Phase 1/2a Study of Rivoceranib, a Selective VEGFR-2 Angiogenesis Inhibitor, in Patients with Advanced Solid Tumors

• Published in: Cancer research and treatment Vol. 56; no. 3; pp. 743 - 750
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Cancer Association 01.07.2024; 대한암학회
• Subjects: Adult; Aged; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - adverse effects; Angiogenesis Inhibitors - pharmacokinetics; Angiogenesis Inhibitors - therapeutic use; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Neoplasms - drug therapy; Neoplasms - pathology; Original; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - pharmacokinetics; Protein Kinase Inhibitors - therapeutic use; Treatment Outcome; Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors; 의학일반; Apatinib; Rivoceranib; Solid tumors; Stomach neoplasms
• ISSN: 1598-2998; 2005-9256; 2005-9256
• DOI: 10.4143/crt.2023.980

Purpose 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.Materials and Methods 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.Results 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%.Conclusion 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).