Abstract LB405: BTN1A1 and YAP1 expression as biomarkers in colon cancer: Phase 1b trial results of hSTC810

Abstract Background: Butyrophilin 1A1 (BTN1A1) is a novel immune checkpoint protein expressed onvarious human tumors and immune cells. BTN1A1 has been shown to interact with Yes-associated protein 1 (YAP1), a key regulator of the Hippo pathway, which is involved in tumor growth, immune evasion, and chemoresistance. High BTN1A1 and nuclear YAP1 expression levels have been observed in colon cancer, highlighting their potential as therapeutic targets. This Phase 1b clinical trial investigates the safety, pharmacokinetics, and efficacy of the anti-BTN1A1 antibody (hSTC810) in patients with advanced colon cancer. Recently, a Phase 1clinical trial of Nelmastobart, a BTN1A1-targeting antibody, was successfully completed. The subsequent Phase 1b/2 trial investigating BTN1A1 inhibition in combination with chemotherapy is currently ongoing. Methods: Colon cancer patients were enrolled in the study and treated with hSTC810 in combination with capecitabine to evaluate the efficacy and safety of the combination therapy. A3+3 dose-escalation design was used to determine dose-limiting toxicities (DLT) and themaximum tolerated dose (MTD)/recommended Phase II dose (RP2D). Pretreatment tissue specimens were collected and analyzed for YAP1 expression to stratify patients based on YAP1 localization and intensity. The primary endpoints included safety, tolerability, and immune response markers, while the secondary endpoints included progression-free survival (PFS) and overall response rate (ORR). Tumor biopsies were also analyzed for BTN1A1 and nuclear YAP1 expression prior to treatment. Results: Among the enrolled patients, 28.57% exhibited high nuclear YAP1 expression in baseline tissue specimens, which correlated with BTN1A1 positivity. Treatment with hSTC810 demonstrated a favorable safety profile, with the most common adverse events being low-grade fatigue and infusion-related reactions. Early signs of efficacy included tumor size reductions in 42.86% (data pending analysis) of evaluable patients. Notably, patients with high YAP1expression demonstrated better PFS compared to those with low YAP1 expression. Conclusions: Findings from this Phase 1b trial suggest that targeting BTN1A1 with hSTC810 is a safe and promising therapeutic strategy for colon cancer, particularly in patients with highYAP1 expression. These results support further investigation in larger, randomized trials to confirm the efficacy and biomarker-driven utility of hSTC810 in colon cancer therapy. Citation Format: Bong-Ki Hong, Seung-Hoon Lee, Chunai Wu, Young-Seung Kim, Andrew H. Park, Stephen S. Yoo. BTN1A1 and YAP1 expression as biomarkers in colon cancer: Phase 1b trial results of hSTC810 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB405.