{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:38:51Z","timestamp":1786977531507,"version":"build-2736575974"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2023,5,15]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n SH\u20101028 is a new third\u2010generation EGFR tyrosine kinase inhibitors (TKI) to benefit patients with\n EGFR<\/jats:italic>\n T790M\u2010mutated NSCLC. Here, the authors report its clinical safety, preliminary efficacy, and pharmacokinetic (PK) profile for the first time.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Patients with\n EGFR<\/jats:italic>\n T790M mutation, locally advanced non\u2013small cell lung cancer (NSCLC), or metastatic NSCLC who had progressed after previous EGFR TKI therapy were eligible. Patients received SH\u20101028 at five oral dose levels (60\u00a0mg, 100\u00a0mg, 200 mg, 300 mg, and 400\u00a0mg) once daily until disease progression, unacceptable toxicity, or patient withdrawal. The primary end points were the safety, dose\u2010limiting toxicity (DLT), maximum\u2010tolerated dose (MTD), and PK profile. Secondary end points included objective response rate (ORR), disease control rate (DCR), progression\u2010free survival (PFS), etc.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Data cut off on December 31, 2020, a total of 20 patients were enrolled during the trial, two of\u00a0three\u00a0patients in 300\u00a0mg cohort experienced a DLT, and no DLT was observed in 240\u00a0mg cohort, 240\u00a0mg was determined to be the MTD of SH\u20101028. A total of 95.0% (19 of 20) of patients reported treatment\u2010related adverse events (TRAEs), and the incidence of serious adverse events was 20.0% (4 of 20). The ORR and DCR of the 200\u00a0mg cohort were 75% (95% confidence interval [CI], 19.41\u201399.37) and 75.0% (95% CI, 19.41\u201399.37), respectively. The overall ORR was 40% (95% CI, 19.12\u201363.95), and DCR was 70.0% (95% CI, 45.72\u201388.11). According to the PK profile, the dosage regimen for future studies was determined as 200\u00a0mg once daily.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n SH\u20101028 showed a manageable safety and promising antitumor activity in patients with\n EGFR<\/jats:italic>\n T790M mutation at the dose of 200\u00a0mg once daily.\n <\/jats:p>\n <\/jats:sec>\n \n Plain language summary<\/jats:title>\n \n \n \n Lung cancer has a high morbidity and mortality, with an estimated 1.8 million deaths in 2020. Non\u2013small cell lung cancer accounts for approximately 85% of lung cancer.<\/jats:p>\n <\/jats:list-item>\n \n First\u2010 or second\u2010generation EGFR TKIs' weak selectivity often led to the occurrence of treatment\u2010related adverse events, such as interstitial lung disease, rash, diarrhea, etc., along with acquired drug resistance within approximately 1\u00a0year.<\/jats:p>\n <\/jats:list-item>\n \n A dose of 200\u00a0mg of SH\u20101028 once daily showed a preliminary antitumor activity with manageable safety in patients with EGFR T790M mutation.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cncr.34697","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T22:29:45Z","timestamp":1677104985000},"page":"1513-1522","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Safety, efficacy, and pharmacokinetics of SH\u20101028 in\n EGFR<\/i>\n T790M\u2010positive advanced non\u2013small cell lung cancer patients: A dose\u2010escalation phase 1 study"],"prefix":"10.1002","volume":"129","author":[{"given":"Jing","family":"He","sequence":"first","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Nanjing Medical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Nanjing Medical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Nanjing Sanhome Pharmaceutical Company, Ltd Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinsheng","family":"Shi","sequence":"additional","affiliation":[{"name":"Nanjing Sanhome Pharmaceutical Company, Ltd Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renhua","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Nanjing Medical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Nanjing Medical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqian","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Nanjing Medical University Nanjing 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