{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T20:29:22Z","timestamp":1787776162257,"version":"build-2784847793"},"reference-count":31,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"8","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Molecular response (MR) based on circulating tumor DNA (ctDNA) is emerging as a promising early biomarker of treatment efficacy in solid tumors; however, its clinical utility in high-grade serous ovarian cancer (HGSOC) remains to be established. This study evaluates the potential predictive value of ctDNA-based MR in with patients HGSOC treated with the WEE1 inhibitor azenosertib.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Plasma cell-free DNA was collected at baseline and after the first and\/or second cycle of treatment from 123 patients with recurrent HGSOC enrolled in clinical trials of azenosertib (N = 123). Using the set samples evaluable by high throughput DNA sequencing, MR was defined as a reduction of\n                      <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                      variant allelic fraction &gt;50% at the earliest evaluable on-treatment time point. MR was compared with radiographic response per Response Evaluation Criteria in Solid Tumors v1.1, time to progression (TTP), and CA-125 dynamics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Molecular responders showed a higher objective response rate (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .012, odds ratio = 0.26), greater tumor shrinkage (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 5.1e-5, Kruskal-Wallis), and a significantly longer TTP than nonresponders (TTP median 5.49 months\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      2.69 months,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 3.8e-5, hazard ratios [HR] = 0.43). MR was able to identify patients with prolonged survival among those having stable disease at the first radiographic assessment (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 3.8e-3, HR = 0.44), and their MR preceded the best overall response by several weeks. Accounting for matching collection time points, MR was evaluable in more patients than CA-125, 88% (102 of 116) versus 71% (85 of 116), respectively, leading to similar predictive value (HR = 0.41\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      0.45, TTP evaluation).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Our findings support the validity and potential clinical utility of ctDNA-based MR as a minimally invasive, rapid, and reliable early surrogate end point in HGSOC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-00844","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:59:06Z","timestamp":1787774346000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Response Assessment From Circulating Tumor DNA in Patients With Ovarian Cancer Treated With the WEE1 Inhibitor Azenosertib"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6616-9245","authenticated-orcid":true,"given":"Jinkil","family":"Jeong","sequence":"first","affiliation":[{"name":"Zentalis Pharmaceuticals, Inc, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9374-2673","authenticated-orcid":true,"given":"Jianhui","family":"Ma","sequence":"additional","affiliation":[{"name":"Zentalis Pharmaceuticals, Inc, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Abed","sequence":"additional","affiliation":[{"name":"Zentalis Pharmaceuticals, Inc, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heekyung","family":"Chung","sequence":"additional","affiliation":[{"name":"Zentalis Pharmaceuticals, Inc, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris","family":"Kim","sequence":"additional","affiliation":[{"name":"Zentalis Pharmaceuticals, Inc, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandini","family":"Molden","sequence":"additional","affiliation":[{"name":"Zentalis Pharmaceuticals, Inc, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Rajendran","sequence":"additional","affiliation":[{"name":"Zentalis Pharmaceuticals, Inc, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhwan","family":"Shim","sequence":"additional","affiliation":[{"name":"Zentalis Pharmaceuticals, Inc, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle D.","family":"Jandial","sequence":"additional","affiliation":[{"name":"Zentalis Pharmaceuticals, Inc, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0840-2368","authenticated-orcid":true,"given":"Fiona","family":"Simpkins","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Penn Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6816-6072","authenticated-orcid":true,"given":"Funda","family":"Meric-Bernstam","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3790-4858","authenticated-orcid":false,"given":"Leslie M.","family":"Randall","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology Clinical Research and Gynecologic Cancer Service Line, Inova Schar Cancer Institute, Inova Health System, Fairfax, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Lackner","sequence":"additional","affiliation":[{"name":"Zentalis Pharmaceuticals, Inc, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8098-9888","authenticated-orcid":true,"given":"Olivier","family":"Harismendy","sequence":"additional","affiliation":[{"name":"Zentalis Pharmaceuticals, Inc, San Diego, 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