Trebananib (AMG 386) in Combination With Sunitinib in Patients With Metastatic Renal Cell Cancer: An Open-Label, Multicenter, Phase II Study.

Abstract

PURPOSE:

Trebananib, an investigational recombinant peptide-Fc fusion protein, neutralizes the receptor-ligand interaction between Tie2 and angiopoietin-1/2. This phase II study was conducted to evaluate trebananib plus sunitinib, a vascular endothelial growth factor receptor inhibitor, in patients with metastatic clear cell renal cell carcinoma.

PATIENTS AND METHODS:

Adults with metastatic renal cell carcinoma were enrolled sequentially onto two cohorts that received sunitinib 50 mg once per day for 4 weeks on and 2 weeks off and intravenous trebananib once per week at a dose of 10 mg/kg in cohort A or 15 mg/kg in cohort B. The primary end points were incidences of adverse events (AEs) and dose interruptions of sunitinib during the first 12 weeks of treatment. Secondary end points included objective response rate and progression-free survival.

RESULTS:

Eighty-five patients were enrolled: 43 in cohort A, and 42 in cohort B. During the first 12 weeks of treatment, 58% and 57% of patients in cohorts A and B, respectively, had sunitinib dose interruptions (dose decrease, withholding, or withdrawal). The most frequent AEs were diarrhea (cohort A, 74%; cohort B, 67%), mucosal inflammation (cohort A, 49%; cohort B, 60%), and hypertension (cohort A, 52%; cohort B, 45%). AEs of grade 3 or greater occurred in 58% of patients in cohort A and in 69% of patients in cohort B. The objective response rate was 58% and 63% in cohorts A and B, respectively. The median progression-free survival time was 13.9 months (95% CI, 10.4 to 19.2) and 16.3 months (95% CI, 13.1 to 21.4) in cohorts A and B, respectively. The median overall survival time was 36 months (95% CI, 25.2 to not estimable) in cohort A and was not estimable (median follow-up, 25 months) in cohort B.

CONCLUSION:

Trebananib plus sunitinib seemed to increase toxicity at the tested doses. Efficacy results suggest a potential benefit for the addition of trebananib to sunitinib.

• Authors: Michael B Atkins, Gwenaelle Gravis, Kazimierz Drosik, Tomasz Demkow, Piotr Tomczak, Shirley S Wong, M Dror Michaelson, Toni K Choueiri, Benjamin Wu, Lynn Navale, Douglas Warner, Alain Ravaud
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 30 Pg. 3431-8 (Oct 20 2015) ISSN: 1527-7755 [Electronic] United States
• PMID: 26304872 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by American Society of Clinical Oncology.

Chemical References

• Indoles
• Pyrroles
• Recombinant Fusion Proteins
• Sunitinib
• trebananib

Topics

• Administration, Oral
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, blood, pharmacokinetics, therapeutic use)
• Carcinoma, Renal Cell (blood, drug therapy, pathology)
• Cohort Studies
• Drug Administration Schedule
• Female
• Humans
• Indoles (administration & dosage, adverse effects, blood, pharmacokinetics)
• Injections, Intravenous
• Kidney Neoplasms (blood, drug therapy, pathology)
• Male
• Middle Aged
• Neoplasm Metastasis
• Pyrroles (administration & dosage, adverse effects, blood, pharmacokinetics)
• Recombinant Fusion Proteins (administration & dosage, adverse effects, blood, pharmacokinetics)
• Sunitinib