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Phase Ib trial of the Toll-like receptor 9 agonist IMO-2055 in combination with 5-fluorouracil, cisplatin, and cetuximab as first-line palliative treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck

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Machiels, Jean-Pascal [UCL] Kaminsky, Marie-Christine Keller, Ulrich Brümmendorf, Tim H Goddemeier, Thomas Delord, Jean-Pierre

BACKGROUND: This Phase Ib trial assessed the maximum tolerated dose (MTD) and safety of the Toll-like receptor 9 agonist IMO-2055 combined with 5-fluorouracil, cisplatin, and cetuximab (PFE) as first-line palliative treatment in patients with relapsed and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). METHODS: A standard 3+3 study design was used. Patients were sequentially enrolled to be treated with IMO-2055 (0.16, 0.32, or 0.48 mg/kg/day; days 1, 8, 15), 5-fluorouracil (1,000 mg/m(2)/day; days 1-4), cisplatin (100 mg/m(2)/day; day 1) and cetuximab (400 mg/m(2)/day first dose; then 250 mg/m(2)/day; days 1, 8, 15) every 3 weeks. RESULTS:Thirteen patients received IMO-2055. Dose-limiting toxicities (DLTs; ie, any Grade [G]3/4 treatment-related adverse events [TEAEs] in cycle 1) occurred in 2/4 patients treated with IMO-2055 0.32 mg/kg (G4 hypokalemia and hypomagnesemia [n=1]; G4 septicemia, hyperthermia, febrile neutropenia, and G3 hypotension [n=1]). In the IMO-2055 0.16-mg/kg expansion cohort, 1 patient experienced DLTs of G3 sepsis, bacteremia, and hyperthermia. The most common G ≥ 3 TEAEs were neutropenia (n=9; not including febrile neutropenia [n=1]), hypokalemia (n=5), and hypomagnesemia (n=4). Serious adverse events (SAEs) occurred in 8 patients, including 4 with SAEs considered IMO-2055 related; 1 of these patients died. Best response achieved overall was partial response in 3 patients and stable disease in 9 patients. The overall safety profile led to early trial termination; the safety monitoring committee did not confirm the MTD (formally IMO-2055 0.16 mg/kg). CONCLUSIONS: Regimens combining IMO-2055 and PFE cannot be recommended for further development in R/M SCCHN patients.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2013
Language Anglais
Journal information "Investigational New Drugs : the journal of new anti-cancer agents" - Vol. 31, no.5, p. 1207-1216 (2013)
Peer reviewed yes
Publisher Springer New York LLC ((United States) New York)
issn 0167-6997
e-issn 1573-0646
Publication status Publié
Affiliations UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie
UCL - (SLuc) Unité d'oncologie médicale
UCL - (SLuc) Centre du cancer
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Bibliographic reference Machiels, Jean-Pascal ; Kaminsky, Marie-Christine ; Keller, Ulrich ; Brümmendorf, Tim H ; Goddemeier, Thomas ; et. al. Phase Ib trial of the Toll-like receptor 9 agonist IMO-2055 in combination with 5-fluorouracil, cisplatin, and cetuximab as first-line palliative treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck. In: Investigational New Drugs : the journal of new anti-cancer agents, Vol. 31, no.5, p. 1207-1216 (2013)
Permanent URL http://hdl.handle.net/2078.1/140335