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

Background: 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. Methods: Patients aged ≥18 years with confirmed R/M SCCHN received intravenous patritumab (18-mg/kg loading dose [LD]); 9-mg/kg maintenance dose [MD] every 3 weeks [q3w]) + cetuximab (400-mg/m² LD; 250-mg/m² MD weekly) + cisplatin (100 mg/m² q3w) or carboplatin (area under the curve [AUC] of 5) for 6 cycles or until toxicity, disease progression, or withdrawal. Primary endpoints were dose-limiting toxicities (DLTs; grade ≥3 [21-day observation period]) and treatment-emergent adverse events (TEAEs). Pharmacokinetics, human antihuman antibodies (HAHA), tumor response, progression free survival (PFS), and overall survival (OS) were assessed. Results: Fifteen patients completed a median (range) of 8.7 (2.0-20.7) patritumab cycles. No DLTs were reported. Serious AEs were reported in 9 patients (patritumab-related n=4). TEAEs (N=15 patients) led to patritumab interruption in 7 patients. Patritumab-related dose reductions were reported in 1 patient. Patritumab (18 mg/kg) pharmacokinetics (N=15) showed mean (standard deviation) AUC_0-21d 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; N=15) was 47%. Median (95% confidence interval) PFS and OS (N=15) were 7.9 (3.7-9.7) and 13.5 (6.6-17.5) months, respectively. Conclusion: Patritumab (18-mg/kg LD, 9-mg/kg MD) plus cetuximab/platinum was tolerable, active in SCCHN, and was selected as the phase II dose-regimen.

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