Safety and pharmacokinetics (PK) of lurbinectedin (lurbi) in pediatric patients (pts) with relapsed/refractory (R/R) solid tumors and preliminary antitumor activity in pediatric and young adult pts with R/R Ewing sarcoma (EwS): Results from a phase 1 study.

11518 Background: About 30% of pediatric cancers are solid tumors. EwS is the second most common bone tumor among children and young adults; 5-year survival rates for R/R EwS are <15%. Lurbi is a trabectedin analogue that alkylates DNA and blocks transcription of EWS-FLI1, a primary driver of EwS. In a phase 2 basket trial, lurbi demonstrated an objective response rate (ORR; complete response CR or partial response PR) of 14% and disease control rate (DCR; CR, PR, or stable disease) of 57% in 28 adults (median age, 33 years y) with R/R EwS. Here, we report phase 1 results from a multicenter, open-label study (NCT05734066) of lurbi in pediatric and young adult pts with R/R solid tumors including EwS. Methods: Part 1 evaluated the safety, tolerability, PK, and recommended phase 2 dose (RP2D) of lurbi monotherapy in pediatric pts (aged 2–18 y) with R/R solid tumors. RP2D selection used a Bayesian optimal interval design starting with the approved adult dosage, 3.2 mg/m 2 lurbi IV over 1 hour every 3 weeks. Two additional cohorts were treated at the RP2D: a safety cohort for pts aged <18 y and a histology-specific safety and efficacy cohort for pts aged 2–30 y with R/R EwS. Tumor responses were assessed every 6 weeks per RECIST v1.1. Results: As of Oct 22, 2025, 21 pts received ≥1 dose of lurbi (3.2 mg/m 2 , n = 17; 4.0 mg/m 2 , n = 4). Median (range) age was 16 (10–25) y; 13 (62%) pts had received ≥3 prior lines of treatment (Tx). Median (range) lurbi cycles administered was 3 (1–18); 3 (14%) pts were still receiving lurbi; 18 (86%) discontinued Tx. At 4 mg/m 2 , dose-limiting pulmonary edema and rhabdomyolysis/acute kidney injury were observed. Among pts receiving lurbi 3.2 mg/m², 8 (47%) had grade ≥3 Tx-related adverse events (TRAEs); anemia (5 29%) and platelet count decrease (5 29%) were most common (Table). For pts aged ≥6 y, the RP2D was 3.2 mg/m 2 ; accrual of pts aged <6 y is ongoing to determine RP2D. Although geometric mean (Geo CV%) C max (163 µg/L 105%) and AUC inf (1893 µg∙h/L 126%) were higher in children/young adults vs adults in the phase 2 basket trial (increased 53% and 244%, respectively), there was substantial overlap in drug exposures. Among 11 evaluable pts with R/R EwS receiving lurbi 3.2 mg/m², the confirmed ORR was 18%, and the DCR was 55%; 2 responders were progression free at their last assessments (5.7 and 6.9 months). Conclusions: Based on these data, lurbi had a manageable safety profile, predictable PK properties, and encouraging preliminary clinical activity in pts with R/R EwS. Phase 2 expansion in pts ≤30 y with R/R EwS is ongoing. Clinical trial information: NCT05734066 . TRAEs in all pts and by dose. n (%) All N = 21 3.2 mg/m 2 n = 17 4.0 mg/m 2 n = 4 Any TRAE 21 (100) 17 (100) 4 (100) Grade ≥3 12 (57) 8 (47) 4 (100) Serious 4 (19) 2 (12) 2 (50) Led to Tx discontinuation 1 (5) 0 1 (25) Led to death 1 (5) 0 1 (25) a a Due to acute kidney injury.