{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T13:04:02Z","timestamp":1784379842941,"version":"3.55.0"},"reference-count":19,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Favezelimab (MK\u20104280) is a humanized monoclonal antibody (mAb) targeting lymphocyte activation gene\u20103 (LAG\u20103). Favezelimab population pharmacokinetics (popPK) was evaluated using data from 2 trials; a Phase 1 study evaluating favezelimab across a range of doses (7 to 800\u2009mg administered intravenously [IV] every 3\u2009weeks [Q3W]) in patients with advanced solid tumors, and a Phase 3 study evaluating 800\u2009mg IV Q3W favezelimab combined with pembrolizumab (200\u2009mg Q3W) in patients with programmed death ligand 1 (PD\u2010L1) positive colorectal cancer (CRC). Prespecified covariates of clinical interest were evaluated using a full model. Favezelimab exposure measures from the final popPK model were used to evaluate the exposure\u2010response (E\u2010R) relationships with objective response rate (ORR), Grade \u2265\u20093 drug\u2010related adverse events (AE), and drug\u2010related AE of special interest (AEOSI) occurrence in gastric cancer patients evaluated across 2 randomized doses. The final popPK model was a 2\u2010compartment target\u2010mediated drug disposition (TMDD) model and included the effect of antidrug antibody status on linear clearance (CL). Population volume and clearance parameters, and corresponding random effects were estimated with &lt;\u200915% relative standard error. Lower body weight, as well as female sex and Asian race (covariates correlated with lower body weight), were associated with higher exposure. Lower albumin levels were also associated with lower exposure. Increasing favezelimab exposures were associated with increased ORR and had no significant effect on safety. No covariates were associated with ORR. This analysis was used to characterize variability in favezelimab pharmacokinetics and support the choice of Phase 3 dose.<\/jats:p>","DOI":"10.1111\/cts.70658","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T12:30:00Z","timestamp":1783081800000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetic, Exposure\u2010Response Efficacy and Safety Analyses of Favezelimab in Patients With Solid Tumors"],"prefix":"10.1111","volume":"19","author":[{"given":"Mitali","family":"Gaurav","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Pharmacometric Solutions Simulations Plus, Inc  Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Barcomb","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometric Solutions Simulations Plus, Inc  Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly F.","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometric Solutions Simulations Plus, Inc  Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5466-0897","authenticated-orcid":false,"given":"Bhargava","family":"Kandala","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manash S.","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.08.010"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0161-5890(90)90097-J"},{"key":"e_1_2_10_4_1","first-page":"269","article-title":"LAG\u20103 in Cancer Immunotherapy","volume":"344","author":"Goldberg M. V.","year":"2011","journal-title":"Current Topics in Microbiology and Immunology"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2022-1105"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-024-00671-0"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024014654"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2022.100639"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-017-9528-y"},{"key":"e_1_2_10_10_1","unstructured":"M. R.Gastonguay \u201cFull Covariate Models as an Alternative to Methods Relying on Statistical Significance for Inferences About Covariate Effects: A Review of Methodology and 42 Case Studies\u201d. Poster Presented at: PAGE; 2011 June 7\u201310; Athens Greece."},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-011-9255-z"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-008-9102-8"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13996"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2025.2512217"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/antib8040056"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/9783527634057.ch4"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-005670"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12224"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-1683"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13676"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70658","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.70658","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70658","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T12:52:11Z","timestamp":1784379131000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":19,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/cts.70658"],"URL":"https:\/\/doi.org\/10.1111\/cts.70658","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-02-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70658"}}