Yuan Ying, Deng Yanhong, Jin Yongdong, Guo Zengqing, Pan Yueyin, Wang Cunji, Wang Zhiwu, Hu Yi, Hua Dong, Meng Xiangjiao, Zhang Zhiye, Zhao Mingfang, Dong Xiaorong, Huang Dingzhi, Li Xiaoyan, Liu Lian, Sun Meili, Wang Huijuan, Wang Xiuwen, Yang Nong, Zhang Mingjun, Hu Sheng, Wu Dongde, Huang Jingjing, Zhang Sujie, Huang Mengna, Ding Kefeng
Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Signal Transduct Target Ther. 2025 Jul 25;10(1):241. doi: 10.1038/s41392-025-02315-7.
IBI351 (also known as fulzerasib or GFH925), an irreversible covalent inhibitor of KRAS, has demonstrated promising anti-tumour activity in patients with solid tumours. In this study, data were pooled from the phase I part of two clinical studies (NCT05005234 and NCT05497336), aiming to evaluate the efficacy and safety of IBI351 monotherapy in KRAS inhibitor-naïve Chinese patients with KRAS-mutated metastatic colorectal cancer (CRC). The objective response rate (ORR) was the primary endpoint. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). As of December 13, 2023, 56 patients treated with IBI351 monotherapy were included. The median duration of treatment was 7.7 months (range: 0.3-16.7). The confirmed ORR was 44.6% (95% CI: 31.3-58.5), with a DCR of 87.5% (95% CI: 75.9-94.8). With a median follow-up of 13.8 months, the median PFS was 8.1 months (95% CI: 5.5-13.8). The median OS was 17.0 months (95% CI: 12.6-not reached). Treatment-related adverse events (TRAEs) occurred in 53 patients (94.6%), with grade 3 TRAEs in 14 patients (25.0%). No grade 4 or 5 TRAEs were observed. The most common grade 3 TRAEs were anaemia (n = 4, 7.1%) and gamma-glutamyltransferase increased (n = 3, 5.4%). TRAEs led to dose interruption in 12 patients (21.4%) and dose reduction in six patients (10.7%). No TRAEs resulted in treatment discontinuation. IBI351 demonstrated encouraging clinical efficacy and a manageable safety profile in KRAS inhibitor-naïve Chinese patients with KRAS-mutated metastatic CRC.
IBI351（也称为富泽拉西布或GFH925）是一种不可逆的KRAS共价抑制剂，已在实体瘤患者中显示出有前景的抗肿瘤活性。在本研究中，汇集了两项临床研究（NCT05005234和NCT05497336）I期部分的数据，旨在评估IBI351单药治疗对未接受过KRAS抑制剂治疗的KRAS突变型转移性结直肠癌（CRC）中国患者的疗效和安全性。客观缓解率（ORR）是主要终点。次要终点包括疾病控制率（DCR）、无进展生存期（PFS）和总生存期（OS）。截至2023年12月13日，纳入了56例接受IBI351单药治疗的患者。中位治疗持续时间为7.7个月（范围：0.3 - 16.7）。确认的ORR为44.6%（95%CI：31.3 - 58.5），DCR为87.5%（95%CI：75.9 - 94.8）。中位随访13.8个月，中位PFS为8.1个月（95%CI：5.5 - 13.8）。中位OS为17.0个月（95%CI：12.6 - 未达到）。53例患者（94.6%）发生了治疗相关不良事件（TRAEs），14例患者（25.0%）发生3级TRAEs。未观察到4级或5级TRAEs。最常见的3级TRAEs是贫血（n = 4，7.1%）和γ-谷氨酰转移酶升高（n = 3，5.4%）。TRAEs导致12例患者（21.4%）剂量中断，6例患者（10.7%）剂量减少。没有TRAEs导致治疗中断。IBI351在未接受过KRAS抑制剂治疗的KRAS突变型转移性CRC中国患者中显示出令人鼓舞 的临床疗效和可控 的安全性。
