{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:30:33Z","timestamp":1788517833261,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004331","name":"Johnson and Johnson","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p>Talquetamab is the first and only GPRC5D\u2009\u00d7\u2009CD3 bispecific antibody approved for relapsed\/refractory multiple myeloma (RRMM). In the phase I\/II MonumenTAL\u20101 study, overall response rates (ORRs) were &gt;\u200966% in patients with RRMM treated with subcutaneous talquetamab at the recommended phase II doses (RP2Ds): 0.4\u2009mg\/kg weekly and 0.8\u2009mg\/kg every other week. We characterized the pharmacokinetics (PK), pharmacodynamics, immunogenicity, and exposure\u2010response relationships for efficacy and safety following talquetamab administration in phase I and II. In phase I, talquetamab exposure increased in an approximately dose\u2010proportional manner across intravenous and subcutaneous doses and was maintained around or above the 90% maximum effective concentration identified in an ex\u00a0vivo cytotoxic assay at the RP2Ds. Higher levels of T\u2010cell activation and cytokine induction were observed at the RP2Ds compared with lower doses. Talquetamab demonstrated time\u2010dependent clearance with a half\u2010life of 7.56\u2009days at initial treatment and 12.2\u2009days at steady state. Patients with immunoglobulin G multiple myeloma and International Staging System (ISS) stage II\/III exhibited higher clearance of talquetamab, which resulted in lower exposure. Dose adjustment based on myeloma subtype and ISS stage was not required. In exposure\u2010response analyses, a near\u2010flat relationship was demonstrated for ORR, duration of response, and progression\u2010free survival at the exposure range of the RP2Ds. In safety exposure\u2010response analyses, rates of grade 1\/2 dysgeusia increased with higher exposures. The incidence of anti\u2010talquetamab antibodies had no apparent impact on the PK, efficacy, or safety of talquetamab. These clinical pharmacology results support the selection of the talquetamab RP2Ds.<\/jats:p>","DOI":"10.1002\/cpt.70004","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T09:04:56Z","timestamp":1753347896000},"page":"954-966","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Recommended Phase II Doses of Talquetamab in Patients With Relapsed\/Refractory Multiple Myeloma From MonumenTAL\u20101: Clinical Pharmacology Results"],"prefix":"10.1002","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6143-7755","authenticated-orcid":false,"given":"Jue","family":"Gong","sequence":"first","affiliation":[{"name":"Johnson &amp; Johnson  Spring House Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Spring House Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongfen","family":"Yuan","sequence":"additional","affiliation":[{"name":"Johnson &amp; 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Johnson  Spring House Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus","family":"Berdeja","sequence":"additional","affiliation":[{"name":"Sarah Cannon and Tennessee Oncology Research Institute  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrita","family":"Krishnan","sequence":"additional","affiliation":[{"name":"City of Hope Cancer Center  Duarte California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Ouellet","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Spring House Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25791"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2021.09.013"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.11.014"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0435-7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.196"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S370880"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2203478"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1101495"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204591"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(24)00385-5"},{"key":"e_1_2_9_11_1","unstructured":"European Medicines Agency.TALVEY (talquetamab). <https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/talvey> (2023). Accessed November 29 2023."},{"key":"e_1_2_9_12_1","unstructured":"Janssen Biotech.TALVEY\u2122 (talquetamab\u2010tgvs) prescribing information. <https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/761342s000lbl.pdf> (2023). Accessed June 19 2024."},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003805"},{"key":"e_1_2_9_14_1","doi-asserted-by":"crossref","unstructured":"Goldsmith R.B.et al.Normal human tissue expression of G protein\u2013coupled receptor class C group 5 member D (GPRC5D) a promising novel target for multiple myeloma is restricted to plasma cells and hard keratinized tissues. 18th International Myeloma Society Annual Meeting; September 8\u201311 2021; Vienna Austria.","DOI":"10.1016\/S2152-2650(21)02229-1"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003342"},{"key":"e_1_2_9_16_1","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez\u2010Otero P.et al.Analysis of infection and parameters of humoral immunity in patients with relapsed\/refractory multiple myeloma treated with talquetamab monotherapy in MonumenTAL\u20101. American Society of Clinical Oncology (ASCO) Annual Meeting; June 2\u20136 2023; Chicago IL USA.","DOI":"10.1200\/JCO.2023.41.16_suppl.8020"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2026131"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S150524"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-018-0343-9"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30206-6"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-299487"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.zemedi.2009.05.003"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011970125687"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.2165\/11535960-000000000-00000"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.2165\/11531280-000000000-00000"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-023-00989-z"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12143"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-162859"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-018-0815-9"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1208\/aapsj070351"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.2165\/11593210-000000000-00000"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12049"},{"key":"e_1_2_9_33_1","unstructured":"TECVAYLI\u2122 (teclistamab\u2010cqyv). 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American Conference on Pharmacometrics (ACoP); November 5\u20138 Oxon Hill MD USA2024."},{"key":"e_1_2_9_39_1","article-title":"S193: BMS\u2010986393 (CC\u201095266), a G protein\u2013coupled receptor class C group 5 member D (GPRC5D)\u2013targeted CAR T\u2010cell therapy for relapsed\/refractory multiple myeloma (RRMM): results from a phase 1 study","volume":"7","author":"Bal S.","year":"2023","journal-title":"Blood"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-157988"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2024.05.003"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2209900"},{"key":"e_1_2_9_43_1","doi-asserted-by":"crossref","unstructured":"Chari A.et al.Efficacy and safety of less frequent\/lower intensity dosing of talquetamab in patients with relapsed\/refractory multiple myeloma: results from the phase 1\/2 MonumenTAL\u20101 study. 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