Background: Adoptive cellular therapy (ACT) has demonstrated substantial clinical progresses in hematologic cancers; however, only a small proportion of solid tumor patients have benefited from these advances due to i) lack of suitable immunotherapy targets with high specificity in solid tumors, ii) frequent relapse following immunotherapy to single targets often associated with loss of target expression in the tumor. The ACTolog^® concept, utilizing antigen specific T cells (IMA101) against targets identified by the Immatics’ proprietary XPRESIDENT^® technology, is intended to overcome these limitations by addressing multiple novel tumor antigens per patient. One key defining feature in this trial is the generation of robust T cells, where autologous T cells are primed against the expressed ACTolog targets in the presence of IL-21 followed by HLA tetramer-guided cell sorting and rapid expansion. This process has been shown to result in higher frequencies of central memory T cells, extended in vivo persistence, and a more robust clinical response. Methods: This study is a first-in-human phase I trial in patients with relapsed or refractory solid tumors expressing up to 4 targets from a warehouse of 8 cancer targets in which autologous T-cell products are manufactured against the most relevant tumor target peptides for individual patients. Key eligibility criteria include: HLA-A*02:01 phenotype, qPCR biomarker positive from a tumor biopsy, RECIST v1.1 measurable lesions, and ECOG status 0 or 1. At baseline, patients will undergo leukapheresis to collect mononuclear cells for manufacturing of IMA101 cells. Patients will receive anti-cancer therapy during the production phase. IMA101 will be infused after lymphodepletion regimen followed by low dose IL2. The primary objective is to assess safety and tolerability of IMA101. Secondary endpoints include overall response rate, PFS and OS. The translational objective includes the assessment of in vivo persistence and ex vivo characterization of transferred T cells in addition to evaluation of target expression in tumors. Enrollment in the study is currently ongoing. Clinical trial information: NCT02876510