A Phase III Randomized Open-Label Study of Single Agent Pembrolizumab vs. Physicians' Choice of Single Agent Docetaxel, Paclitaxel, or Irinotecan in Subjects with Advanced/Metastatic Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus that have Progressed after First-Line Standard Therapy (KEYNOTE-181)
- Conditions
- gulletcancer10017934
- Registration Number
- NL-OMON45950
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
Subjects must: ;1. Be * 18 years of age on the day of signing the informed consent. ;2. Have histologically or cytologically confirmed diagnosis of adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the EGJ. ;3. Have metastatic disease or locally advanced, unresectable disease. ;4. Have a life expectancy greater than 3 months. ;5. Have measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment. ;6. Have an ECOG performance status of 0 or 1. ;7. Have experienced documented radiographic or clinical disease progression on one previous line of standard therapy. ;8. Provide either a newly obtained or archival tissue sample for intratumoral immune-related GEP analysis.;9. Demonstrate adequate organ function. ;10. Negative pregnancy test for females of child bearing potential prior to starting study and male and female subjects of childbearing potential must be willing to use an adequate method of contraception.
The subject will be excluded from participating in the trial if the subject:
1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of treatment. ;2. Has an active autoimmune disease that has required systemic treatment in past 2 years. ;3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. ;4. Has known central nervous system (CNS) metastases and/or carcinomatous meningitis (includes past history or current metastasis). ;5. Has received prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., * Grade 1 or at baseline) from adverse events due to a previously administered agent. The specified 2-week period between last dose of prior therapy and first dose of pembrolizumab is the minimum amount of time required. Subjects may not receive study medication less than 2 weeks from the last dose of a prior therapy. However, a period of more than 2 weeks may be used if
indicated both clinically and due to concern between possible negative interactions
between prior therapy and study therapy.;6. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or if the subject has previously participated in Merck pembrolizumab (MK-3475) clinical trials. ;7. Previously had a severe hypersensitivity reaction to treatment with another
monoclonal antibody (mAb);8. Has experienced documented objective radiographic or clinical disease progression during or after receiving more than 1 line of therapy.;9. Has a diagnosed additional malignancy within 5 years prior to treatment allocation with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cervical and/or breast cancers. ;10. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject*s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.;11. Has a known history of Human Immunodeficiency Virus (HIV) infection. ;12. Has untreated known active Hepatitis B or known Hepatitis C. ;13. Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis;14. Has an active infection requiring systemic therapy. ;15. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. ;16. 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 pembrolizumab or through 180 days after the last dose of paclitaxel, docetaxel or irinotecan.;17. Has a Known allergy, hypersensitivity, or contraindication to preselected
chemotherapy agent (i.e. paclitaxel, docetaxel, or irinotecan) or any components used
in their preparation. ;18. Experienced weight loss > 10% over approximately 2 months prior to first dose of study therapy.;19. Has clinically apparent ascites or pleural eff
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>1. Overall Survival (OS) in subjects with squamous cell carcinoma of the<br /><br>Esophagus.<br /><br>2. Overall Survival (OS) in subjects with PD-L1 CPS*10%<br /><br>3. Overall Survival (OS) in all subjects.</p><br>
- Secondary Outcome Measures
Name Time Method <p>1.Progression-free survival (PFS) * RECIST 1.1 by central imaging<br /><br>vendor review in all subjects, defined as the time from randomization to<br /><br>the first documented disease progression per RECIST 1.1 or death.<br /><br>2.Objective Response Rate (ORR) * RECIST 1.1 by central imaging<br /><br>vendor review in all subjects, defined as the proportion of the subjects in<br /><br>the analysis population who have a complete response (CR) or partial<br /><br>response (PR).<br /><br>3. Safety and tolerability Endpoints</p><br>