Abstract A061: First-in-human hapten-enhanced stressed-ghost cell immunotherapy (STC-1010) for advanced colorectal cancer: preclinical and early clinical data

Abstract Background Colorectal cancer (CRC) remains the second leading cause of cancer-related mortality worldwide, and most patients derive limited benefit from current immunotherapies. To increase tumor immunogenicity, we developed a next-generation in vivo immunotherapy platform based on Stimulated Ghost Cells (SGC), generated by controlled physical or chemical stress and hapten-induced immune flare. STC-1010 is a human allogeneic SGC-derived product consisting of three CRC cell lines stressed to mimic resistant phenotypes, haptenated to enhance immunogenicity, and rendered non-proliferative (ghost). Methods The immunobiological properties of STC-1010 were assessed in preclinical and clinical settings. Ex vivo, dendritic cells were exposed to STC-1010 analyzed for gene-expression analysis and detection of haptenated epitopes, then co-cultured with CD8+ T cells to evaluate T-cell activation and tumor cell apoptosis; combination with anti-CTLA-4 was also examined. In vivo, a murine surrogate SGC product was used to characterize anti-tumor activity and immunomodulatory effects. Based on these findings, the first-in-human BreAK CRC 001 phase I/IIa trial was launched in patients with unresectable, metastatic, or locally advanced CRC (NCT06934538). This multicenter study includes a phase I dose-escalation and expansion followed by a phase IIa cohort expansion. Phase I assesses the safety of STC-1010 combined with immunostimulant (IS) and standard-of-care, aiming to establish the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Phase IIa evaluates preliminary efficacy. Results Murine proof-of-concept studies using the SGC surrogate demonstrated in vivo anti-tumor efficacy and modulation of tumor-draining lymph nodes, notably within B-cell compartments. Ex vivo, STC-1010-conditioned DCs upregulated genes involved in antigen processing and presentation, and haptenated epitopes were detected on mature DCs, confirming efficient uptake and processing. Functionally, STC-1010-primed DCs enhanced CD8+ T-cell activation and induced tumor cell apoptosis. Combining STC-1010 with anti-CTLA-4 further increased tumor cell apoptosis, suggesting a synergistic effect. As of the current data cutoff, three patients have been treated with first-line SOC mFOLFOX6 combined with STC-1010. STC-1010 has been well tolerated, with no treatment-related adverse events observed, and the safety profile has been consistent with SOC chemotherapy. Early clinical observations following completion of the 8 induction injections and 1-month boost show encouraging signs of activity, with two patients achieving a partial response and one patient stable disease per RECIST. Ongoing translational analyses will further characterize immunological and clinical responses. Conclusion STC-1010 shows strong immunogenicity in preclinical models with potential synergy with anti-CTLA-4. Early clinical data indicate a favorable safety profile and initial signs of activity. Ongoing enrollment and correlative analyses will establish the RP2D and descrive the immunological response. Citation Format: George Alzeeb, Iseulys Richert, Paul Marteau, Lionel Chalus, Marion Brun, Benoit Pinteur, Paul Bravetti, Corinne Tortorelli, Diego Tosi, François Ghiringhelli, Antoine Italiano. First-in-human hapten-enhanced stressed-ghost cell immunotherapy (STC-1010) for advanced colorectal cancer: preclinical and early clinical data [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr A061.