Safety and efficacy results from the phase I/IIa study of FG-M108 plus CAPOX as first-line (1L) treatment for patients with CLDN18.2+/HER2- locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.

person Funan Liu Phase I Clinical Trials Center, The First Hospital of China Medical University, Shenyang, China info_outline Funan Liu, Jifang Gong, Zhaoyu Jin, Miao Zhang, Shu Zhang, Yanqiao Zhang, Xinjun Liang, Yun Li, Xiaochun Yang, Yaping Yang, Lin Shen

Authors person Funan Liu Phase I Clinical Trials Center, The First Hospital of China Medical University, Shenyang, China info_outline Funan Liu, Jifang Gong, Zhaoyu Jin, Miao Zhang, Shu Zhang, Yanqiao Zhang, Xinjun Liang, Yun Li, Xiaochun Yang, Yaping Yang, Lin Shen Organizations Phase I Clinical Trials Center, The First Hospital of China Medical University, Shenyang, China, Department of Gastrooncology, Beijing Cancer Hospital, Beijing, China, FutureGen Biopharmaceutical (Beijing) Co, Beijing, Beijing, China, Peking University Cancer Hospital and Institute, Beijing, China, Shandong Cancer Hospital and Institute, Jinan, China, Harbin Medical University Cancer Hospital, Harbin, China, Hubei Cancer Hospital, Wuhan, China, Futuregen Biopharmaceutical (Beijing) Co., Ltd, Beijing, China, FutureGen Biopharmaceutical (Beijing) Co., Beijing, China Abstract Disclosures Research Funding Funding Source: FutureGen Biopharmaceutical (Beijing) Co., Ltd Background: There is an unmet medical need for 1L treatment of patients with HER2- G/GEJ adenocarcinoma. CLDN18.2 is expressed in normal gastric mucosa cells and retained in G/GEJ tumor cells. FG-M108 is a monoclonal antibody specifically targeting CLDN18.2 with optimal affinity and enhanced antibody-dependent cellular cytotoxicity. FG-M108 has demonstrated potent anti-tumor activity and excellent safety profile in preclinical studies. Methods: This cohort of a phase I/IIa study evaluated the safety and preliminary efficacy of FG-M108 300 mg/m 2 every 3 weeks plus CAPOX in patients with locally advanced unresectable or metastatic G/GEJ adenocarcinoma. Patients had measurable lesions and were HER2- and CLDN18.2+ (immunohistochemistry [IHC] 1+/2+/3+≥10%). At baseline, 22 patients (43.1%) had liver metastases and 15 (29.4%) had peritoneal metastases. Treatment-emergent adverse events (TEAEs) were categorized by CTCAE v5.0. Efficacy was evaluated every 6 weeks per RECIST1.1. Results: As of January 12, 2024, 52 patients were treated. Most TEAEs were grade 1-2; grade ≥3 TEAEs occurred in 55.8% of patients and serious TEAEs in 25.0%. The most common TEAEs were neutropenia (63.5%), thrombocytopenia (44.2%), and hypoalbuminemia (42.3%). FG-M108–related grade ≥3 TEAEs occurred in 36.5% of patients and FG-M108–related serious TEAEs in 11.5%. No FG-M108–related grade 4-5 TEAEs were reported. No patients withdrew due to severe nausea, vomiting or hypoalbuminemia during the treatment period. Confirmed objective response rate (ORR) and disease control rate (DCR) were 46.7% (7/15) and 100.0% (15/15), respectively, in 15 patients with low CLDN18.2 expressions (IHC 1+/2+/3+ ≥10% & 2+/3+ <40%). Median progression-free survival (mPFS) in patients with low CLDN18.2 expressions was 5.0 months, similar to treatment effect of CAPOX. For 36 patients with medium or high expressions of CLDN18.2 (IHC 2+/3+ ≥40%), confirmed ORR was 77.8% (28/36) and DCR was 97.2% (35/36). The median follow-up was 218 days, and mPFS and median duration of response (mDOR) have not been reached yet; However, FG-M108 plus CAPOX have shown a clear trend to prolong the PFS and DOR in this group as compared to patients with low CLDN18.2 expressions (estimated HR=0.33). Median overall survival has not been reached. Conclusions: FG-M108 plus CAPOX as 1L treatment for CLDN18.2+/HER2- advanced G/GEJ cancer showed good tolerability and improved efficacy compared to historical CAPOX control, with an apparent trend of better efficacy with higher CLDN18.2 expression. Based on these results, pivotal phase 3 study of FG-M108 plus CAPOX versus CAPOX as 1L treatment of locally advanced unresectable or metastatic G/GEJ adenocarcinoma expressing medium/high CLDN18.2 has been initiated and is ongoing. Clinical trial information: NCT06177041 .