Cancer Res Treat.  2024 Jul;56(3):743-750. 10.4143/crt.2023.980.

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

• Kang YK
• Ryu MH
• Hong YS
• Choi CM
• Kim TW
• Ryoo BY
• Kim JE
• Weis JR
• Kingsford R
• Park CH
• Jang S
• McGinn A
• Werner TL
• Sharma S

• KMID: 2557661
• DOI: http://doi.org/10.4143/crt.2023.980

Abstract

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).

Keyword

Apatinib; Rivoceranib; Stomach neoplasms; Solid tumors

Figure

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  Fig. 1. Parts 1 and 2 combined. Kaplan-Meier estimates of progression-free survival (PFS) (A) and overall survival (OS) (B) in the efficacy analysis set.

Reference

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