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) AUC0-21d 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.