Phase I study of ERY974 in patients with glypican-3 (GPC-3)-positive advanced solid tumors
Presenter: Haruyasu Murakami, MD;PhD Session: Phase I Clinical Trials Time: 4/21/2026 9:00:00 AM → 4/21/2026 12:00:00 PM
Authors
Haruyasu Murakami 1 , Hidetoshi Hayashi 2 , Kensei Yamagushi 3 , Kei Muro 4 , Taroh Satoh 5 , Tomohiro Nishina 6 , Eisuke Ueda 7 , Chika Ogami 7 , Hitomi Takeshita 7 , Hayato Takahashi 7 , Mikiko Nakamura 7 , Mihiro Toba 7 , Yasutoshi Kuboki 8 1 Shizuoka Cancer Center, Shizuoka, Japan, 2 Kindai University Hospital, Osakasayama City, Japan, 3 The Cancer Institute Hospital of JFCR, Koto City, Tokyo, Japan, 4 Aichi Cancer Center, Nagoya, Japan, 5 The University of Osaka Hospital, Osaka, Japan, 6 National Hospital Organization Shikoku Cancer Center, Shizuoka, Japan, 7 Chugai Pharmaceutical Co. Ltd., Tokyo, Japan, 8 National Cancer Center Hospital East, Chiba, Japan
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. Table ERY974 dose (µg/kg) 0.12 (n=3) 0.24 (n=4) 0.50 (n=3) 0.80 (n=3) 0.80 + Steroid (n=6) 0.50/1.20 + Steroid a (n=3) 0.50/1.80 + Steroid a (n=4) 0.50/1.20/1.80 + Steroid a (n=4) 0.50/1.20/2.70 + Steroid a (n=4) 0.50/1.20/4.0 + Steroid a (n=4) Related AEs, n (%) b All grade 3 (100) 1 (25) 1 (33) 3 (100) 6 (100) 3 (100) 4 (100) 4 (100) 4 (100) 4 (100) Grade 3/4 c 0 1 (25) 0 2 (67) 3 (50) 2 (67) 4 (100) 3 (75) 4 (100) 4 (100) Serious 0 0 0 0 0 0 1 (25) 2 (50) 1 (25) 1 (25) AEs leading to withdrawal from any treatment 0 0 0 0 0 0 0 1 (25) 0 0 Best overall response, n (%) CR/PR 0 0 0 0 0 0 0 0 0 0 SD 0 1 (25) 0 0 3 (50) 0 1 (25) 0 1 (25) 2 (50) jRCT2031200382. Clinical cutoff: Oct 18, 2024 AE, Adverse event; CR, complete response; PR, partial response; SD, stable disease; SUD, step-up dosing. a Weekly SUD regimen. b Multiple occurrences of the same AE in a person is counted once. c No grade 5 AEs were reported.
Disclosure
H. Murakami, Chugai Other, The author received medical writing support from Nucleus Global paid for by Chugai. H. Hayashi, Chugai Other, The author received medical writing support from Nucleus Global paid for by Chugai. K. Yamagushi, Chugai Other, The author received medical writing support from Nucleus Global paid for by Chugai. K. Muro, Chugai The author received medical writing support from Nucleus Global paid for by Chugai. T. Satoh, Chugai Other, The author received medical writing support from Nucleus Global paid for by Chugai. T. Nishina, Chugai Other, The author received medical writing support from Nucleus Global paid for by Chugai. E. Ueda, Chugai Employment, Other, The author received medical writing support from Nucleus Global paid for by Chugai. C. Ogami, Chugai Employment, Other, The author received medical writing support from Nucleus Global paid for by Chugai. H. Takeshita, Chugai Employment, Other, The author received medical writing support from Nucleus Global paid for by Chugai. H. Takahashi, Chugai Employment, Other, The author received medical writing support from Nucleus Global paid for by Chugai. M. Nakamura, Chugai Employment, Other, The author received medical writing support from Nucleus Global paid for by Chugai. M. Toba, Chugai Employment, Other, The author received medical writing support from Nucleus Global paid for by Chugai. Y. Kuboki, Chugai Other, The author received medical writing support from Nucleus Global paid for by Chugai.
Cited in
Control: 9796 · Presentation Id: 12103 · Meeting 21436