First-line Esophageal Carcinoma Study with Chemo vs. Chemo + Pembrolizumab
- Conditions
- locally advanced unresectable or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the esophagogastric junction
- Registration Number
- JPRN-jRCT2080223683
- Lead Sponsor
- MSD K.K.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 700
Have 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 EGJ.
- Have measurable disease per RECIST 1.1 as determined by the local site investigator/radiology assessment.
- Have an ECOG performance status of 0 to 1.
- Provide either a newly obtained or archival tissue sample for PD-L1 by immunohistochemistry analysis.
- Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to randomization.
Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in the protocol, starting with the first dose of study therapy through 120 days after the last dose of study medication and up to 180 days after last dose of cisplatin.
- Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in the protocol, starting with the first dose of study therapy through 120 days after the last dose of study medication and up to 180 days after last dose of cisplatin and refrain from donating sperm during this period.
- Have adequate organ function.
- 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 (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
- 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 trial 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.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of study medication.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (i.e., CTLA-4, OX-40, CD137) 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).
- Has known history of or is positive for hepatitis B (hepatitis B surface antigen reactive) or hepatitis C (hepatitis C virus RNA or hepatitis C antibody is detected).
- Has received a live vaccine within 30 days prior to the first dose of trial drug.
- Has had radiotherapy within 14 days of randomization. Subjects who received radiotherapy >14 days prior to randomization must have completely recovered from any radiotherapy-related AEs/toxicities.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method (1) OS in subjects with esophageal squamous cell carcinoma (ESCC) whose tumors are PD-L1 biomarker positive (CPS >=10)<br>(2) OS in subjects with ESCC<br>(3) OS in subjects whose tumors are PD-L1 biomarker positive (CPS >=10)<br>(4) OS in all subjects<br>(5) PFS per RECIST 1.1, as determined by investigator, in subjects with ESCC<br>(6) PFS per RECIST 1.1, as determined by investigator, in subjects whose tumors are PD-L1 biomarker positive (CPS >=10)<br>(7) PFS per RECIST 1.1, as determined by investigator, in all subjects
- Secondary Outcome Measures
Name Time Method (1) ORR per RECIST 1.1, as determined by investigator, in all subjects<br>(2) ORR per RECIST 1.1, as determined by investigator, in subjects with ESCC whose tumors are PD-L1 biomarker-positive (CPS >=10), in subjects with ESCC, and in subjects whose tumors are PD-L1 biomarker-positive (CPS >=10)<br>(3) DOR per RECIST 1.1, as determined by investigator, in all subjects, in subjects with ESCC whose tumors are PD-L1 biomarker-positive (CPS >=10), in subjects with ESCC, and in subjects whose tumors are PD-L1 biomarker-positive (CPS >=10)<br>(4) Safety and tolerability<br>(5) Changes from baseline in health-related quality of life using the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC Quality Of Life Questionnaire Oesophageal Module (QLQ OES18) in all subjects, in subjects with ESCC whose tumors are PD-L1 biomarker-positive (CPS >=10), in subjects with ESCC, and in subjects whose tumors are PD-L1 biomarker-positive (CPS >=10)