A Phase I Study of Nimotuzumab Combined with Irinotecan in Chinese Patients with Advanced Solid Tumors

Abstract Nimotuzumab is an anti‐epidermal growth factor receptor antibody. This Phase I study evaluated the pharmacokinetics and safety of nimotuzumab plus irinotecan in Chinese patients with advanced solid tumors. At single ascending dosage (SAD) stage, four cohorts (100, 200, 400, and 600 mg) of patients received nimotuzumab intravenously on Day 1, alongside irinotecan 180 mg/m 2 on Day 8. Three weeks later, all patients in the four cohorts transferred to multiple ascending dosage (MAD) stage: nimotuzumab was administrated weekly for 6 weeks, alongside irinotecan (Days 1, 15, 29, 43, and 57, 180 mg/m 2 ). Primary objective was pharmacokinetics, safety and tolerability was also examined. From December 2012 to October 2014, in SAD and MAD stages, there were 28 and 39 patients with Stage IV solid tumors. The area under the concentration curve (AUC 0–∞ ) for a single dose of nimotuzumab was 10.2 ± 2.7 (100 mg), 37.6 ± 10.0 (200 mg), 114.8 ± 35.5 (400 mg), 197.6 ± 32.0 (600 mg) (×100 h µg/mL), and for multiple dose, it was 26.7 ± 3.4 (100 mg), 87.1 ± 12.0 (200 mg), 193.4 ± 46.9 (400 mg) and 446.3 ± 100.7 (600 mg) (×100 h µg/mL). There was low incidence of rash and no dose‐limiting toxicities occurred. This study indicated that nimotuzumab at doses ranging from 100 to 600 mg exhibited a manageable and tolerable safety profile.