{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:50:34Z","timestamp":1786114234907,"version":"build-2736575974"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"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":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>\n                    The minimal anticipated biological effect level (MABEL) approach to first\u2010in\u2010human (FIH) dose calculation can lead to long dose\u2010escalation periods before observing clinical activity. We used a novel\n                    <jats:italic>ex vivo<\/jats:italic>\n                    MABEL approach to calculate the FIH starting dose for forimtamig, a T\u2010cell bispecific antibody under investigation for the treatment of relapsed\/refractory multiple myeloma (RRMM). We used\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>ex vivo<\/jats:italic>\n                    MABEL approaches to calculate the FIH dose for a Phase 1 trial (NCT04557150) in patients with RRMM.\n                    <jats:italic>In vitro<\/jats:italic>\n                    assays used the OPM\u20102\u2009MM cell line and peripheral blood mononucleocytes from healthy donors and patients with MM.\n                    <jats:italic>Ex vivo<\/jats:italic>\n                    assays used fresh bone marrow aspirates from MM patient donors. Forimtamig increased tumor cell lysis, cytokine release, and T\u2010cell activation\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>ex vivo<\/jats:italic>\n                    . Tumor cell lysis was considered the most relevant assay for dose calculation. EC\n                    <jats:sub>50<\/jats:sub>\n                    for LDH release (\n                    <jats:italic>in vitro<\/jats:italic>\n                    : mean 0.6 pM;\n                    <jats:italic>ex vivo<\/jats:italic>\n                    : 9 pM for the most sensitive patient) led to calculated FIH starting doses of 0.4 and 6\u2009\u03bcg, respectively. FIH starting dose was 6\u2009\u03bcg. Clinical activity was observed in the second dosing cohort (18 and 54\u2009\u03bcg). The third dosing cohort (54 and 162\u2009\u03bcg) showed durable objective responses. Cytokine release syndrome was Grade 1 at the starting dose and absent in the second dosing cohort. Our\n                    <jats:italic>ex vivo<\/jats:italic>\n                    MABEL approach was accepted by regulatory authorities and yielded a tolerated forimtamig FIH starting dose which demonstrated clinical activity in the second dosing cohort. We encourage similar innovative patient\u2010centric approaches to FIH dose calculation.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70366","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T03:21:57Z","timestamp":1781752917000},"page":"745-752","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Patient\u2010Centric First\u2010in\u2010Human Dose Selection: An Ex\u00a0Vivo Minimal Anticipated Biological Effect Level Approach for T\u2010Cell Engagers in Multiple Myeloma"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5528-3197","authenticated-orcid":false,"given":"Thomas E.","family":"Kraft","sequence":"first","affiliation":[{"name":"Roche Pharma Research &amp; Early Development Roche Innovation Center Munich  Penzberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9677-0549","authenticated-orcid":false,"given":"Estelle","family":"Marrer\u2010Berger","sequence":"additional","affiliation":[{"name":"Roche Pharma Research &amp; Early Development Roche Innovation Center Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5435-0554","authenticated-orcid":false,"given":"Sara","family":"Belli","sequence":"additional","affiliation":[{"name":"Roche Pharma Research &amp; Early Development Roche Innovation Center Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4792-4000","authenticated-orcid":false,"given":"Helene","family":"Haegel","sequence":"additional","affiliation":[{"name":"Roche Pharma Research &amp; Early Development Roche Innovation Center Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3350-5106","authenticated-orcid":false,"given":"Anneliese","family":"Schneider","sequence":"additional","affiliation":[{"name":"Roche Pharma Research &amp; Early Development Roche Innovation Center Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3067-778X","authenticated-orcid":false,"given":"Anna Maria","family":"Giusti","sequence":"additional","affiliation":[{"name":"Roche Pharma Research &amp; Early Development Roche Innovation Center Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7808-3270","authenticated-orcid":false,"given":"Michael","family":"Bscheider","sequence":"additional","affiliation":[{"name":"Roche Pharma Research &amp; Early Development Roche Innovation Center Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8171-7542","authenticated-orcid":false,"given":"Wolfgang","family":"Jacob","sequence":"additional","affiliation":[{"name":"Roche Pharma Research &amp; Early Development Roche Innovation Center Munich  Penzberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Weisser","sequence":"additional","affiliation":[{"name":"Roche Pharma Research &amp; Early Development Roche Innovation Center Munich  Penzberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1859-0884","authenticated-orcid":false,"given":"Laura","family":"Blanco","sequence":"additional","affiliation":[{"name":"Cancer Center Cl\u00ednica Universidad de Navarra, Centro de Investigaci\u00f3n M\u00e9dica Aplicada, University of Navarra, IDISNA, CIBERONC  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Frances","sequence":"additional","affiliation":[{"name":"Roche Pharma Research &amp; 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