrolizumab (MK-3475) compared to treatment with dCRT + placebo with respect to Overall Survival (OS) and Event-free Survival (EFS) in:

  • participants with esophageal squamous cell carcinoma (ESCC),
  • participants whose tumors express Programmed Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) 10, and
  • all participants.

The primary study hypotheses are that dCRT+ pembrolizumab is better than dCRT + placebo with respect to:

  • OS in participants with ESCC,
  • OS in participants whose tumors express PD-L1 CPS 10,
  • OS in all participants,
  • EFS in participants with ESCC,
  • EFS in participants whose tumors express PD-L1 CPS 10, and
  • EFS in all participants.

Description

Participants receive pembrolizumab or placebo PLUS one of two chemotherapy regimens PLUS radiation therapy for up to approximately one year. The chemotherapy regimens are either:

  • FP (5-fluorouracil [5-FU] + cisplatin) or
  • FOLFOX (5-FU + oxaliplatin + leucovorin or levoleucovorin).

Details
Condition Esophageal Cancer, Squamous cell carcinoma, Esophageal Adenocarcinoma, Esophageal Squamous Cell Carcinoma, Squamous Cell Carcinoma of Esophagus, Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), Siewert Type I Adenocarcinoma of the Esophagogastric Junction (EGJ), adenocarcinoma of esophagus, Gastroesophageal Junction Carcinoma (GEJC), Gastroesophageal Junction Carcinoma (GEJC), Gastroesophageal Junction Carcinoma (GEJC), Gastroesophageal Junction Carcinoma (GEJC), Gastroesophageal Junction Carcinoma (GEJC), Gastroesophageal Junction Carcinoma (GEJC), Gastroesophageal Junction Carcinoma (GEJC), Gastroesophageal Junction Carcinoma (GEJC), Gastroesophageal Junction Carcinoma
Treatment cisplatin, Radiotherapy, Placebo, Pembrolizumab, Oxaliplatin, 5-FU, Leucovorin, Levoleucovorin
Clinical Study IdentifierNCT04210115
SponsorMerck Sharp & Dohme Corp.
Last Modified on27 October 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Has histologically or cytologically confirmed diagnosis of CTX N+ M0 or cT2-T4a NX M0 ESCC, GEJC, EAC, or histologically or cytologically confirmed diagnosis of cTX N+ M1 cervical or upper thoracic esophageal carcinoma with supraclavicular lymph node metastases only
Is deemed suitable for dCRT
Is ineligible for curative surgery based on the documented opinion of a qualified medical/surgical/radiation oncologist
Is not expected to require tumor resection during the course of the study
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days of the first dose of study treatment
Has adequate organ function
Male participants must use adequate contraception (a male condom plus partner use of an additional contraceptive method) unless confirmed to be azoospermic (vasectomized or secondary to medical cause) and refrain from donating sperm during the study treatment period and through 90 days after the last dose of chemotherapy
Female participants who are a Woman of Childbearing Potential (WOCBP) must use contraception that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle, during the study treatment period through 180 days after the last dose of chemotherapy or 120 days after the last dose of pembrolizumab, whichever is greater, and agree not to donate eggs to others or freeze/store for her own use for the purpose of reproduction during this period
Female participants must not be pregnant or breastfeeding

Exclusion Criteria

Has direct invasion of tumor into adjacent organs such as the aorta or trachea or has radiographic evidence of >90 degree encasement or invasion of a major blood vessel, or of intratumoral cavitation
Has had major surgery other than for insertion of a feeding tube, open biopsy, or significant traumatic injury within 28 days prior to randomization, or anticipates the need for major surgery during study treatment; participants with gastric or esophageal fistulae are excluded
Has had weight loss of >20% in the previous 3 months
Has had prior chemotherapy or radiotherapy for esophageal cancer
Has had a myocardial infarction within the past 6 months
Has symptomatic congestive heart failure
Has received prior therapy with an anti-programmed cell death-1 (anti PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention; administration of killed vaccines is allowed
Has received any prior systemic anticancer therapy for esophageal cancer including investigational agents
Has not recovered from all adverse events (AEs) due to previous non-anticancer therapies to Grade 1 or Baseline
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded from the study. Participants with localized prostate cancer that has undergone potentially curative treatment can be enrolled in the study
Has severe hypersensitivity (Grade 3) to pembrolizumab, any of the study chemotherapy agents, or their 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 or known active Hepatitis C virus infection
Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
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 treatment (180 days for participants receiving cisplatin who are breastfeeding)
Has had an allogenic tissue/solid organ transplant
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