Kang Yoon-Koo, Ryu Min-Hee, Hong Yong Sang, Choi Chang-Min, Kim Tae Won, Ryoo Baek-Yeol, Kim Jeong Eun, Weis John R, Kingsford Rachel, Park Cheol Hee, Jang Seong, McGinn Arlo, Werner Theresa L, Sharma Sunil
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
University of Utah and Huntsman Cancer Institute, Salt Lake City, UT, USA.
Cancer Res Treat. 2024 Jul;56(3):743-750. doi: 10.4143/crt.2023.980. Epub 2024 Jan 18.
This study aimed to report the results from an early-phase study of rivoceranib, an oral tyrosine kinase inhibitor highly selective for vascular endothelial growth factor receptor 2, in patients with advanced solid tumors.
In this open-label, single-arm, dose-escalating, multicenter three-part phase 1/2a trial, patients had advanced solid tumors refractory to conventional therapy. Part 1 evaluated the safety and pharmacokinetics of five ascending once-daily doses of rivoceranib from 81 mg to 685 mg. Part 2 evaluated the safety and antitumor activity of once-daily rivoceranib 685 mg. Part 3 was conducted later, due to lack of maximum tolerated dose determination in part 1, to evaluate the safety and preliminary efficacy of once-daily rivoceranib 805 mg in patients with unresectable or advanced gastric cancer.
A total of 61 patients were enrolled in parts 1 (n=25), 2 (n=30), and 3 (n=6). In parts 1 and 2, patients were white (45.5%) or Asian (54.5%), and 65.6% were male. The most common grade ≥ 3 adverse events were hypertension (32.7%), hyponatremia (10.9%), and hypophosphatemia (10.9%). The objective response rate (ORR) was 15.2%. In part 3, dose-limiting toxicities occurred in two out of six patients: grade 3 febrile neutropenia decreased appetite, and fatigue. The ORR was 33%.
The recommended phase 2 dose of rivoceranib was determined to be 685 mg once daily, which showed adequate efficacy with a manageable safety profile (NCT01497704 and NCT02711969).
本研究旨在报告口服酪氨酸激酶抑制剂瑞沃西尼（对血管内皮生长因子受体2具有高度选择性）在晚期实体瘤患者中的一项早期研究结果。
在这项开放标签、单臂、剂量递增的多中心三部分1/2a期试验中，患者患有对传统治疗难治的晚期实体瘤。第1部分评估了瑞沃西尼每日一次、剂量从81毫克递增至685毫克的五个剂量水平的安全性和药代动力学。第2部分评估了瑞沃西尼每日一次685毫克的安全性和抗肿瘤活性。由于第1部分未确定最大耐受剂量，第3部分随后开展，以评估瑞沃西尼每日一次805毫克在不可切除或晚期胃癌患者中的安全性和初步疗效。
第1部分（n = 25）、第2部分（n = 30）和第3部分（n = 6）共纳入61例患者。在第1部分和第2部分，患者为白人（45.5%）或亚洲人（54.5%），65.6%为男性。最常见的≥3级不良事件为高血压（32.7%）、低钠血症（10.9%）和低磷血症（10.9%）。客观缓解率（ORR）为15.2%。在第3部分，6例患者中有2例出现剂量限制性毒性：3级发热性中性粒细胞减少、食欲减退和疲劳。ORR为33%。结论：瑞沃西尼的推荐2期剂量确定为每日一次685毫克，其显示出足够的疗效且安全性可控（NCT01497704和NCT02711969）。
