Data from Patritumab with Cetuximab plus Platinum-Containing Therapy in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: An Open-Label, Phase Ib Study

Abstract

<div>AbstractPurpose:<p>Patritumab plus cetuximab with platinum as first-line therapy for patients with recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) was evaluated for safety and to determine the recommended phase II combination dose.</p>Patients and Methods:<p>Patients aged ≥18 years with confirmed R/M SCCHN received intravenous patritumab (18 mg/kg loading dose; 9 mg/kg maintenance dose every 3 weeks) + cetuximab (400 mg/m<sup>2</sup> loading dose; 250 mg/m<sup>2</sup> maintenance dose weekly) + cisplatin (100 mg/m<sup>2</sup> every 3 weeks) or carboplatin (AUC of 5) for six cycles or until toxicity, disease progression, or withdrawal. Primary endpoints were dose-limiting toxicities [DLT; grade ≥3 (21-day observation period)] and treatment-emergent adverse events (TEAE). Pharmacokinetics, human antihuman antibodies (HAHA), tumor response, progression-free survival (PFS), and overall survival (OS) were assessed.</p>Results:<p>Fifteen patients completed a median (range) of 8.7 (2.0–20.7) patritumab cycles. No DLTs were reported. Serious adverse events were reported in 9 patients (patritumab-related <i>n</i> = 4). TEAEs (<i>N</i> = 15 patients) led to patritumab interruption in 7 patients. Patritumab-related dose reductions were reported in 1 patient. Patritumab (18 mg/kg) pharmacokinetics (<i>N</i> = 15) showed mean (SD) AUC<sub>0–21d</sub> of 2,619 (560) μg/day/mL and maximum concentration of 499.9 (90.4) μg/mL. All patients were HAHA-negative at study end (single, transient low titer in 1 patient). Tumor response rate (complete plus partial response; <i>N</i> = 15) was 47%. Median (95% confidence interval) PFS and OS (<i>N</i> = 15) were 7.9 (3.7–9.7) and 13.5 (6.6–17.5) months, respectively.</p>Conclusions:<p>Patritumab (18 mg/kg loading dose, 9 mg/kg maintenance dose) plus cetuximab/platinum was tolerable, active in SCCHN, and selected as the phase II dose regimen.</p></div>