{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:21:37Z","timestamp":1784557297472,"version":"3.55.0"},"reference-count":32,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"unspecified","delay-in-days":19,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031787","name":"Immunocore","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100031787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,7,7]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      IMC-C103C is an ImmTAC bispecific (MAGE-A4\u00d7CD3) T cell engager targeting a peptide from the cancer-testis antigen MAGE-A4 presented by HLA-A*02:01. This phase 1\/2 study in advanced solid tumors (IMC-C103C-101;\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03973333\">NCT03973333<\/jats:ext-link>\n                      ) investigated the safety and preliminary anti-tumor activity of IMC-C103C.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      HLA-A*02:01\n                      <jats:sup>+<\/jats:sup>\n                      patients with previously treated advanced solid tumors received IMC-C103C by weekly intravenous infusion, with step-up dosing introduced at higher dose levels. Dose-escalation decisions were guided by the mTPI-2 method. Key objectives included evaluating safety and preliminary anti-tumor activity; pharmacokinetics, pharmacodynamics, and biomarkers were also assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      68 patients were enrolled in 10 dose-escalation cohorts (n=56; 64% ovarian carcinoma (OC)) and one OC expansion cohort (n=12). In dose escalation, patients received doses ranging from 0.5 to 240\u2009\u00b5g. The dose-limiting toxicity rate at the two highest dose levels (1\/6 and 2\/10) did not exceed the maximum tolerated dose. A lower-dose regimen of 15\u201345-140 \u00b5g, with clinical activity, and a more favorable tolerability profile, was selected as the expansion dose. There were no treatment-related discontinuations or deaths. The most common treatment-related adverse events were cytokine-mediated, including grade 1\/2 cytokine release syndrome and associated symptoms. While MAGE-A4 expression was observed in most patient\u2019s tumors (71% positive), the level of expression was low (median H-score=16). Initial clinical and pharmacodynamic activity was observed at doses of 15 \u00b5g, with more consistent activity observed at doses \u226590\u2009\u00b5g. At doses \u226590\u2009\u00b5g, patients with MAGE-A4\n                      <jats:sup>+<\/jats:sup>\n                      OC had deeper reductions in tumor size and circulating tumor DNA and trended to have longer overall survival than patients with MAGE-A4\n                      <jats:sup>\u2013<\/jats:sup>\n                      OC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      IMC-C103C was well tolerated at doses up to 140 \u00b5g, induced dose-dependent pharmacodynamic changes, and demonstrated clinical activity in multiple patients with MAGE-A4\n                      <jats:sup>+<\/jats:sup>\n                      solid tumors. Clinical activity was dependent on MAGE-A4 expression; however, expression was especially low in the higher dosing cohorts, limiting adequate efficacy assessment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03973333\">NCT03973333<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-014638","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:00:25Z","timestamp":1784556025000},"page":"e014638","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Phase 1\/2 study of IMC-C103C, a T cell receptor bispecific (MAGE-A4\u00d7CD3) ImmTAC targeting MAGE-A4-expressing malignancies"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct03973333","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03973333","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04262466","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03973333","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Randy F","family":"Sweis","sequence":"first","affiliation":[{"name":"The University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1360-348X","authenticated-orcid":false,"given":"Ignacio","family":"Melero","sequence":"additional","affiliation":[{"name":"Clinica Universidad Navarra, CIMA and CIBERONC, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7846-8055","authenticated-orcid":false,"given":"Diwakar","family":"Davar","sequence":"additional","affiliation":[{"name":"UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Garralda","sequence":"additional","affiliation":[{"name":"Hospital Universitario Vall d\u2019Hebron, Vall d\u2019Hebron Institute of oncology (VHIO), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omid","family":"Hamid","sequence":"additional","affiliation":[{"name":"The Angeles Clinical and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Amy","family":"Chen","sequence":"additional","affiliation":[{"name":"University of California Davis Comprehensive Cancer Center, Sacramento, California, 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