A Clinical Trial of Ifinatamab Deruxtecan in People With Advanced Esophageal Cancer (MK-3475-06F)

The purpose of this trial is to assess if ifinatamab deruxtecan (I-DXd) can treat esophageal squamous cell carcinoma (ESCC). I-DXd is an antibody-drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. The goal of this trial is to learn how many participants who receive I-DXd have the cancer respond, which means the cancer gets smaller or goes away.

The master screening protocol is MK-3475-U06 (KEYMAKER-U06)

Inclusion Criteria: * Has a histologically or cytologically confirmed diagnosis of unresectable locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) * Has disease progression after 1 or 2 prior lines of systemic therapy for unresectable locally advanced or metastatic ESCC * Has measurable disease * If infected with human immunodeficiency virus (HIV), has well-controlled HIV on antiretroviral therapy * Has adequate organ function Exclusion Criteria: * Has histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma subtype * Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention * Has clinically significant corneal disease * Has any of the following within 6 months before screening: cerebrovascular accident, transient ischemic attack, other arterial thromboembolic event * If infected with HIV, has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Has uncontrolled or significant cardiovascular disease * Has a known additional malignancy that is progressing or has required active treatment within the past 3 years * Has known active central nervous system metastases and/or carcinomatous meningitis * Has a history of (noninfectious) pneumonitis/interstitial lung disease irrespective of requiring steroids or has any current pneumonitis/interstitial lung disease or has suspected pneumonitis/interstitial lung disease * Has active infection requiring systemic therapy other than those permitted. * Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc), and potential pulmonary involvement caused by any autoimmune, connective tissue, or inflammatory disorders (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc), prior pneumonectomy, or requirement for supplemental oxygen