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A Study to Evaluate Investigational Agents With or Without Pembrolizumab (MK-3475) in Participants With Advanced Esophageal Cancer Previously Exposed to Programmed Cell Death 1 Protein (PD-1)/ Programmed Cell Death Ligand 1 (PD-L1) Treatment (MK-3475-06B)

Phase 1
Recruiting
Conditions
Esophageal Squamous Cell Carcinoma
Registration Number
NCT05319730
Lead Sponsor
Merck Sharp & Dohme LLC
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
All
Target Recruitment
Not specified
Inclusion Criteria

The main inclusion and exclusion criteria include but are not limited to the following:<br><br>Inclusion Criteria:<br><br> - Histologically or cytologically confirmed diagnosis of metastatic or locally<br> advanced unresectable ESCC.<br><br> - Has experienced investigator documented radiographic or clinical disease progression<br> on one prior line of standard therapy, that includes a platinum agent and previous<br> exposure to an anti-PD1/PD-L1 based therapy.<br><br> - Has an evaluable baseline tumor sample (newly obtained or archival) for analysis.<br><br> - Has adequately controlled blood pressure (BP) with or without antihypertensive<br> medications.<br><br> - Participants who have adverse events (AEs) due to previous anticancer therapies must<br> have recovered to =Grade 1 or baseline. Participants with endocrine-related AEs who<br> are adequately treated with hormone replacement or participants who have =Grade 2<br> neuropathy are eligible.<br><br>Exclusion Criteria:<br><br> - Direct invasion into adjacent organs such as the aorta or trachea.<br><br> - Has experienced weight loss >10% over approximately 2 months prior to first dose of<br> study therapy.<br><br> - Has history of documented severe dry eye syndrome, severe Meibomian gland disease<br> and/or blepharitis, or corneal disease that prevents/delays corneal healing.<br><br> - Has active inflammatory bowel disease requiring immunosuppressive medication or<br> previous history of inflammatory bowel disease.<br><br> - Currently participating in or has participated in a study of an investigational<br> agent or has used an investigational device within 4 weeks before the first dose of<br> study intervention.<br><br> - Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or<br> any other form of immunosuppressive therapy within 7 days prior to the first dose of<br> study medication.<br><br> - Known additional malignancy that is progressing or has required active treatment<br> within the past 3 years, except basal cell carcinoma of the skin, squamous cell<br> carcinoma of the skin, or carcinoma in situ that has undergone potentially curative<br> therapy.<br><br> - Known active central nervous system (CNS) metastases and/or carcinomatous<br> meningitis.<br><br> - Active autoimmune disease that has required systemic treatment in past 2 years.<br><br> - History of human immunodeficiency virus (HIV) infection.<br><br> - History of Hepatitis B or known active Hepatitis C virus infection.<br><br> - History of allogenic tissue/solid organ transplant.<br><br> - Clinically significant cardiovascular disease within 12 months from first dose of<br> study intervention.<br><br> - Known GI malabsorption or any other condition that may affect the absorption of<br> lenvatinib. (Not applicable to actively enrolling arms as of Amendment 5)<br><br> - Has risk for significant GI bleeding such as a serious nonhealing wound, peptic<br> ulcer, or bone fracture within 28 days prior to allocation/randomization,<br> significant bleeding disorders, vasculitis, or has had a significant bleeding<br> episode from the GI tract within 12 weeks prior to allocation/randomization. (Not<br> applicable to actively enrolling arms as of Amendment 5)

Exclusion Criteria

Not provided

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) During Safety Lead-in Phase;Number of Participants Experiencing Adverse Events (AEs) During Safety Lead-in Phase;Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase;Objective Response Rate (ORR)
Secondary Outcome Measures
NameTimeMethod
Progression-Free Survival (PFS);Duration of Response (DOR);Overall Survival (OS);Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase;Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase
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