{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:04:45Z","timestamp":1791813885661,"version":"4.3.4"},"reference-count":55,"publisher":"American Society of Hematology","issue":"2","license":[{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1,9]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Despite several approved therapies, multiple myeloma (MM) remains an incurable disease with high unmet medical need. \u201cOff-the-shelf\u201d T-cell bispecific antibodies (TCBs) targeting B-cell maturation antigen (BCMA) and G protein\u2013coupled receptor class C group 5\u00a0member D (GPRC5D) have demonstrated high objective response rates in heavily pretreated patients with MM; however, primary resistance, short duration of response, and relapse driven by antigen shift frequently occur. Although GPRC5D represents the most selective target in MM, recent findings indicate antigen loss occurs more frequently than with BCMA. Thus, anti-GPRC5D immunotherapies must hit hard during a short period of time. Here, we characterize forimtamig, a novel GPRC5D-targeting TCB with 2+1 format. Bivalent binding of forimtamig to GPRC5D confers higher affinity than classical 1+1 TCB formats correlating with formation of more stable immunological synapses and higher potency in tumor cell killing and T-cell activation. Using an orthotopic mouse model of MM, forimtamig recruited T effector cells to the bone marrow and induced rapid tumor killing even after the introduction of step-up dosing to mitigate cytokine release. Combination of forimtamig with standard-of-care agents including anti-CD38 antibodies, immunomodulatory drugs, and proteasome inhibitors improved depth and duration of response. The combination of forimtamig with novel therapeutic agents including BCMA TCB and cereblon E3 ligase modulatory drugs was potent and prevented occurrence of GPRC5D -negative tumor relapse. Forimtamig is currently being evaluated in phase 1 clinical trials in patients with relapsed and refractory MM for monotherapy and in combination treatments. This trial was registered at www.ClinicalTrials.gov as #NCT04557150.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2024025987","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T18:39:29Z","timestamp":1730313569000},"page":"202-219","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":32,"title":["Forimtamig, a novel GPRC5D-targeting T-cell bispecific antibody with a 2+1 format, for the treatment of multiple myeloma"],"prefix":"10.1182","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0829-9576","authenticated-orcid":false,"given":"Jan","family":"Eckmann","sequence":"first","affiliation":[{"name":"1Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Fauti","sequence":"additional","affiliation":[{"name":"2Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene","family":"Biehl","sequence":"additional","affiliation":[{"name":"2Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aintzane","family":"Zabaleta","sequence":"additional","affiliation":[{"name":"3Cl\u00ednica Universidad de Navarra, Centro de Investigaci\u00f3n M\u00e9dica Aplicada, University of Navarra, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1859-0884","authenticated-orcid":false,"given":"Laura","family":"Blanco","sequence":"additional","affiliation":[{"name":"3Cl\u00ednica Universidad de Navarra, Centro de Investigaci\u00f3n M\u00e9dica Aplicada, University of Navarra, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8502-0689","authenticated-orcid":false,"given":"Iva","family":"Lelios","sequence":"additional","affiliation":[{"name":"4Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Gottwald","sequence":"additional","affiliation":[{"name":"1Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Rae","sequence":"additional","affiliation":[{"name":"1Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Lechner","sequence":"additional","affiliation":[{"name":"1Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christa","family":"Bayer","sequence":"additional","affiliation":[{"name":"1Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quincy","family":"Dekempe","sequence":"additional","affiliation":[{"name":"1Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Osl","sequence":"additional","affiliation":[{"name":"1Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadege","family":"Carri\u00e9","sequence":"additional","affiliation":[{"name":"5Cancer Research Center of Toulouse, INSERM, Centre National de la Recherche Scientifique, Universit\u00e9 Toulouse III-Paul Sabatier, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9353-2927","authenticated-orcid":false,"given":"Sahar","family":"Kassem","sequence":"additional","affiliation":[{"name":"5Cancer Research Center of Toulouse, INSERM, Centre National de la Recherche Scientifique, Universit\u00e9 Toulouse III-Paul Sabatier, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Lorenz","sequence":"additional","affiliation":[{"name":"1Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Christopeit","sequence":"additional","affiliation":[{"name":"1Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Munich, 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Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2159-2880","authenticated-orcid":false,"given":"Jan","family":"Attig","sequence":"additional","affiliation":[{"name":"4Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Kunz","sequence":"additional","affiliation":[{"name":"2Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7377-4574","authenticated-orcid":false,"given":"Floriana","family":"Cremasco","sequence":"additional","affiliation":[{"name":"2Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Zurich, 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3508-3173","authenticated-orcid":false,"given":"Felix","family":"Bormann","sequence":"additional","affiliation":[{"name":"1Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Kirstenpfad","sequence":"additional","affiliation":[{"name":"1Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5528-3197","authenticated-orcid":false,"given":"Thomas","family":"Kraft","sequence":"additional","affiliation":[{"name":"1Discovery Oncology, Roche Pharma Research and Early Development, Roche Innovation Center, Munich, 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