Phase 1 study of new formulation of patritumab (U3-1287) Process 2, a fully human anti-HER3 monoclonal antibody in combination with erlotinib in Japanese patients with advanced non-small cell lung cancer

• Published in: Cancer chemotherapy and pharmacology Vol. 79; no. 3; pp. 489 - 495
• Main Authors: Shimizu, Toshio, Yonesaka, Kimio, Hayashi, Hidetoshi, Iwasa, Tsutomu, Haratani, Koji, Yamada, Hironori, Ohwada, Shoichi, Kamiyama, Emi, Nakagawa, Kazuhiko
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-03-2017; Springer Nature B.V
• Subjects: Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Neutralizing - administration & dosage; Antineoplastic Agents - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - blood; Cancer Research; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Disease-Free Survival; Drug Compounding; Erlotinib Hydrochloride - administration & dosage; Female; Humans; Injections, Intravenous; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation; Oncology; Original; Original Article; Pharmacology/Toxicology; Protein Kinase Inhibitors - administration & dosage; Receptor, Epidermal Growth Factor - genetics; Receptor, ErbB-3 - immunology; Phase 1 study; Pharmacokinetics; Patritumab; Anti-HER3 monoclonal antibody
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-016-3231-3

Background
This phase 1 study evaluated the safety, tolerability, pharmacokinetics and efficacy of patritumab (U3-1287) Process 2, a new formulation of fully human anti-HER3 monoclonal antibody in combination with erlotinib, an epidermal growth factor receptortyrosine kinase inhibitor (EGFR-TKI) in prior chemotherapy treated Japanese patients with advanced non-small cell lung cancer (NSCLC).
Methods
Patients received intravenous patritumab Process 2 formulation at 9 mg/kg every 3 weeks after initiation of 18 mg/kg loading dose combined with continuous daily dose of erlotinib (150 mg QD) until any of the withdrawal criteria are met. Adverse events (AEs) were assessed using CTCAE v4.0 and tumor response was assessed using RECIST v1.1. Full pharmacokinetic sampling and serum biomarker analyses were mainly performed during cycle 1 and 2.
Results
Total of six EGFR-mutant NSCLC patients including one EGFR-TKI naïve patient received patritumab Process 2 formulation combined with erlotinib. No dose-limiting toxicities were observed. The most frequent AEs were gastrointestinal or skin toxicities, which were generally mild and manageable. One patient discontinued from study due to reversible grade 3 interstitial lung disease. The mean area under the curve (AUC) value was 2640 μg/day/mL; the Cmax value was 434 μg/mL, respectively. The median progression-free survival (95% confidence interval) was 220.0 (100.0–363.0) days. HER3 ligand heregulin was detected in serum from only a patient that maintained most durable stable disease.
Conclusions
Patritumab Process 2 formulation in combination with erlotinib was well tolerated compatible with favorable PK profile in Japanese patients with advanced NSCLC.