A Phase I, Open-Label Study of Trebananib Combined With Sorafenib or Sunitinib in Patients With Advanced Renal Cell Carcinoma

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• 作者：David S. Hong¹ ; ^{dshong@mdanderson.org" class="auth_mail} ; Michael S. Gordon² ; Wolfram E. Samlowski³ ; Razelle Kurzrock¹ ; Nizar Tannir¹ ; David Friedland⁴ ; David S. Mendelson² ; Nicholas J. Vogelzang³ ; Erik Rasmussen⁵ ; Benjamin M. Wu⁵ ; Michael B. Bass⁵ ; Zhandong D. Zhong⁵ ; Gregory Friberg⁵ ; Leonard J. Appleman⁴
• 关键词：Angiogenesis ; Angiopoietins ; Targeted therapies ; Tie2 receptor ; Vascular growth factor receptor
• 刊名：Clinical Genitourinary Cancer
• 出版年：June 2014
• 年：2014
• 卷：12
• 期：3
• 页码：167-177.e2
• 全文大小：1428 K

文摘

Trebananib, an investigational peptibody, binds to angiopoietin 1 and 2, thereby blocking their interaction with Tie2.

Patients and Methods

This open-label phase I study examined trebananib 3 mg/kg or 10 mg/kg intravenous (I.V.) once weekly plus sorafenib 400 mg twice per day or sunitinib 50 mg once per day in advanced RCC. Primary end points were adverse event incidence and pharmacokinetics.

Results

Thirty-seven patients were enrolled. During trebananib plus sorafenib administration (n = 17), the most common treatment-related adverse events (TRAEs) included rash (n = 12; 71%), diarrhea (n = 12; 71%), hypertension (n = 11; 65%), and fatigue (n = 11; 65%); grade ≥ 3 TRAEs (n = 7; 41%); and 2 patients (12%) had peripheral edema. During trebananib plus sunitinib administration (n = 19), the most common TRAEs included diarrhea (n = 14; 74%), fatigue (n = 13; 68%), hypertension (n = 11; 58%), and decreased appetite (n = 11; 58%); grade ≥ 3 TRAEs (n = 13; 68%); and 8 (42%) patients had peripheral edema. Trebananib did not appear to alter the pharmacokinetics of sorafenib or sunitinib. No patient developed anti-trebananib antibodies. Objective response rates were 29% (trebananib plus sorafenib) and 53% (trebananib plus sunitinib).

Conclusion

The toxicities of trebananib 3 mg/kg or 10 mg/kg I.V. plus sorafenib or sunitinib in RCC were similar to those of sorafenib or sunitinib monotherapy, with peripheral edema being likely specific to the combinations. Antitumor activity was observed.