{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T16:45:26Z","timestamp":1793724326892,"version":"4.6.1"},"reference-count":41,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"10","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Datopotamab deruxtecan (Dato-DXd) is a trophoblast cell-surface antigen-2\u2013directed antibody-drug conjugate with a highly potent topoisomerase I inhibitor payload. The TROPION-Lung05 phase II trial (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT04484142\">NCT04484142<\/jats:ext-link>\n                      ) evaluated the safety and clinical activity of Dato-DXd in patients with advanced\/metastatic non\u2013small cell lung cancer (NSCLC) with actionable genomic alterations progressing on or after targeted therapy and platinum-based chemotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>Patients received Dato-DXd 6 mg\/kg once every 3 weeks. The primary end point was objective response rate (ORR) by blinded independent central review. Secondary end points included duration of response (DOR), safety, tolerability, and survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Among 137 patients who received at least 1 dose of Dato-DXd, 71.5% received at least three lines of prior therapies for advanced\/metastatic disease. Overall, 56.9% had\n                      <jats:italic>EGFR<\/jats:italic>\n                      mutations and 24.8% had\n                      <jats:italic>ALK<\/jats:italic>\n                      rearrangements. Median treatment duration was 4.4 months (range, 0.7-20.6). The confirmed ORR was 35.8% (95% CI, 27.8 to 44.4) overall, and 43.6% (95% CI, 32.4 to 55.3) and 23.5% (95% CI, 10.7 to 41.2) in those with\n                      <jats:italic>EGFR<\/jats:italic>\n                      mutations and\n                      <jats:italic>ALK<\/jats:italic>\n                      rearrangements, respectively. The median DOR was 7.0 months (95% CI, 4.2 to 9.8), and the overall disease control rate was 78.8% (95% CI, 71.0 to 85.3). Grade \u22653 treatment-related adverse events (TRAEs) occurred in 28.5% of patients. The most common TRAE was stomatitis (preferred term; any grade: 56.2%; grade \u22653: 9.5%). Five (3.6%) patients experienced adjudicated treatment-related interstitial lung disease\/pneumonitis, with 1 (0.7%) grade 5 event.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Encouraging and durable antitumor activity was observed with Dato-DXd in this heavily pretreated advanced\/metastatic NSCLC population with actionable genomic alterations. The rate of treatment-related grade \u22653 toxicities was comparable with previous observations, and no new safety signals were observed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-24-01349","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T16:00:15Z","timestamp":1736179215000},"page":"1254-1265","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":136,"title":["Datopotamab Deruxtecan in Advanced or Metastatic Non\u2013Small Cell Lung Cancer With Actionable Genomic Alterations: Results From the Phase II TROPION-Lung05 Study"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct04484142","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4663-7464","authenticated-orcid":true,"given":"Jacob","family":"Sands","sequence":"first","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5740-9654","authenticated-orcid":true,"given":"Myung-Ju","family":"Ahn","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3048-4352","authenticated-orcid":true,"given":"Aaron","family":"Lisberg","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5562-270X","authenticated-orcid":true,"given":"Byoung Chul","family":"Cho","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"George","family":"Blumenschein","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0390-5716","authenticated-orcid":true,"given":"Elaine","family":"Shum","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4478-0523","authenticated-orcid":true,"given":"Elvire","family":"Pons Tostivint","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7437-5054","authenticated-orcid":true,"given":"Yasushi","family":"Goto","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6928-357X","authenticated-orcid":true,"given":"Kiyotaka","family":"Yoh","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital East, Kashiwa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7397-2009","authenticated-orcid":true,"given":"Rebecca","family":"Heist","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Cancer Center, Harvard Medical School, Harvard University, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Aichi Cancer Center Hospital, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Seok","family":"Lee","sequence":"additional","affiliation":[{"name":"Seoul National University Bundang Hospital, Seongnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Baas","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1565-8310","authenticated-orcid":true,"given":"David","family":"Planchard","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3296-423X","authenticated-orcid":true,"given":"Maurice","family":"P\u00e9rol","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7620-0098","authenticated-orcid":true,"given":"Enriqueta","family":"Felip","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu-Chou","family":"Su","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zebger-Gong","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Europe GmbH, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2918-827X","authenticated-orcid":true,"given":"Lan","family":"Lan","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo, Inc, Basking Ridge, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea","family":"Liu","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo, Inc, Basking Ridge, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Howarth","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo, Inc, Basking Ridge, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Chiaverelli","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo, Inc, Basking