Abstract
SARC037: Phase II results of trabectedin given as a 1-hour (h) infusion in combination with low dose irinotecan in patients (pts) with relapsed/refractory Ewing sarcoma (ES)
Journal of clinical oncology, Vol.42(16_suppl), pp.11508-11508
06/01/2024
DOI: 10.1200/JCO.2024.42.16_suppl.11508
Abstract
11508 Background: Trabectedin(T) is a marine-derived minor groove DNA binding compound that alters transcription factor activity. Preclinical data suggests that T suppresses the oncogenic driver of ES, EWS::FLI1. This suppression requires a threshold concentration of T and is potentiated by low doses of Irinotecan(I). Preliminary clinical activity and reversal of the EWS::FLI1 transcriptome was seen in patients (pts) in the phase I portion of SARC037. Here we report the phase II results of T with I at the recommended dose in pts with relapsed/refractory ES. Methods: In this open-label multicenter study, T was given at 1 mg/m 2 as a 1-h infusion on day(D)1 with I at 25 mg/m 2 intravenously on D2 and D4 of a 21D cycle. Key eligibility criteria were EWS::FLI1 fusion transcript, age ≥6 years, ECOG ≤2, adequate organ function, and willing to have a research biopsy if safely accessible. The primary objective was to determine the objective response rate (ORR) assessed by RECIST v1.1. Secondary objectives were progression-free survival (PFS), duration of response (DOR), and safety. This study used a Simon two-stage design that required 4 or more responses (CR or PR) at the final analysis to establish treatment activity. Results: 18 pts enrolled from 12/2022-12/2023 across 6 sites, 8F/10M, median age 21y (9-43). Pts had a median of 3 (1-7) prior therapy lines, including I in 67% of pts. Of 16 pts evaluable for response at the cutoff date, 5 pts had a PR, and 2 pts had SD. Two pts have evaluations pending and two pts were removed for toxicity before the first evaluation. Median time to response was 2.6 months(m), 6-month PFS was 37.7% (95% CI 18.3%, 77.7%), and all responses were sustained at the time of data cutoff at 10.4+, 7.5+, 5.5+, 5.0+ and 4.6+ m. There were no G5 AEs. Most pts had molecular profiling, translocation testing, as well as ctDNA collection, quantitation, and analysis. A subset of pts had pre- and post-treatment biopsies for RNA sequencing and evaluation of the impact of drug exposure on the EWS::FLI1 transcriptome. Conclusions: T+I exhibited anti-tumor activity in heavily pretreated pts with ES and met its prespecified ORR with 5 PRs in 16 evaluable patients, all of which are ongoing at data cutoff. There were no unexpected safety signals. The combination of T given as a 1h infusion and low-dose I demonstrated meaningful clinical benefit and is worthy of further study in ES pts. Analysis of biological correlates is ongoing. Clinical trial information: NCT04067115 .
Details
- Title: Subtitle
- SARC037: Phase II results of trabectedin given as a 1-hour (h) infusion in combination with low dose irinotecan in patients (pts) with relapsed/refractory Ewing sarcoma (ES)
- Creators
- Patrick Joseph Grohar - Children's Hospital of PhiladelphiaKarla V. Ballman - Mayo Clinic in ArizonaRachel Heise - Cornell UniversityLeo Mascarenhas - Children's Hospital of Los AngelesJohn Glod - National Institutes of Health Clinical CenterMary Frances Frances Wedekind - National Institutes of HealthJenna Marie Gedminas - University of IowaSteven G. DuBois - Dana-Farber Cancer InstituteRobert G. Maki - Memorial Sloan Kettering Cancer CenterBrian D. Crompton - Dana-Farber Cancer InstituteWilliam Douglas Figg - National Cancer InstituteRochelle Bagatell - Children's Hospital of PhiladelphiaTheodore Willis Laetsch - Children's Hospital of PhiladelphiaMark Diamond - University of PennsylvaniaFariba Navid - Children's Hospital of Los AngelesRyan David Roberts - Nationwide Children's HospitalBrigitte C. Widemann - National Cancer InstituteDenise K. Reinke - University of Michigan–Ann ArborRashmi Chugh - Michigan Medicine
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.42(16_suppl), pp.11508-11508
- DOI
- 10.1200/JCO.2024.42.16_suppl.11508
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Language
- English
- Date published
- 06/01/2024
- Academic Unit
- Stead Family Department of Pediatrics; Hematology/Oncology
- Record Identifier
- 9984649055702771
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