{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:39:00Z","timestamp":1790804340268,"version":"4.1.0"},"reference-count":42,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"6","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Inhibition of WEE1, a tyrosine kinase responsible for G2 arrest, results in premature mitotic entry and double-strand DNA breaks. Adavosertib is a selective, ATP-competitive, and small-molecule WEE1 kinase inhibitor. In an adavosertib single-agent, Phase I trial, partial responses (PRs) were observed in patients with solid tumors carrying pathogenic variants (PVs) in\n                      <jats:italic toggle=\"yes\">BRCA1\/2<\/jats:italic>\n                      . In this trial, we further evaluated adavosertib in patients with PV in\n                      <jats:italic toggle=\"yes\">BRCA1\/2<\/jats:italic>\n                      solid tumors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>\n                      Eligible patients met criteria for the National Cancer Institute-Molecular Analysis for Therapy Choice master protocol and had a diagnosis of advanced\n                      <jats:italic toggle=\"yes\">BRCA-<\/jats:italic>\n                      mutated solid tumor (germline or somatic mutations were accepted); 33 patients were enrolled, and 30 received study treatment. Adavosertib was administered orally, 300 mg once daily, with 5 days on and 2 days off over a 3 week cycle of 2 weeks on and 1 week off, until disease progression or unacceptable toxicity. Radiologic assessment was performed every three cycles. The primary end point was overall response rate (ORR); secondary end points included 6-month overall survival (OS6) and 6-month progression-free survival rate (PFS6).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The ORR was 3.3% (90% CI, 0.2 to 14.9); the OS6 was 57.3% (90% CI, 41.9 to 72.7); the PFS6 was 23.4% (90% CI, 10.7 to 36.2). One PR (fallopian tube serous carcinoma) and six cases of stable disease (SD, &gt;6 months) were observed. In patients with SD &lt;6 months or progressive disease (nonresponders), significantly increased PI3K\/AKT\/mTOR signaling pathway gene transcripts suggested activation of this resistance mechanism. The primary reason for treatment discontinuation was disease progression. Common side effects included myelosuppression, fatigue, nausea, anemia, vomiting, and diarrhea.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      In heavily pretreated, advanced solid tumor patients with PV in\n                      <jats:italic toggle=\"yes\">BRCA1\/2<\/jats:italic>\n                      , adavosertib treatment resulted in low ORR, and this trial did not meet the primary end point.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-00769","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T19:59:13Z","timestamp":1781726353000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Phase II Study of Adavosertib in Patients With Tumors Containing BRCA1 and BRCA2 Mutations: Results From the NCI-MATCH ECOG-ACRIN Cancer Research Group (EAY131) Subprotocol Z1I"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6906-1627","authenticated-orcid":true,"given":"Shivaani","family":"Kummar","sequence":"first","affiliation":[{"name":"Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Heath &amp; Science University School of Medicine, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihe","family":"Song","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute\u2014ECOG-ACRIN Biostatistics Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0774-9914","authenticated-orcid":true,"given":"Kim A.","family":"Reiss","sequence":"additional","affiliation":[{"name":"Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2513-7025","authenticated-orcid":true,"given":"James M.","family":"Ford","sequence":"additional","affiliation":[{"name":"Division of Oncology, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7973-5912","authenticated-orcid":true,"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Frederick National Laboratory for Cancer Research, Frederick, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7080-4352","authenticated-orcid":true,"given":"Annah S.","family":"Rolig","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Heath &amp; Science University School of Medicine, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4455-8789","authenticated-orcid":true,"given":"James A.","family":"Zwiebel","sequence":"additional","affiliation":[{"name":"Investigational Drug Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D.","family":"Gore","sequence":"additional","affiliation":[{"name":"Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5724-4917","authenticated-orcid":true,"given":"Robert J.","family":"Gray","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute\u2014ECOG-ACRIN Biostatistics Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Wang","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute\u2014ECOG-ACRIN Biostatistics Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8195-3206","authenticated-orcid":true,"given":"Lisa M.","family":"McShane","sequence":"additional","affiliation":[{"name":"Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9720-9737","authenticated-orcid":true,"given":"Larry V.","family":"Rubinstein","sequence":"additional","affiliation":[{"name":"Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3855-0166","authenticated-orcid":true,"given":"David","family":"Patton","sequence":"additional","affiliation":[{"name":"Center for Biomedical Informatics &amp; Information Technology, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4245-1155","authenticated-orcid":true,"given":"Jacob","family":"Gross","sequence":"additional","affiliation":[{"name":"Center for Biomedical Informatics &amp; Information Technology, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6250-4210","authenticated-orcid":true,"given":"Donna","family":"Brunnquell","sequence":"additional","affiliation":[{"name":"Center for Biomedical Informatics &amp; Information Technology, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0949-978X","authenticated-orcid":true,"given":"Latifa F.