{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:02:37Z","timestamp":1784955757946,"version":"3.55.0"},"reference-count":70,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The emergence of antibody-drug conjugates (ADCs) targeting trophoblast cell-surface antigen 2 (TROP2) represents a potential paradigm shift in the treatment of EGFR-mutated non-small cell lung cancer (NSCLC), a setting historically characterized by limited therapeutic options following progression on EGFR tyrosine kinase inhibitors (TKIs). This review examines the biological rationale and clinical challenges underpinning the development of anti-TROP2 ADCs in EGFR-mutated NSCLC. From a mechanistic standpoint, TROP2 occupies a unique and dynamic role in EGFR-mutated NSCLC, providing strong biological rationale for clinical development of anti-TROP2 ADCs in this population. Three TROP2-directed ADCs are currently in clinical development in this setting. Available clinical data in previously treated EGFR-mutated patients are critically reviewed here, focusing on efficacy, toxicity profiles, clinical challenges and potential future perspectives.<\/jats:p>","DOI":"10.3390\/pharmaceutics18080905","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T17:13:17Z","timestamp":1784826797000},"page":"905","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti-TROP2 Antibody Drug Conjugates in EGFR-Mutant Non-Small Cell Lung Cancer: Biological Rationale and Clinical Challenges"],"prefix":"10.3390","volume":"18","author":[{"given":"Laura","family":"Bonanno","sequence":"first","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy"},{"name":"Medical Oncology 2, Istituto Oncologico Veneto (IOV), IRCCS, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Ronchi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loc Carlo","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pante","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Sangiorgi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Pasello","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy"},{"name":"Medical Oncology 2, Istituto Oncologico Veneto (IOV), IRCCS, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4810-7136","authenticated-orcid":false,"given":"Stefano","family":"Indraccolo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy"},{"name":"Basic and Translational Oncology Unit, Istituto Oncologico Veneto (IOV), IRCCS, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Guarneri","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy"},{"name":"Medical Oncology 2, Istituto Oncologico Veneto (IOV), IRCCS, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104295","DOI":"10.1016\/j.critrevonc.2024.104295","article-title":"The study of primary and acquired resistance to first-line osimertinib to improve the outcome of EGFR-mutated advanced Non-small cell lung cancer patients: The challenge is open for new therapeutic strategies","volume":"196","author":"Ferro","year":"2024","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/s13045-022-01391-4","article-title":"Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance","volume":"15","author":"Fu","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"107917","DOI":"10.1016\/j.pharmthera.2021.107917","article-title":"Stepping forward in antibody-drug conjugate development","volume":"229","author":"Jin","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"35427","DOI":"10.1038\/s41598-025-19362-3","article-title":"Prognostic relevance of TROP2 expression in patients with non-small cell lung cancer receiving immunotherapy","volume":"15","author":"Hashimoto","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.pathol.2023.11.006","article-title":"Prognostic and predictive biomarkers in non-small cell lung carcinoma","volume":"56","author":"Odintsov","year":"2024","journal-title":"Pathology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5310","DOI":"10.7150\/jca.57711","article-title":"Trop2 binding IGF2R induces gefitinib resistance in NSCLC by remodeling the tumor microenvironment","volume":"12","author":"Sun","year":"2021","journal-title":"J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s40265-022-01698-z","article-title":"Targeting Acquired and Intrinsic Resistance Mechanisms in Epidermal Growth Factor Receptor Mutant Non-Small-Cell Lung Cancer","volume":"82","author":"Shah","year":"2022","journal-title":"Drugs"},{"key":"ref_8","first-page":"27","article-title":"Survival with Osimertinib plus Chemotherapy in EGFR-Mutated Advanced NSCLC","volume":"394","author":"Planchard","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1056\/NEJMoa2403614","article-title":"Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC","volume":"391","author":"Cho","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41571-025-01085-z","article-title":"Navigating the landscape of EGFR TKI resistance in EGFR-mutant NSCLC\u2014Mechanisms and evolving treatment