1.Phase 1/2a Study of Rivoceranib, a Selective VEGFR-2 Angiogenesis Inhibitor, in Patients with Advanced Solid Tumors
Yoon-Koo KANG ; Min-Hee RYU ; Yong Sang HONG ; Chang-Min CHOI ; Tae Won KIM ; Baek-Yeol RYOO ; Jeong Eun KIM ; John R. WEIS ; Rachel KINGSFORD ; Cheol Hee PARK ; Seong JANG ; Arlo MCGINN ; Theresa L. WERNER ; Sunil SHARMA
Cancer Research and Treatment 2024;56(3):743-750
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).
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