Ridge, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1947-3364","authenticated-orcid":true,"given":"Luis","family":"Paz-Ares","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_9_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21654"},{"key":"e_1_3_9_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11203200"},{"key":"e_1_3_9_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol30030239"},{"key":"e_1_3_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.12.009"},{"key":"e_1_3_9_6_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12587"},{"key":"e_1_3_9_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.959637"},{"key":"e_1_3_9_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep33658"},{"key":"e_1_3_9_9_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15647"},{"key":"e_1_3_9_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14235936"},{"key":"e_1_3_9_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-21-0206"},{"key":"e_1_3_9_12_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.00059"},{"key":"e_1_3_9_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_3_9_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2024.102720"},{"key":"e_1_3_9_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1913662"},{"key":"e_1_3_9_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1713137"},{"key":"e_1_3_9_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2021.100280"},{"key":"e_1_3_9_18_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.03123"},{"key":"e_1_3_9_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.10.117"},{"key":"e_1_3_9_20_2","unstructured":"Ahn MJ Tanaka K Paz-Ares L et al: Datopotamab deruxtecan versus docetaxel for previously treated advanced or metastatic non\u2013small cell lung cancer: The randomized open-label phase III TROPIONLung01 study. J Clin Oncol 43:260-272 2025"},{"key":"e_1_3_9_21_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.16_suppl.8501"},{"key":"e_1_3_9_22_2","doi-asserted-by":"crossref","unstructured":"Fang W Wang Q Cheng Y et al: Sacituzumab tirumotecan (SKB264\/MK-2870) in combination with KL-A167 (anti-PD-L1) as first-line treatment for patients with advanced NSCLC from the phase II OptiTROP-Lung01 study. Presented at the 2024 ASCO Annual Meeting Chicago IL May 31-June 4 2024","DOI":"10.1200\/JCO.2024.42.16_suppl.8502"},{"key":"e_1_3_9_23_2","doi-asserted-by":"crossref","unstructured":"Paz-Ares LG Juan-Vidal O Mountzios GS et al: Sacituzumab govitecan (SG) vs docetaxel (doc) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC) previously treated with platinum (PT)-based chemotherapy (chemo) and PD(L)-1inhibitors (IO): Primary results from the phase 3 EVOKE-01 study. Presented at the 2024 ASCO Annual Meeting Chicago IL May 31-June 4 2024","DOI":"10.1200\/JCO.2024.42.17_suppl.LBA8500"},{"key":"e_1_3_9_24_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-3563"},{"key":"e_1_3_9_25_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-1123"},{"key":"e_1_3_9_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-021-03784-3"},{"key":"e_1_3_9_27_2","unstructured":"United States Food and Drug Administration: Full prescribing information ENHERTU 2022. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/761139s021lbl.pdf"},{"key":"e_1_3_9_28_2","unstructured":"United States Food and Drug Administration: Full prescribing information: KADCYLA 2023. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2013\/125427lbl.pdf"},{"key":"e_1_3_9_29_2","unstructured":"United States Food and Drug Administration: Highlights of prescribing information: ADCETRIS 2018. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/125388s099lbl.pdf"},{"key":"e_1_3_9_30_2","unstructured":"United States Food and Drug Administration: Full prescribing information: TIVDAK 2021. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/761208Orig1s000lbledt.pdf"},{"key":"e_1_3_9_31_2","unstructured":"United States Food and Drug Administration: Full prescribing information: ELAHERE 2022. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/761310s000lbl.pdf"},{"key":"e_1_3_9_32_2","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol30090582"},{"key":"e_1_3_9_33_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.16_suppl.8623"},{"key":"e_1_3_9_34_2","unstructured":"United States Food and Drug Administration: Highlights of prescribing information: BLENREP 2020. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/761158s000lbl.pdf"},{"key":"e_1_3_9_35_2","unstructured":"United States Food and Drug Administration: Highlights of prescribing information: ENHERTU 2022. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/761139s021lbl.pdf"},{"key":"e_1_3_9_36_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.16_suppl.TPS9146"},{"key":"e_1_3_9_37_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.24.00733"},{"key":"e_1_3_9_38_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.16_suppl.9114"},{"key":"e_1_3_9_39_2","unstructured":"United States Food and Drug Administration: Full prescribing information: TRODELVY 2023. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/761115s035lbl.pdf"},{"key":"e_1_3_9_40_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01476"},{"key":"e_1_3_9_41_2","unstructured":"ClinicalTrials.gov: HERTHENA-Lung02: A study of patritumab deruxtecan versus platinum-based chemotherapy in metastatic or locally advanced EGFRm NSCLC after failure of EGFR TKI therapy 2023. https:\/\/clinicaltrials.gov\/study\/NCT05338970?term=herthena%20lung02&rank=1"},{"key":"e_1_3_9_42_2","article-title":"BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic solid tumor: Results from a first-in-human phase 1 study","volume":"41","author":"Zhang L","year":"2023","unstructured":"Zhang L, Ma Y, Zhao Y, et al: BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic solid tumor: Results from a first-in-human phase 1 study. J Clin Oncol 41, 2023 (suppl 16; abstr 3001)","journal-title":"J Clin Oncol"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO-24-01349","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T18:09:25Z","timestamp":1743185365000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO-24-01349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":41,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1200\/JCO-24-01349"],"URL":"https:\/\/doi.org\/10.1200\/jco-24-01349","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"2024-06-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-05","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}