SARC037: Results of phase I study of trabectedin given as a 1-hour (h) infusion in combination with low dose irinotecan in relapsed/refractory Ewing sarcoma (ES).

• DOI: 10.1200/jco.2023.41.16_suppl.11519
• Publication Date: 2023-06-04T16:31:33Z
• Authors: Patrick Grohar; Karla V. Ballman; Rachel Heise; John Glod; Mary Frances Wede...; Leo Mascarenhas; Jenna Marie Gedminas; Steven G. DuBois; Robert G. Maki; Brian D. Crompton; Masanori Hayashi; Cody J. Peer; William Douglas Figg; Maria Liza Linden...; Esther Mena Gonzalez; Rochelle Bagatell; Theodore Willis L...; Brigitte C. Widemann; Denise K. Reinke; Rashmi Chugh
• Keywords: Refractory (planetary science)

11519 Background: Recurrent ES carries a poor prognosis, and systemic therapies have limited efficacy. Preclinical models suggested that trabectedin (T) could achieve serum concentrations high enough to suppress the dominant oncogene of (i.e. EWS::FLI1 transcription factor), this effect is sustained by subsequent administration low dose irinotecan (I). We conducted phase I study T+I in patients (pts) with ES. Methods: This multicenter escalation employed standard 3+3 design. T was given as 1-h infusion on day (D)1 intravenously D2 4 21D cycle. Dose limiting toxicities (DLTs) were evaluated cycle one. Eligibility required confirmed fusion transcript, age ≥10 years, ECOG performance status ≤2, adequate organ function willing research biopsy if safely accessible. Primary objectives determine recommended (RD) safety T+I. Secondary comprised efficacy avidity for 3'-Deoxy-3'- 18 F Fluorothymidine ( F-FLT) PET. Results: 20 pts enrolled from 1/2021-12/2022 across 5 sites, 5F/15M, median years (range 10-59). Pts had received 2-9) prior therapy lines including 60% pts. Grade (G) 3/4 treatment-emergent adverse events (TEAEs) occurring ≥10% were: elevated ALT/AST, creatinine phosphokinase, febrile neutropenia, anemia, lymphopenia, thrombocytopenia. There 2 G5 respiratory TEAEs. F-FLT PET scans obtained tumors avid. level (DL)2 RD. At DL above, there PRs, 6 SD 14 evaluable (Table). Conclusions: can be administered heavily pretreated ES, demonstrating activity at RD 3 PRs (n=5 evaluable). The may useful understand patterns disease progression Correlative studies will critical understanding mechanism drug activity. Given clinical benefit seen RD, II portion ≥6 old actively accruing. Clinical trial information: NCT04067115 . [Table: see text]