Background: Adoptive cellular therapy (ACT) has dramatically changed the landscape of immunotherapy; however, only a small proportion of solid tumor patients have benefited from these advances due to i) heterogeneity of tumor antigen expression, ii) tumor escape (e.g. only one target is addressed), or iii) off-target toxicities (e.g. expression of targets on normal tissues). 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 relevant tumor antigens per patient. ACTolog is a personalized, multi-targeted ACT approach in which autologous T-cell products are manufactured against the most relevant tumor target peptides for individual patients whose tumors are positive against a predefined target warehouse. Methods: This study is an open-label first-in-human phase I trial in patients with relapsed or refractory solid tumors expressing at least one target from a warehouse of 8 cancer targets. Key eligibility criteria include: HLA-A*02:01 phenotype, qPCR expression of warehouse target(s), prior established lines of therapy, RECIST v1.1 measurable lesions, and ECOG performance status 0 or 1. At baseline, patients will undergo leukapheresis to collect mononuclear cells for manufacturing of IMA101 cells. Patients will receive their last line of established therapy during the production phase of IMA101. IMA101 will be infused after a pre-conditioning regimen (lymphodepletion) followed by LD-IL2. The primary objective is to assess safety and tolerability of IMA101. Secondary endpoints include overall response rate (RECIST and irRC), PFS and OS. The translational objective is to assess the in vivo persistence and ex vivo functionality of transferred T cells in addition to evaluation of target expression in tumors. Enrollment to the study is currently ongoing. Clinical trial information: NCT02876510.