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Center for Biomedical Informatics &amp; Information Technology, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3975-8516","authenticated-orcid":true,"given":"P. Mickey","family":"Williams","sequence":"additional","affiliation":[{"name":"Frederick National Laboratory for Cancer Research, Frederick, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8331-1052","authenticated-orcid":true,"given":"Stanley R.","family":"Hamilton","sequence":"additional","affiliation":[{"name":"City of Hope National Medical Center and Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5790-4954","authenticated-orcid":false,"given":"Naoko","family":"Takebe","sequence":"additional","affiliation":[{"name":"Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8080-7960","authenticated-orcid":true,"given":"Adam","family":"Brufsky","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James V.","family":"Tricoli","sequence":"additional","affiliation":[{"name":"Treatment and Diagnosis, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1445-1684","authenticated-orcid":true,"given":"Barbara A.","family":"Conley","sequence":"additional","affiliation":[{"name":"Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos L.","family":"Arteaga","sequence":"additional","affiliation":[{"name":"UT Southwestern Simmons Comprehensive Cancer Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndsay N.","family":"Harris","sequence":"additional","affiliation":[{"name":"Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9302-4073","authenticated-orcid":true,"given":"Peter J.","family":"O'Dwyer","sequence":"additional","affiliation":[{"name":"Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2919-4326","authenticated-orcid":true,"given":"Alice P.","family":"Chen","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Clinic, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3402-0478","authenticated-orcid":true,"given":"Keith T.","family":"Flaherty","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_9_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00959-2"},{"key":"e_1_3_9_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr697"},{"key":"e_1_3_9_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00412-12"},{"key":"e_1_3_9_5_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-11-0320"},{"key":"e_1_3_9_6_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-09-0463"},{"key":"e_1_3_9_7_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-2580"},{"key":"e_1_3_9_8_2","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.9.7.11115"},{"key":"e_1_3_9_9_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.67.5991"},{"key":"e_1_3_9_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-3796"},{"key":"e_1_3_9_11_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.67.5942"},{"key":"e_1_3_9_12_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-0219"},{"key":"e_1_3_9_13_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.00730"},{"key":"e_1_3_9_14_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.60.4009"},{"key":"e_1_3_9_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djz245"},{"key":"e_1_3_9_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2016.10.007"},{"key":"e_1_3_9_17_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-1597"},{"key":"e_1_3_9_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_3_9_19_2","volume-title":"National Cancer Institute","author":"NIH","unstructured":"NIH: National Cancer Institute. https:\/\/portal.gdc.cancer.gov\/projects\/MATCH-Z1I"},{"key":"e_1_3_9_20_2","volume-title":"High Performance Computing at the NIH","author":"BIOWULF","unstructured":"BIOWULF: High Performance Computing at the NIH. http:\/\/hpc.nih.gov"},{"key":"e_1_3_9_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2514"},{"key":"e_1_3_9_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3036"},{"key":"e_1_3_9_23_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-23-0467"},{"key":"e_1_3_9_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu479"},{"key":"e_1_3_9_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12477"},{"key":"e_1_3_9_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0893-4"},{"key":"e_1_3_9_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-018-0066-6"},{"key":"e_1_3_9_28_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-24-2639"},{"key":"e_1_3_9_29_2","volume-title":"Genomic Characterization CS-MATCH-0007 Arm Z1I","author":"dbGaP","unstructured":"dbGaP: Genomic Characterization CS-MATCH-0007 Arm Z1I. https:\/\/www.ncbi.nlm.nih.gov\/projects\/gap\/cgi-bin\/study.cgi?study_id=phs002058"},{"key":"e_1_3_9_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"e_1_3_9_31_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-1284"},{"key":"e_1_3_9_32_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-0329"},{"key":"e_1_3_9_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-023-01371-6"},{"key":"e_1_3_9_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-023-00965-7"},{"key":"e_1_3_9_35_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.03167"},{"key":"e_1_3_9_36_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.00830"},{"key":"e_1_3_9_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.33048"},{"key":"e_1_3_9_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-08324-2"},{"key":"e_1_3_9_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1382-1"},{"key":"e_1_3_9_40_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.57894"},{"key":"e_1_3_9_41_2","first-page":"908","article-title":"mTOR inhibition overcomes primary and acquired resistance to Wee1 inhibition by augmenting replication stress in epithelial ovarian cancers","volume":"10","author":"Li F","year":"2020","unstructured":"Li F, Guo E, Huang J, et al: mTOR inhibition overcomes primary and acquired resistance to Wee1 inhibition by augmenting replication stress in epithelial ovarian cancers. Am J Cancer Res 10:908-924, 2020","journal-title":"Am J Cancer Res"},{"key":"e_1_3_9_42_2","first-page":"326","article-title":"14-3-3sigma, the double-edged sword of human cancers","volume":"1","author":"Li Z","year":"2009","unstructured":"Li Z, Liu JY, Zhang JT: 14-3-3sigma, the double-edged sword of human cancers. Am J Transl Res 1:326-340, 2009","journal-title":"Am J Transl Res"},{"key":"e_1_3_9_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/44188"}],"container-title":["JCO Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/PO-25-00769","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T19:59:17Z","timestamp":1781726357000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/PO-25-00769"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1200\/PO-25-00769"],"URL":"https:\/\/doi.org\/10.1200\/po-25-00769","relation":{},"ISSN":["2473-4284"],"issn-type":[{"value":"2473-4284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2025-08-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-16","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2500769"}}