Abstract 91P
Background
Soft tissue sarcomas (STS) and osteosarcoma (OS) represent significant challenges in cancer therapy, often associated with poor prognosis. Treatment options are mainly limited to conventional chemotherapy and surgery, lacking effective targeted approaches. The leucine-rich repeat-containing protein 15 (LRRC15) has emerged as a promising target due to its overexpression in several sarcoma subtypes. SOT106 is currently being developed as an LRRC15-targeted antibody-drug conjugate (ADC) with monomethyl auristatin E (MMAE) using a platform engineered for tumor-specific payload release.
Methods
Immunohistochemistry (IHC) analysis was conducted on tissue microarrays (TMAs) to evaluate LRRC15 expression across bone cancer and STS samples, utilizing a proprietary diagnostic antibody. This antibody was designed to support prospective patient selection in clinical trials. Target expression was assessed in 51 pediatric and 37 adult OS samples, as well as in chondrosarcoma and multiple STS subtypes, including undifferentiated pleomorphic sarcoma (UPS), leiomyosarcoma, and rhabdomyosarcoma. In vivo efficacy studies in patient-derived xenograft (PDX) models were conducted in several STS models and pediatric OS models with moderate to high LRRC15 expression.
Results
Our analysis revealed the highest tumor expression of LRRC15 in OS, with 77% of adult patients and 59% of pediatric patients exhibiting ≥10% LRRC15+ cells. In chondrosarcoma, LRRC15 expression was observed in 58% of cases (n=38). Among STS, LRRC15 expression was identified in UPS (41%, n=79), leiomyosarcoma (40%, n=30), and rhabdomyosarcoma (30%, n=23). SOT106 demonstrated strong antitumor activity in variety of STS and OS PDX models outperforming clinical benchmark across several parameters.
Conclusions
Our findings, showing the high prevalence of LRRC15 expression in sarcomas and the antitumor potency of SOT106 in preclinical models, strongly support its clinical development as a novel therapy for treating STS and OS, including pediatric cases. Combined with its superior performance over clinical benchmark, these results underscore the potential of SOT106 as a best-in-class targeted treatment for these challenging malignancies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
SOTIO Biotech a.s.
Funding
SOTIO Biotech a.s.
Disclosure
M. Fojtů, F. Jaburek, I. Valentova, A. Ranger, A. Jensen-Smith, I. Adkins, L. Palová Jelínková, U. Moebius, M. Steegmaier, R. Spisek: Financial Interests, Personal, Full or part-time Employment: SOTIO Biotech a.s.