approaches","volume":"23","author":"Zhao","year":"2026","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1038\/onc.2012.151","article-title":"The Trop-2 signalling network in cancer growth","volume":"32","author":"Guerra","year":"2013","journal-title":"Oncogene"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"84","DOI":"10.18632\/genesandcancer.40","article-title":"Trop2 and its overexpression in cancers: Regulation and clinical\/therapeutic implications","volume":"6","author":"Shvartsur","year":"2015","journal-title":"Genes Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/emmm.201200222","article-title":"TROP2 is epigenetically inactivated and modulates IGF-1R signalling in lung adenocarcinoma","volume":"4","author":"Lin","year":"2012","journal-title":"EMBO Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1158\/2159-8290.CD-24-1515","article-title":"Eradicating Drug-tolerant Persister Cells in EGFR-Mutated Non\u2013Small Cell Lung Cancer by Targeting TROP2 with CAR-T Cellular Therapy","volume":"15","author":"Baldacci","year":"2025","journal-title":"Cancer Discov."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1158\/2159-8290.CD-25-0960","article-title":"ELIOS: A Multicenter, Molecular Profiling Study of Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer Treated with First-Line Osimertinib","volume":"16","author":"Piotrowska","year":"2026","journal-title":"Cancer Discov."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Martin, M.J., Koers, A., Calero, F., Talbot, S., Hughes, A., Magiera, L., Ireland, L., and Floc\u2019h, N. (2025). Abstract LB458: Osimertinib treatment drives expression of TROP2, and combination treatment with datopotamab deruxtecan (Dato-DXd), a TROP2-directed antibody-drug conjugate, enhances its efficacy in PDX models of EGFR mutant non small-cell lung cancer. Cancer Res., 85.","DOI":"10.1158\/1538-7445.AM2025-LB458"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1016\/j.jtho.2025.06.002","article-title":"A Pooled Analysis of Datopotamab Deruxtecan in Patients With EGFR-Mutated NSCLC","volume":"20","author":"Ahn","year":"2025","journal-title":"J. Thorac. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4678","DOI":"10.1200\/JCO.23.00059","article-title":"First-in-Human, Phase I Dose-Escalation and Dose-Expansion Study of Trophoblast Cell-Surface Antigen 2\u2013Directed Antibody-Drug Conjugate Datopotamab Deruxtecan in Non\u2013Small-Cell Lung Cancer: TROPION-PanTumor01","volume":"41","author":"Garon","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"106763","DOI":"10.1016\/j.esmoop.2026.106763","article-title":"449P Identification of DXd sensitivity biomarkers and osimertinib induced datopotamab deruxtecan (Dato-DXd) internalization as potential mechanisms for enhanced activity of Dato-DXd in preclinical models of EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC)","volume":"11","author":"Sung","year":"2026","journal-title":"ESMO Open"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1158\/1535-7163.MCT-21-0206","article-title":"Datopotamab Deruxtecan, a Novel TROP2-directed Antibody\u2013drug Conjugate, Demonstrates Potent Antitumor Activity by Efficient Drug Delivery to Tumor Cells","volume":"20","author":"Okajima","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1200\/JCO-24-01544","article-title":"Datopotamab Deruxtecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non\u2013Small Cell Lung Cancer: The Randomized, Open-Label Phase III TROPION-Lung01 Study","volume":"43","author":"Ahn","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yasuda, S., Maejima, T., Toki, T., Karibe, T., Okajima, D., and Phillips, P. (2023). Abstract 4893: Evaluation of bystander antitumor effect of Dato-DXd in TROP2 (+) and TROP2 (-) lung cell lines admixed tumor xenograft mouse models. Cancer Res., 83.","DOI":"10.1158\/1538-7445.AM2023-4893"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Huang, J., Wang, X., Zhang, Z., Yan, J., Ma, J., Zhang, M., and Gu, Q. (2025). Abstract 1270: An isogeneic Trop-2 expression heterogeneity model for evaluating the bystander killing effect of anti-Trop-2 ADC. Cancer Res., 85.","DOI":"10.1158\/1538-7445.AM2025-1270"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3843","DOI":"10.1002\/cncr.30789","article-title":"Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics","volume":"123","author":"Ocean","year":"2017","journal-title":"Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cheng, Y., Yuan, X., Tian, Q., Huang, X., Chen, Y., Pu, Y., Long, H., Xu, M., Ji, Y., and Xie, J. (2022). Preclinical profiles of SKB264, a novel anti-TROP2 antibody conjugated to topoisomerase inhibitor, demonstrated promising antitumor efficacy compared to IMMU-132. