First-line Esophageal Carcinoma Study With Chemo vs. Chemo Plus Pembrolizumab (MK-3475-590/KEYNOTE-590)-China Extension Study
Esophageal Neoplasms
About this trial
This is an interventional treatment trial for Esophageal Neoplasms focused on measuring Programmed Cell Death-1 (PD-1), Programmed Cell Death 1 (PD1), Programmed Cell Death-Ligand 1 (PD-L1, PDL1), Programmed Cell Death-Ligand 2 (PD-L2, PDL2)
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- Anhui Provincial Hospital ( Site 0106)
- The First Affiliated Hospital of Anhui Medical University ( Site 0112)
- Peking Union Medical College Hospital ( Site 0123)
- The First Affiliated Hospital of Xiamen University ( Site 0119)
- Guangdong General Hospital ( Site 0103)
- The Affiliated Tumour Hospital of Harbin Medical University ( Site 0102)
- Hunan Cancer Hospital ( Site 0105)
- PLA Cancer Centre of Nanjing Bayi Hospital ( Site 0110)
- Jiangsu Cancer Hospital ( Site 0117)
- Zhongda Hospital Southeast University ( Site 0125)
- Jilin Cancer Hospital ( Site 0101)
- The First Affiliated Hospital of Xi an Jiaotong University ( Site 0120)
- Zhejiang Cancer Hospital ( Site 0116)
- Beijing Cancer Hospital ( Site 0100)
- Fujian Provincial Cancer Hospital ( Site 0104)
- Shanghai Chest Hospital ( Site 0111)
- Fudan University Shanghai Cancer Center ( Site 0108)
- Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0114)
- Tongji Medical College Huazhong University of Science and Technology ( Site 0109)
- Henan Cancer Hospital ( Site 0107)
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Pembrolizumab + Cisplatin + 5-FU
Placebo + Cisplatin + 5-FU
Participants receive pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W), cisplatin 80 mg/m^2 IV Q3W, and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours). All treatments will be administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants receive placebo to pembrolizumab (saline) IV Q3W, cisplatin 80 mg/m^2 IV Q3W, and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours). All treatments will be administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.