The aim of this study was to determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic profile of E7107 in patients with advanced solid tumors. Patients in this phase I, open-label, single-arm, dose-escalation study had metastatic or locally advanced solid tumors and received E7107 as a 30-minute intravenous infusion at doses of 0.6, 1.2, 1.8, 2.4, 3.2, 4.3, and 5.7 mg/m². Twenty-six patients were enrolled in the study. At 5.7 mg/m², two patients experienced dose-limiting toxicities including diarrhea, vomiting, dehydration, and myocardial infarction on Days 1–3 following E7107 administration. Three additional patients were recruited at the lower dose and all six patients tolerated E7107 4.3 mg/m² with no dose-limiting toxicities. The maximum tolerated dose of E7107 was therefore 4.3 mg/m². The most common drug-related adverse events were nausea, vomiting, and diarrhea. Vision loss was experienced by two patients at Cycles 2 and 7, each patient receiving 3.2 mg/m² and 4.3 mg/m², respectively. This resulted in the study being put on clinical hold. Pharmacokinetic analysis showed that E7107 was rapidly distributed with a moderate elimination half-life (6–13 h) and high clearance. Exposure to E7107 was dose-related. The best tumor response was stable disease in eight patients. E7107 is a unique first-in-class molecule. The incidence of two cases of vision loss probably related to E7107 led to study discontinuation.