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.951589"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Nguyen, T.D., Bordeau, B.M., and Balthasar, J.P. (2023). Mechanisms of ADC Toxicity and Strategies to Increase ADC Tolerability. Cancers, 15.","DOI":"10.3390\/cancers15030713"},{"key":"ref_27","unstructured":"(2026, June 25). Clinical Overview of Trophoblast Surface Antigen 2 Antibody-Drug Conjugates in Non\u2013Small Cell Lung Cancer\u2014ClinicalKey. Available online: https:\/\/www.clinicalkey.com\/#!\/content\/playContent\/1-s2.0-S0305737225001720?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0305737225001720%3Fshowall%3Dtrue&referrer=."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s13045-023-01519-0","article-title":"Considerations for the design of antibody drug conjugates (ADCs) for clinical development: Lessons learned","volume":"16","author":"Sanvicente","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Buyukgolcigezli, I., Tenekeci, A.K., and Sahin, I.H. (2025). Opportunities and Challenges in Antibody\u2013Drug Conjugates for Cancer Therapy: A New Era for Cancer Treatment. Cancers, 17.","DOI":"10.20944\/preprints202502.1917.v1"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1200\/JCO-24-01349","article-title":"Datopotamab Deruxtecan in Advanced or Metastatic Non\u2013Small Cell Lung Cancer With Actionable Genomic Alterations: Results From the Phase II TROPION-Lung05 Study","volume":"43","author":"Sands","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.annonc.2026.02.014","article-title":"Osimertinib plus datopotamab deruxtecan in patients with EGFR-mutated advanced NSCLC after progression on first-line osimertinib: ORCHARD","volume":"37","author":"Riess","year":"2026","journal-title":"Ann. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"17588359251385410","DOI":"10.1177\/17588359251385410","article-title":"TROPION-Lung15: A randomized phase III study of osimertinib combined with datopotamab deruxtecan (Dato-DXd) or Dato-DXd alone versus platinum-doublet chemotherapy in patients with EGFR-mutated advanced non-small cell lung cancer and whose disease has progressed on prior osimertinib","volume":"17","author":"Tan","year":"2025","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_33","unstructured":"(2026, April 01). A Phase III, Open-Label, Randomised Study of Osimertinib With or Without Datopotamab Deruxtecan (Dato-DXd), as First-Line Treatment in Participants with Epidermal Growth Factor Receptor (EGFR) Mutation-Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer. Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06350097."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1038\/s41591-025-03638-2","article-title":"Sacituzumab tirumotecan in advanced non-small-cell lung cancer with or without EGFR mutations: Phase 1\/2 and phase 2 trials","volume":"31","author":"Zhao","year":"2025","journal-title":"Nat. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Fang, W., Li, X., Wang, Q., Meng, X., Zheng, W., Sun, L., Yao, W., Zhuang, W., Fan, Y., and Zhuo, M. (2025). Sacituzumab tirumotecan versus docetaxel for previously treated EGFR-mutated advanced non-small cell lung cancer: Multicentre, open label, randomised controlled trial. BMJ, 389, Erratum in BMJ\u00a02025, 391, r2300.","DOI":"10.1136\/bmj.r2300"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa2512071","article-title":"Sacituzumab Tirumotecan in EGFR-TKI\u2013Resistant, EGFR-Mutated Advanced NSCLC","volume":"394","author":"Fang","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"108914","DOI":"10.1016\/j.lungcan.2026.108914","article-title":"Comparative efficacy and safety of post-TKI treatments for advanced EGFR-mutant non-small-cell lung cancer: A systematic review and network meta-analysis","volume":"212","author":"Wang","year":"2026","journal-title":"Lung Cancer"},{"key":"ref_38","unstructured":"Chen, L.K. (2026, April 01). Sacituzumab Tirumotecan (Sac-TMT) Plus Bevacizumab in 3rd Generation EGFR-TKI Treated Advanced EGFR-Mutant Nonsquamous NSCLC with Brain Metastasis: A Single-Arm, Phase II Study (TOP BRAIN). Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/study\/NCT07197008."},{"key":"ref_39","unstructured":"Wang, J. (2026, April 01). A Multicenter, Single-Arm, Phase II Clinical Study of Sacituzumab Tirumotecan in Combination with Furmonertinib as Second-Line Treatment for EGFR-Mutant Advanced or Metastatic NSCLC After Failure of First-Line Third-Generation EGFR-TKI Therapy. Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/study\/NCT07193160."},{"key":"ref_40","unstructured":"Zhang, P. (2026, April 01). Sacituzumab Tirumotecan and Limertinib for Conversion Therapy in Locally Advanced Potentially Resectable EGFR-Mutant Non-Small Cell Lung Cancer: A Prospective, Single-Arm, Exploratory Clinical Study. Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/study\/NCT07323056."