A phase I and pharmacokinetic study of afilbercept with FOLFIRI: comparison of Chinese and Caucasian populations.

Background This study assessed the preliminary safety, pharmacokinetics (PK) and anti-tumor effects of aflibercept in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) in Chinese patients with previously-treated advanced solid malignancies. Patients and Methods This open-label single-arm Phase I study conducted at two centers in China included adult (≥18 years) patients with metastatic or unresectable solid malignancies who had received ≥1 prior treatment. Patients received aflibercept 4 mg/kg IV on Day 1 followed by FOLFIRI over Days 1 and 2 every 2 weeks, and were assessed for safety, tumor response, PK parameters and immunogenicity. Post-hoc analyses included calculation of progression-free survival (PFS) for patients with colorectal cancer (CRC). Results A total of 20 patients were enrolled. The most common Grade 3/4 adverse events included neutropenia (35%), hypertension (30%), stomatitis (20%) and proteinuria (20%), and no anti-aflibercept antibodies were detected. Six patients achieved a partial response, and in 15 patients with CRC median PFS was 5.95 months (95% CI: 5.29-8.77). Free aflibercept remained in excess of VEGF-bound aflibercept for the majority of the study treatment duration. The mean free aflibercept values for Cmax (64.8 μg/mL) AUC (291 μg.day/mL), CL (0.92 L/day) and Vss (5.9 L) were similar to those measured in Caucasian patients. The addition of aflibercept did not influence the PK of the chemotherapy agents. Conclusion For Chinese patients with pre-treated advanced solid malignancies, 4 mg/kg of aflibercept in combination with FOLFIRI was well-tolerated, demonstrated preliminary anti-tumor activity and had a PK profile consistent with that in Caucasian patients.