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A comprehensive population pharmacokinetics analysis using cumulative data from 998 patients across 10 clinical studies characterized savolitinib pharmacokinetics, its variability, and the impact of intrinsic and extrinsic factors. In a covariate search, no retained covariates had a clinically meaningful impact on steady\u2010state exposure of savolitinib. Model\u2010predicted savolitinib exposures were used to evaluate the relationship between savolitinib exposure and efficacy endpoints in the SAVANNAH Phase II study (NCT03778229;\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009360), in subpopulations defined by MET biomarker status. Among patients treated with savolitinib 300\u2009mg once daily, 600\u2009mg once daily, or 300\u2009mg twice daily with osimertinib 80\u2009mg once daily in SAVANNAH, a positive trend was observed between the trough concentration (Cmin,ss) at steady state and the objective response rate in all\u2010comer population, whereas no clear trend was observed in patients with high MET biomarker status, defined as MET immunohistochemistry (IHC) 3+\/\u2265\u200990% and\/or fluorescence in\u00a0situ hybridization (FISH) 10+. These findings support Cmin,ss as the exposure metric most informative for maintaining MET target coverage and for guiding a trough\u2010driven dosing strategy. Exposure\u2013safety relationships were assessed across all 10 studies and no statistically significant associations were identified between savolitinib exposure and the occurrence of most safety events. These integrated population pharmacokinetics and exposure\u2013response findings provide supportive evidence relevant to dose evaluation and clinical development of savolitinib in combination with osimertinib.\n                  <\/jats:p>","DOI":"10.1111\/cts.70700","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:00:42Z","timestamp":1787634042000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetics and Exposure\u2010Response Analyses of Savolitinib Alone or in Combination With Osimertinib in Patients With Locally Advanced or Metastatic Solid Tumors"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0678-311X","authenticated-orcid":false,"given":"Azar","family":"Shahraz","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology Clinical Pharmacology and Safety Sciences, R&amp;D, 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