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2860","DOI":"10.1200\/JCO.24.00733","article-title":"Sacituzumab Govitecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non\u2013Small Cell Lung Cancer: The Randomized, Open-Label Phase III EVOKE-01 Study","volume":"42","author":"Mountzios","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Reyes, A., Pharaon, R., Mohanty, A., and Massarelli, E. (2023). Arising Novel Agents in Lung Cancer: Are Bispecifics and ADCs the New Paradigm?. Cancers, 15.","DOI":"10.3390\/cancers15123162"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"102902","DOI":"10.1016\/j.ctrv.2025.102902","article-title":"Antibody-drug conjugates in NSCLC with actionable genomic alterations: Optimizing smart delivery of chemotherapy to the target","volume":"134","author":"Mountzios","year":"2025","journal-title":"Cancer Treat. Rev."},{"key":"ref_44","first-page":"oyaf031","article-title":"Prophylaxis, clinical management, and monitoring of datopotamab deruxtecan-associated oral mucositis\/stomatitis","volume":"30","author":"Bardia","year":"2025","journal-title":"Oncologist"},{"key":"ref_45","unstructured":"(2026, April 01). A Phase IV, Open-Label, Single-Arm Study of Prophylaxis for Datopotamab Deruxtecan-Related Stomatitis in Eligible Patients with Metastatic or Inoperable Locally Recurrent Breast Cancer or Locally Advanced or Metastatic Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer (TROPION-SWISH). Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/study\/NCT07357597."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.2147\/DDDT.S508773","article-title":"A Systematic Review of Mechanisms, Incidence, and Management of Trastuzumab Deruxtecan Induced ILD\/Pneumonitis in Solid Tumors","volume":"19","author":"Liao","year":"2025","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8623","DOI":"10.21037\/jtd-2025-583","article-title":"Efficacy and safety of datopotamab deruxtecan in advanced\/metastatic non-small cell lung cancer patients: A systematic review and single-arm meta-analysis","volume":"17","author":"Kim","year":"2025","journal-title":"J. Thorac. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"103688","DOI":"10.1016\/j.jtho.2026.103688","article-title":"Datopotamab Deruxtecan Plus Pembrolizumab With or Without Platinum-Based Chemotherapy for Advanced or Metastatic NSCLC: The Phase Ib TROPION-Lung02 Trial","volume":"21","author":"Levy","year":"2026","journal-title":"J. Thorac. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Patel, J.D., Zavodovskaya, M., Cho, B.C., Reck, M., Gray, J.E., Reguart, N., Felip, E., Neal, J.W., Lin, K.-W., and J\u00fcrgensmeier, J.M. (2025). Abstract LB399: Trop-2 expression and association with efficacy in patients treated with sacituzumab govitecan + pembrolizumab +\/- carboplatin in the EVOKE-02 study of non-small cell lung cancer. Cancer Res., 85.","DOI":"10.1158\/1538-7445.AM2025-LB399"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1200\/JCO.2023.41.16_suppl.1082","article-title":"Trop-2 mRNA expression and association with clinical outcomes with sacituzumab govitecan (SG) in patients with HR+\/HER2\u2013 metastatic breast cancer (mBC): Biomarker results from the phase 3 TROPiCS-02 study","volume":"41","author":"Bardia","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Garassino, M.C., Kuo, P., Reinmuth, N., Girard, N., Mountzios, G., Provencio, M., Summers, Y., Tiseo, M., Tang, S., and Patel, R. (2025). Abstract LB260: Potential prognostic\/predictive biomarkers for sacituzumab govitecan in EVOKE-01. Cancer Res., 85.","DOI":"10.1158\/1538-7445.AM2025-LB260"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S1305","DOI":"10.1016\/j.annonc.2023.10.061","article-title":"LBA12 Datopotamab deruxtecan (Dato-DXd) vs docetaxel in previously treated advanced\/metastatic (adv\/met) non-small cell lung cancer (NSCLC): Results of the randomized phase III study TROPION-Lung01","volume":"34","author":"Ahn","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_53","unstructured":"(2026, April 01). Novel Computational Pathology-Based TROP2 Biomarker for Datopotamab Deruxtecan was Predictive of Clinical Outcomes in Patients with Non-Small Cell Lung Cancer in TROPION-Lung01 Phase III Trial. Available online: https:\/\/www.astrazeneca.com\/content\/astraz\/media-centre\/press-releases\/2024\/novel-computational-pathology-based-trop2-biomarker-for-dato-dxd-was-predictive-of-clinical-outcomes-in-patients-with-nsclc-in-tropion-lung01-phase-iii-trial.html."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Sung, M.S., Wilson, M., Vonficht, D., Meier, A., Rane, C., Dunlop, C., Patel, G., Przybyla, A., Wallez, Y., and Liu, X. (2025). Abstract 7149: The role of TROP2 in the MoA of Dato-DXd and how it underpins the biologic rationale of the novel AI-guided biomarker TROP2 normalized membrane ratio. Cancer Res., 85.","DOI":"10.1158\/1538-7445.AM2025-7149"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"106349","DOI":"10.1016\/j.esmoop.2026.106349","article-title":"42P TROP2 normalised membrane ratio (NMR) assessed by quantitative continuous scoring (QCS): Association with clinical outcomes with datopotamab deruxtecan (Dato-DXd) \u00b1 osimertinib (osi) in EGFR-mutated (EGFRm) NSCLC","volume":"11","author":"Sands","year":"2026","journal-title":"ESMO Open"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4591","DOI":"10.1200\/JCO.2025.43.16_suppl.4591","article-title":"First survival outcomes and biomarker results of SURE-01: Neoadjuvant sacituzumab govitecan (SG) monotherapy, followed by radical cystectomy (RC), in patients with muscle-invasive urothelial bladder cancer (MIBC)","volume":"43","author":"Maiorano","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1200\/JCO.2024.42.16_suppl.1075","article-title":"Genomic alterations in DNA damage response (DDR) genes in HR+\/HER2- metastatic breast cancer (mBC) and impact on clinical efficacy with sacituzumab govitecan (SG): Biomarker results from TROPICS-02 study","volume":"42","author":"Bardia","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"105807","DOI":"10.1016\/j.esmoop.2025.105807","article-title":"COMPEL: Osimertinib plus platinum-based chemotherapy in patients with EGFR-mutated advanced NSCLC and progression on first-line osimertinib","volume":"10","author":"Peled","year":"2025","journal-title":"ESMO Open"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.annonc.2023.10.117","article-title":"Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: Primary results from the phase III MARIPOSA-2 study","volume":"35","author":"Passaro","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_60","unstructured":"(2024). HARMONi-A Study Investigators. Ivonescimab Plus Chemotherapy in Non\u2013Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial. JAMA, 332, 561\u2013570."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8506","DOI":"10.1200\/JCO.2025.43.16_suppl.8506","article-title":"Patritumab deruxtecan (HER3-DXd) in resistant EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC) after a third-generation EGFR TKI: The phase 3 HERTHENA-Lung02 study","volume":"43","author":"Mok","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"(2023). HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in Epidermal Growth Factor Receptor\u2013Mutated Non\u2013Small-Cell Lung Cancer After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy. J. Clin. Oncol., 41, 5363\u20135375.","DOI":"10.1200\/JCO.23.01476"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.annonc.2026.01.009","article-title":"Izalontamab brengitecan (Iza-bren; BL-B01D1), a first-in-class EGFR-HER3 bispecific antibody\u2013drug conjugate, for patients with EGFR-mutated NSCLC: Pooled analysis of phase I and phase II trials","volume":"37","author":"Hong","year":"2026","journal-title":"Ann. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1056\/NEJMoa2306434","article-title":"Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC","volume":"389","author":"Planchard","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/s41416-022-01777-8","article-title":"Liquid biopsy and non-small cell lung cancer: Are we looking at the tip of the iceberg?","volume":"127","author":"Bonanno","year":"2022","journal-title":"Br. J. Cancer."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.annonc.2024.05.541","article-title":"Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: A secondary analysis from MARIPOSA","volume":"35","author":"Felip","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1016\/j.jtho.2024.07.008","article-title":"Longitudinal Analyses of Circulating Tumor DNA for the Detection of EGFR Mutation-Positive Advanced NSCLC Progression During Treatment: Data From FLAURA and AURA3","volume":"19","author":"Gray","year":"2024","journal-title":"J. Thorac. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/s41698-024-00704-9","article-title":"Longitudinal liquid biopsy predicts clinical benefit from immunotherapy in advanced non-small cell lung cancer","volume":"8","author":"Zulato","year":"2024","journal-title":"npj Precis. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1038\/s41416-022-01978-1","article-title":"Longitudinal liquid biopsy anticipates hyperprogression and early death in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors","volume":"127","author":"Zulato","year":"2022","journal-title":"Br. J. Cancer."},{"key":"ref_70","unstructured":"Guangdong Association of Clinical Trials (2026, April 01). A ctDNA-Guided Phase II Trial of Osimertinib in Combination with Sacituzumab Tirumotecan in EGFR-Mutated Advanced NSCLC Patients with Positvie ctDNA After Lead-in Osimertinib Monotherapy. Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/study\/NCT07375316."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/8\/905\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:32:31Z","timestamp":1784953951000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/8\/905"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":70,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["pharmaceutics18080905"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18080905","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]}}}