Phase 2, open-label, 1:1 randomized controlled trial exploring the efficacy of EMD 1201081 in combination with cetuximab in second-line cetuximab-naïve patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

Abstract

AIM:

To determine whether EMD 1201081, a TLR9 agonist, added to cetuximab had antitumor activity in second-line recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

METHODS:

This was a phase 2, open-label, randomized trial of EMD 1201081 0.32 mg/kg subcutaneously weekly plus cetuximab (combination) vs cetuximab monotherapy (control) in cetuximab-naïve patients with R/M SCCHN who progressed on 1 cytotoxic regimen. Crossover to combination was permitted after progression.

RESULTS:

Objective response rate in both arms was 5.7% (95% CI 1.2-15.7%) by independent assessment. Disease control was 37.7% for patients on combination (24.8-52.1%) and 43.4% on control (29.8-57.7%). Neither independent nor investigator assessments showed significant differences between study arms. Median progression-free survival was 1.5 months (1.3-2.6) for patients on combination, and 1.9 months (1.5-2.9) on control. The most frequent adverse events in the combination arm were rash (29.6%), acneiform dermatitis (22.2%), and injection site reactions (20.4%). Grade 3/4 dyspnea and hypokalemia were more frequent with cetuximab monotherapy (7.5% and 5.7% vs 1.9% each, respectively), and grade 3/4 respiratory failure and disease progression were more frequent with combination (5.6% each vs 1.9% each).

CONCLUSION:

EMD 1201081 was well tolerated combined with cetuximab, but there was no incremental clinical efficacy.

• Authors: A Ruzsa, M Sen, M Evans, L W Lee, K Hideghety, S Rottey, P Klimak, P Holeckova, J Fayette, T Csoszi, J Erfan, U Forssmann, T Goddemeier, A Bexon, C Nutting, NA EMD 1201081 Study Group
• Journal: Investigational new drugs (Invest New Drugs) Vol. 32 Issue 6 Pg. 1278-84 (Dec 2014) ISSN: 1573-0646 [Electronic] United States
• PMID: 24894651 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• IMO-2055
• Oligonucleotides
• Cetuximab

Topics

• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carcinoma, Squamous Cell (drug therapy)
• Cetuximab
• Disease-Free Survival
• Female
• Head and Neck Neoplasms (drug therapy)
• Humans
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Oligonucleotides (administration & dosage, adverse effects)
• Response Evaluation Criteria in Solid Tumors
• Squamous Cell Carcinoma of Head and Neck