{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T18:22:43Z","timestamp":1772994163791,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Sotorasib is a small molecule KRAS\n                    <jats:sup>G12C<\/jats:sup>\n                    inhibitor approved for the treatment of KRAS\n                    <jats:sup>G12C<\/jats:sup>\n                    mutated locally advanced or metastatic non\u2010small cell lung cancer in adult patients. The effect of hepatic impairment on the pharmacokinetics (PK) of sotorasib and major metabolites M10, M18, and M24, safety, and tolerability after a single oral dose of 960 mg was assessed in a phase 1, parallel\u2010arm, multi\u2010center (US), open\u2010label study. Sotorasib AUC\n                    <jats:sub>inf<\/jats:sub>\n                    ratio for subjects with moderate (n = 7) or severe (n = 4) hepatic impairment relative to normal hepatic function (n = 7) was 0.746 (90% CI: 0.431\u20101.29) and 1.04 (0.545\u20101.97), respectively. C\n                    <jats:sub>max<\/jats:sub>\n                    ratio for moderate and sever hepatic impairment was 0.955 (0.512\u20101.78) and 1.43 (0.688\u20102.96), respectively. Mean t\n                    <jats:sub>1\/2<\/jats:sub>\n                    values for sotorasib were similar in subjects with normal hepatic function and subjects with moderate or severe hepatic impairment. C\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>inf<\/jats:sub>\n                    of M10 and M24 increased, while M18 decreased with increasing severity of hepatic impairment. Treatment\u2010emergent adverse events were mild in severity and no serious adverse events were reported. Overall, moderate or severe hepatic impairment did not considerably affect the exposure of sotorasib, M10, M18, and M24. This data supports that adjustments to sotorasib dosing are not indicated for moderate or severe hepatic impairment.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70095","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T08:50:58Z","timestamp":1755679858000},"page":"1864-1875","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Impact of Hepatic Impairment on the Pharmacokinetics of Sotorasib and Its Major Metabolites: Implications for Dose Adjustment"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9871-8616","authenticated-orcid":false,"given":"Mason","family":"McComb","sequence":"first","affiliation":[{"name":"Amgen Inc.  Thousand Oaks CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panli","family":"Cardona","sequence":"additional","affiliation":[{"name":"Amgen Inc.  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