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

• Type of Material: Article
• Authors: Antonio Jimeno, University of Colorado; Marshall R. Posner, Icahn School of Medicine at Mount Sinai; Lori J. Wirth, Massachusetts General Hospital; Nabil Saba, Emory University; Roger B. Cohen, University of Pennsylvania; Elizabeta C. Popa, Cornell University; Athanassios Argiris, University of Texas San Antonio; Kenneth F. Grossmann, Huntsman Cancer Institute; Ammar Sukari, Wayne State University; Dawn Wilson, Acceleron Pharma; Xiaosha Zhang, Acceleron Pharma; Jade Sun, Acceleron Pharma; Chad Glasser, Acceleron Pharma; Kenneth M. Attie, Acceleron Pharma; Matthew L. Sherman, Acceleron Pharma; Susan S. Pandya, Acceleron Pharma; Jared Weiss, University of North Carolina
• Language: English
• Date: 2016-12-01
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 American Cancer Society
• Final Published Version (URL): http://dx.doi.org/10.1002/cncr.30317
• Title of Journal or Parent Work: CANCER
• Volume: 122
• Issue: 23
• Start Page: 3641
• End Page: 3649
• Grant/Funding Information: This study was supported by Acceleron Pharma.
• Keywords: bone morphogenetic protein 9 (BMP9); CANCER STATISTICS; ANGIOGENESIS; ALK1; angiogenesis; HYPONATREMIA; Oncology; INAPPROPRIATE ANTIDIURETIC-HORMONE; dalantercept. squamous cell carcinoma of the head and neck (SCCHN); activin receptor-like kinase 1 (ALK1); Science & Technology; SECRETION; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Oncology

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. © 2016 American Cancer Society.