Abstract CT197: Phase I study of ERY974 in patients with glypican-3 (GPC-3)-positive advanced solid tumors

Abstract Background: ERY974, a bispecific antibody targeting GPC3 and CD3, redirects T cells to GPC3+ tumors to enhance immune responses. GPC3 is highly expressed in solid tumors and minimally present in normal tissue, making it a promising target. ERY102JP (Phase I) evaluated ERY974 in patients (pts) with GPC3+ advanced/recurrent solid tumors. A prior study showed limited tolerability at doses ≥0.81 µg/kg due to cytokine release syndrome (CRS), prompting investigation of prophylactic strategies. Methods: Eligible pts had tumors with ≥1% GPC3 expression. Pts got ERY974 (0.12-4.0 µg/kg; dose escalation design) by IV once weekly (QW). Tocilizumab (toc), an IL-6 receptor antagonist, was given before ERY974 (all cohorts) to mitigate CRS. Steroids (Cohorts 5-10) and step-up dosing (SUD; Cohorts 6-10) were added to reduce CRS and hepatotoxicity. Endpoints included safety, PK and anti-tumor activity (RECIST 1.1). Results: 38 pts were enrolled across 10 cohorts. Grade ≥3 adverse events (AEs) occurred in 61% (23/38) of pts; ALT increased was seen in 37% (14/38) and AST increased in 24% (9/38). Dose-limiting toxicities occurred in 1 of 3 pts in the 0.80 µg/kg QW cohort, 1 of 6 pts in 0.80 µg/kg QW + Steroid cohort, and 3 of 4 pts in 0.5/1.2/4.0 µg/kg QW + Steroid cohort. The maximum tolerated dose was 2.7 µg/kg. No responses were seen (Table). ERY974 exposure increased dose-dependently; higher exposure, including 4.0 µg/kg, was achieved using SUD with steroids. CRS occurred in 55% (21/38) of pts, most often in cohorts receiving ERY974 ≥0.80 µg/kg. CRS incidence was 0% at 0.24 µg/kg with toc alone, and lower at initial ERY974 dose of 0.50 µg/kg with steroids (33%) vs without (67%). Higher ERY974 plasma concentrations were associated with increased risk of CRS (p=0.01) and grade ≥3 liver toxicity (p=0.05). Conclusions: Use of SUD, steroid premedication and toc enabled escalation to higher ERY974 doses (up to 2.7 µg/kg was tolerated) with manageable safety profiles. Toc likely mitigated CRS. Anti-tumor activity was limited. Citation Format: Haruyasu Murakami, Hidetoshi Hayashi, Kensei Yamagushi, Kei Muro, Taroh Satoh, Tomohiro Nishina, Eisuke Ueda, Chika Ogami, Hitomi Takeshita, Hayato Takahashi, Mikiko Nakamura, Mihiro Toba, Yasutoshi Kuboki. Phase I study of ERY974 in patients with glypican-3 (GPC-3)-positive advanced solid tumors [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 CT197.