Abstract CT051: From preclinical models to first-in-human evaluation of STC-1010 immunotherapy in unresectable advanced colorectal cancer

Abstract Background: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer death. It comprises two biological subtypes: microsatellite-stable (MSS, 85-95%) and microsatellite-instable (MSI-H) tumors. While MSI-H tumors respond to immunotherapy, MSS tumors remain “cold” and rely on chemotherapy. STC-1010 is a first-in-class, allogeneic antigen-induced immunotherapy derived from the Stimulated Ghost Cells (SGC) platform. SGC are produced by applying controlled physical or chemical stress to CRC cell lines, followed by haptenation to boost immune recognition; the cells are then inactivated. BreAK CRC 001 is a first-in-human trial evaluating STC-1010 with standard chemotherapy in unresectable advanced CRC. This study aims to translate preclinical findings into the clinical setting by evaluating the immunogenicity and antitumor activity of STC-1010 in combination with chemotherapy. Methods: Multi-omics analyses were performed to identify STC-1010 antigens relevance to CRC heterogeneity. The anti-tumor activity of a murine surrogate was evaluated in syngeneic CRC models. Mechanistic studies were conducted ex vivo to evaluate STC-1010-primed CD8⁺ T cells killing potency against CRC cell lines. BreAK CRC 001 is a first-in-human, open-label phase I/IIa study of STC-1010 combined with low-dose of cyclophosphamide, GM-CSF (STC-1010 regimen), and associated to standard chemotherapy for unresectable locally advanced or metastatic CRC. Phase I evaluated safety, dose-limiting toxicities, and recommended phase II dose (RP2D); phase IIa will assess safety, clinical activity and immune responses. Results: STC-1010 provides a broad repertoire of immunogenic antigens capturing CRC heterogeneity. In murine models, mSTC-1010 reduced tumor burden, improved survival, and, when combined with FOLFOX chemotherapy, significantly decreased tumor volumes compared with control. These effects were associated with increased CD8⁺ T cell infiltration. Ex vivo, CD8⁺ T cells primed by STC-1010-treated dendritic cells induced robust apoptosis in multiple CRC cell lines (HCT116, HT29, SW620). As of January 2026, 6 patients with unresectable metastatic CRC received STC-1010 regimen with SOC chemotherapy in the phase I dose-escalation part. Treatment was well tolerated, with predominantly grade 1 infusion-related reactions and no dose-limiting toxicities at the first two dose levels. Despite variable treatment duration, preliminary clinical activity was observed, including partial responses and stable disease per RECIST v1.1. Conclusion: STC-1010 regimen restores anti-tumor immunity and enhances immune cell activation in CRC models, supporting its continued clinical development. Combined with chemotherapy, it showed a manageable safety profile and early signs of clinical activity, consistent with the antitumor effects observed in preclinical models. Citation Format: Diego Tosi, Antoine Italiano, Antoine Hollebecque, Benoît You, Philippe Cassier, Francesco Sclafani, David Tougeron, Eric Christenson, Céline Gongora, Iseulys Richert, George Alzeeb, Paul Marteau, Marion Brun, Leila Feki, Lionel Chalus, Benoit Pinteur, Paul Bravetti, Sarah Kerbouche, Corinne Tortorelli, François Ghiringhelli. From preclinical models to first-in-human evaluation of STC-1010 immunotherapy in unresectable advanced colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT051.