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: 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
• Journal: Cancer (Cancer) Vol. 122 Issue 23 Pg. 3641-3649 (Dec 01 2016) ISSN: 1097-0142 [Electronic] United States
• PMID: 27648727 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: © 2016 American Cancer Society.

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents
• Immunoglobulin Fc Fragments
• Ligands
• Recombinant Fusion Proteins
• ACVRL1 protein, human
• Activin Receptors, Type II
• ALK1-Fc fusion protein, human

Topics

• Activin Receptors, Type II (therapeutic use)
• Aged
• Angiogenesis Inhibitors (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Squamous Cell (drug therapy)
• Disease-Free Survival
• Female
• Head and Neck Neoplasms (drug therapy)
• Humans
• Immunoglobulin Fc Fragments (therapeutic use)
• Ligands
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Neovascularization, Pathologic (drug therapy)
• Recombinant Fusion Proteins (therapeutic use)
• Squamous Cell Carcinoma of Head and Neck
• Treatment Outcome