A phase 2 study of dalantercept, an activin receptor-like kinase-1 ligand trap, in patients with recurrent or metastatic squamous cell carcinoma of the head and neck

Antonio Jimeno, Marshall R. Posner, Lori J. Wirth, Nabil F. Saba, Roger B. Cohen, Elizabeta C. Popa, Athanassios Argiris, Kenneth F. Grossmann, Ammar Sukari, Dawn Wilson, Xiaosha Zhang, Jade Sun, Chad Glasser, Kenneth M. Attie, Matthew L. Sherman, Susan S. Pandya, Jared Weiss

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

BACKGROUND: Patients with platinum-refractory, recurrent or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN) have limited options. Activin receptor-like kinase 1 (ALK1) is a type I receptor of the transforming growth factor β superfamily expressed on activated endothelial cells. Dalantercept is an ALK1 receptor fusion protein that acts as a ligand trap to block signaling through ALK1 and inhibits stages of angiogenesis involved in blood vessel maturation and stabilization. In a phase 1 study, dalantercept demonstrated clinical activity in patients with RM-SCCHN. The objective of the current study was to evaluate the activity of dalantercept in RM-SCCHN. METHODS: Forty-six patients received dalantercept at doses of 80 mg (n = 2), 0.6 mg/kg (n = 13), or 1.2 mg/kg (n = 31) subcutaneously every 3 weeks. The primary endpoint was the overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). Secondary endpoints included progression-free survival and overall survival, safety and tolerability, and pharmacokinetic and pharmacodynamic assessments. RESULTS: Forty patients were evaluable for response (13 who received dalantercept 0.6 mg/kg and 27 who received dalantercept 1.2 mg/kg). The overall response rate was 5% (n = 2), and 35% of patients had stable disease; 44% of patients who received 1.2 mg/kg and 30.8% of those who received 0.6 mg/kg achieved disease control (partial response or stable disease). The median progression-fee survival was 1.4 months (95% confidence interval, 1.3-2.2 months), and the median overall survival was 7.1 months (95% confidence interval, 5.5-11.1 months). Drug-related adverse events (>15%) were anemia, fatigue, peripheral edema, headache, and hyponatremia. CONCLUSIONS: In an unselected, heavily pretreated population of patients with RM-SCCHN, dalantercept monotherapy resulted in a favorable safety profile but only modest dose-dependent activity, and it did not meet the primary efficacy objective of the study. Cancer 2016;122:3641-9.

Original languageEnglish (US)
Pages (from-to)3641-3649
Number of pages9
JournalCancer
Volume122
Issue number23
DOIs
StatePublished - Dec 1 2016

Keywords

  • activin receptor-like kinase 1 (ALK1)
  • angiogenesis
  • bone morphogenetic protein 9 (BMP9)
  • dalantercept. squamous cell carcinoma of the head and neck (SCCHN)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Jimeno, A., Posner, M. R., Wirth, L. J., Saba, N. F., Cohen, R. B., Popa, E. C., Argiris, A., Grossmann, K. F., Sukari, A., Wilson, D., Zhang, X., Sun, J., Glasser, C., Attie, K. M., Sherman, M. L., Pandya, S. S., & Weiss, J. (2016). A phase 2 study of dalantercept, an activin receptor-like kinase-1 ligand trap, in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Cancer, 122(23), 3641-3649. https://doi.org/10.1002/cncr.30317