title: 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.
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.
authors.affiliation: Departments of Medicine and Otolaryngology, University of Colorado Cancer Center and Gates Center for Regenerative Medicine, Aurora, Colorado.
authors.forename: Antonio
authors.initials: A
authors.lastname: Jimeno
authors.affiliation: Departments of Medicine and Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Marshall R
authors.initials: MR
authors.lastname: Posner
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Wirth
authors.affiliation: Department of Hematology and Medical Oncology, Emory University Winship Cancer Institute, Atlanta, Georgia.
authors.forename: Nabil F
authors.initials: NF
authors.lastname: Saba
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Roger B
authors.initials: RB
authors.lastname: Cohen
authors.affiliation: Department of Medicine, Joan and Sanford I Weill Cornell Medical College of Cornell University, New York, New York.
authors.forename: Elizabeta C
authors.initials: EC
authors.lastname: Popa
authors.affiliation: Department of Medicine, Institute of Drug Development, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Athanassios
authors.initials: A
authors.lastname: Argiris
authors.affiliation: Department of Internal Medicine, Huntsman Cancer Institute, Salt Lake City, Utah.
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Grossmann
authors.affiliation: Karmanos Cancer Center, Wayne State University, Detroit, Michigan.
authors.forename: Ammar
authors.initials: A
authors.lastname: Sukari
authors.affiliation: Acceleron Pharma, Cambridge, Massachusetts.
authors.forename: Dawn
authors.initials: D
authors.lastname: Wilson
authors.affiliation: Acceleron Pharma, Cambridge, Massachusetts.
authors.forename: Xiaosha
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Acceleron Pharma, Cambridge, Massachusetts.
authors.forename: Jade
authors.initials: J
authors.lastname: Sun
authors.affiliation: Acceleron Pharma, Cambridge, Massachusetts.
authors.forename: Chad
authors.initials: C
authors.lastname: Glasser
authors.affiliation: Acceleron Pharma, Cambridge, Massachusetts.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Attie
authors.affiliation: Acceleron Pharma, Cambridge, Massachusetts.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Sherman
authors.affiliation: Acceleron Pharma, Cambridge, Massachusetts.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Pandya
authors.affiliation: Department of Hematology and Oncology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Jared
authors.initials: J
authors.lastname: Weiss
mesh_terms: D030301:Activin Receptors, Type II / Q000627:therapeutic use*; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000627:therapeutic use*; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007141:Immunoglobulin Fc Fragments; D008024:Ligands; D011993:Recombinant Fusion Proteins; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II; C000591618:ALK1-Fc fusion protein, human
keywords: activin receptor-like kinase 1 (ALK1); angiogenesis; bone morphogenetic protein 9 (BMP9); dalantercept. squamous cell carcinoma of the head and neck (SCCHN)