Phase 1/2a Study of Rivoceranib, a Selective VEGFR-2 Angiogenesis Inhibitor, in Patients with Advanced Solid Tumors
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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).
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).
참고문헌 (14)
- Shibuya M, "Vascular endothelial growth factor(VEGF)and its receptor(VEGFR)signaling in angiogenesis : a crucial target for anti-and pro-angiogenic therapies", Genes Cancer, 2, pp.1097~1105 (2011)
- Wang X, "Molecular bases of VEGFR-2-mediated physiological function and pathological role", Front Cell Dev Biol, 8, pp.599281~ (2020)
- Niu G, "Vascular endothelial growth factor as an anti-angiogenic target for cancer therapy", Curr Drug Targets, 11, pp.1000~1017 (2010)
- Lian L, "VEGFR2 promotes tumorigenesis and metastasis in a pro-angiogenic-independent way in gastric cancer", BMC Cancer, 19, pp.183~ (2019)
- Fuchs CS, "Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma(REGARD) : an international, randomised, multicentre, placebo-controlled, phase 3 trial", Lancet, 383, pp.31~39 (2014)
- Ford HE, "Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma(COUGAR-02) : an open-label, phase 3 randomised controlled trial", Lancet Oncol, 15, pp.78~86 (2014)
- Kang JH, "Salvage chemotherapy for pretreated gastric cancer : a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone", J Clin Oncol, 30, pp.1513~1518 (2012)
- Wilke H, "Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma(RAINBOW) : a double-blind, randomised phase 3 trial", Lancet Oncol, 15, pp.1224~1235 (2014)
- "NCCN clinical practice guidelines in oncology (NCCN Guidelines). Gastric cancer (version 1.2023)" (2023)[URL]
- Li J, "Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction", J Clin Oncol, 34, pp.1448~1454 (2016)
- Kang YK, "Randomized phase III ANGEL study of rivoceranib(apatinib)+best supportive care(BSC)vs placebo+BSC in patients with advanced", metastatic gastric cancer who failed ≥ 2 prior chemotherapy regimens, 2019, pp.30, V877~V878
- Qin S, "Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma(CARES-310) : a randomised, open-label, international phase 3 study", Lancet, 402, pp.1133~1146 (2023)
- Hanna GJ, "A phase II trial of rivoceranib, an oral vascular endothelial growth factor receptor 2 inhibitor, for recurrent or metastatic adenoid cystic carcinoma", Clin Cancer Res, 29, pp.4555~4563 (2023)
- Eng C, "Phase Ib", II open-label study to evaluate the safety, tolerability, and efficacy of rivoceranib plus trifluridine, Ann Oncol, pp.2023, 34(Suppl 2)[DOI]