{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:11:47Z","timestamp":1792069907416,"version":"4.4.0"},"reference-count":48,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO Oncology Advances"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>We hypothesized that ACR-368 (prexasertib) would be active in desmoplastic small round cell tumor (DSRCT) because of favorable responses in preclinical models.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>Preclinical work identified ACR-368 activity in DSRCT, and a phase I\/II trial of ACR-368 and irinotecan in patients 12 months and older with relapsed\/refractory DSRCT was conducted. The primary objectives were determination of recommended phase II dose (RP2D) and best overall response rate (ORR) at the RP2D in DSRCT, with \u22653 of 16 responses considered promising.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>Preclinical data confirmed ACR-368 as potentially therapeutic in DSRCT, and 19 patients were enrolled in a subsequent clinical trial. Treatment was well tolerated, and cytopenias were managed using growth factors. Fifteen of 19 patients, including five of six achieving PR, had previously received irinotecan. The estimated ORR at the RP2D was 23% (lower boundary one-sided 90% CI, 9%), exceeding the unpromising rate of 5%. In addition, three patients with DSRCT had a PR at doses other than the RP2D, bringing the ORR for all doses (n = 19) to 32% (90% CI, 15% to 53%). The median overall survival was 19 months (95% CI, 13 to 36).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>\n              The RP2D of ACR-368 with irinotecan by age group is ACR-368 105 or 150 mg\/m\n              <jats:sup>2<\/jats:sup>\n              once on day 1 (&gt;21 years or \u226421 years, respectively) and irinotecan 15 mg\/m\n              <jats:sup>2<\/jats:sup>\n              once daily for 5 days in 21-day cycles for both groups. The study met its primary objective to consider ACR-368 and irinotecan promising in DSRCT and, to our knowledge, is the first incorporating a targeted therapy to achieve this magnitude of response.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/oa-24-00095","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T15:59:10Z","timestamp":1745855950000},"source":"Crossref","is-referenced-by-count":5,"title":["ACR-368, a CHK1\/2 Kinase Inhibitor, in Patients With Relapsed or Refractory Desmoplastic Small Round Cell Tumor: Phase I\/II Trial Results"],"prefix":"10.1200","clinical-trial-number":[{"clinical-trial-number":"nct04095221","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4463-5759","authenticated-orcid":true,"given":"Emily K.","family":"Slotkin","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, 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