{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:01:44Z","timestamp":1790910104723,"version":"4.1.0"},"reference-count":23,"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":[[2024,12]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>\n              The NCI-MATCH trial assigned patients with solid tumors, lymphomas, or multiple myeloma to targeted therapies on the basis of identified genetic alterations from tumor biopsies. In preclinical models,\n              <jats:italic>neurofibromatosis 2<\/jats:italic>\n              (\n              <jats:italic>NF2<\/jats:italic>\n              )\u2013inactivated tumors display sensitivity to focal adhesion kinase (FAK) inhibition. The EAY131-U subprotocol evaluated the efficacy of defactinib, a FAK inhibitor, in patients with\n              <jats:italic>NF2<\/jats:italic>\n              -altered tumors.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>\n              Patients whose tumors harbored an inactivating\n              <jats:italic>NF2<\/jats:italic>\n              mutation on next-generation sequencing were assigned to subprotocol U. Defactinib 400 mg was given orally twice a day until progression or intolerable toxicity. The primary end point was objective response rate (ORR), secondary end points included toxicity, progression-free survival (PFS), and 6-month PFS.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              Of 5,548 patients with sufficient tissue for genomic analysis, 57 patients were found to have\n              <jats:italic>NF2<\/jats:italic>\n              alterations. Thirty-five patients ultimately enrolled and 33 were treated, with one not having central confirmation and two ineligible for outcome analysis. All patients had received previous treatment, with 52% having received three or more previous lines of therapy. The most common treatment-related toxicities were fatigue (36%), nausea (33%), and hyperbilirubinemia (27%), with 27% of patients having grade 3 toxicities. Median follow-up was 35.9 months with an ORR of 3% from one partial response in a patient with choroid meningioma. Among the 12 patients (40%) with a best response of stable disease, eight demonstrated some tumor shrinkage. Median PFS was 1.9 months, and six patients achieved a PFS &gt;5.5 months. No correlation was identified between clinical outcomes and tumor histology or specific\n              <jats:italic>NF2<\/jats:italic>\n              genotype.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>\n              This protocol did not meet its prespecified primary end point. Defactinib monotherapy had limited clinical activity in this cohort of previously treated patients with solid tumors exhibiting\n              <jats:italic>NF2<\/jats:italic>\n              loss.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/po.24.00327","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T20:59:16Z","timestamp":1734555556000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":8,"title":["Phase II Study of Defactinib (VS6063) in Patients With Tumors With\n            <i>NF2<\/i>\n            Loss: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol U"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6109-5790","authenticated-orcid":true,"given":"Marjorie G.","family":"Zauderer","sequence":"first","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY and Westchester Medical Center and New York Medical College, Valhalla, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1763-8214","authenticated-orcid":true,"given":"Opeyemi","family":"Jegede","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute-ECOG-ACRIN Biostatistics Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Jackman","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute, Boston, MA"}],"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5724-4917","authenticated-orcid":true,"given":"Robert J.","family":"Gray","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute-ECOG-ACRIN Biostatistics Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Wang","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute-ECOG-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 R.","family":"Patton","sequence":"additional","affiliation":[{"name":"Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5790-4954","authenticated-orcid":true,"given":"Naoko","family":"Takebe","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\/0000-0001-7661-797X","authenticated-orcid":true,"given":"Raymond","family":"Huang","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3336-0336","authenticated-orcid":true,"given":"Jose A.","family":"Carrillo","sequence":"additional","affiliation":[{"name":"University of California, Irvine, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3985-253X","authenticated-orcid":true,"given":"Andrew J.","family":"Brenner","sequence":"additional","affiliation":[{"name":"University of Texas Health Sciences Center, San Antonio, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3975-8516","authenticated-orcid":true,"given":"James V.","family":"Tricoli","sequence":"additional","affiliation":[{"name":"Division of Cancer 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":"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9774-6719","authenticated-orcid":true,"given":"Lyndsay N.","family":"Harris","sequence":"additional","affiliation":[{"name":"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":"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 Cancer Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-0456"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1213"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209587"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-015-0282-y"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2017.1416937"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23476"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv123"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-01009-7"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.23273"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-0151"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4694"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv193"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2016.10.007"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-1597"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djab115"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.54.8800"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.26.3541"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30206-6"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2018.04.034"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdh059"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02371"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.79.0543"}],"container-title":["JCO Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/PO.24.00327","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T20:59:18Z","timestamp":1734555558000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/PO.24.00327"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":23,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1200\/PO.24.00327"],"URL":"https:\/\/doi.org\/10.1200\/po.24.00327","relation":{},"ISSN":["2473-4284"],"issn-type":[{"value":"2473-4284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12]]},"assertion":[{"value":"2024-06-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-23","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2400327"}}