Phase 1/2 study of IMC-C103C, a T cell receptor bispecific (MAGE-A4×CD3) ImmTAC targeting MAGE-A4-expressing malignancies

作者：Randy F. Sweis, Ignacio Melero, Diwakar Davar, Elena Garralda, Omid Hamid, Hui Amy Chen, T R J Evans, Kathleen N. Moore, Joseph J. Sacco, Fiona Thistlethwaite, Anja Williams, George R. Blumenschein, Margaret K. Callahan, Melissa L. Johnson, Erin L. Schenk, Jason Wustner, Sarah Stanhope, Kaixiang Tao, Shannon Marshall, Juanita Lopez · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2026 · DOI：10.1136/jitc-2025-014638 · 研究领域：Immunotherapy and Immune Responses、CAR-T cell therapy research、Cancer Immunotherapy and Biomarkers

Purpose IMC-C103C is an ImmTAC bispecific (MAGE-A4×CD3) 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; NCT03973333 ) investigated the safety and preliminary anti-tumor activity of IMC-C103C. Methods HLA-A*02:01 + 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. Results 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 µg. 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 15–45-140 µg, 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’s tumors (71% positive), the level of expression was low (median H-score=16...