Background: Eribulin mesylate, a synthetic analog of Halichondrin B, is a novel microtubule dynamics inhibitor. It inhibits microtubule growth without effects on microtubule shortening and promotes nonproductive tubulin aggregate formation. We performed a phase 1 trial to determine the dose limiting toxicities (DLT), maximum tolerated dose (MTD) and pharmacokinetics (PK) of eribulin in children with refractory or recurrent solid tumors, including lymphomas. Methods: Eribulin was administered intravenously on days 1 and 8 in 21-day cycles. Three dose levels (1.1, 1.4 and 1.8 mg/m²/dose) were evaluated using the rolling-6 design with additional patients enrolled into a PK expansion cohort at the MTD/recommended phase 2 dose (RP2D). PK samples were obtained following the Day 1 dose of cycle 1. Results: To date, 23 patients ages 3-17 (median 14) years have been enrolled, with 21 fully evaluable for toxicity. Subjects enrolled with 10 unique tumor types the most common of which were osteosarcoma (n = 9) and Ewing sarcoma (n = 4). During the dose escalation phase, DLTs occurred in 0/6 and 1/6 subjects at 1.1 and 1.4 mg/m²/dose, respectively. At 1.8 mg/m²/dose 2/5 subjects experienced dose-limiting (grade 4) neutropenia. The DLTs, which occurred in a single patient at 1.4 mg/m²/dose, included Grade 4 neutropenia and Grade 3 fatigue. No further DLTs have been observed in the expansion cohort at 1.4 mg/m²/dose. Grade 3/4 non-DLT non-hematologic toxicities across all dose levels and cycles included increases in ALT and AST, anorexia, nausea and hypokalemia. No episodes of ≥ Gr 2 QTc prolongation or peripheral neuropathy were reported. Eribulin exposure was dose-dependent and elimination half-life was ~36hr. Conclusions: Eribulin was well-tolerated in children with refractory/recurrent solid tumors with neutropenia identified as the primary DLT. The RP2D of eribulin mesylate is 1.4 mg/m²/dose on days 1 and 8 of a 21-day cycle. Clinical trial information: NCT02171260