title: 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.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  Patritumab Process 2 formulation in combination with erlotinib was well tolerated compatible with favorable PK profile in Japanese patients with advanced NSCLC.
authors.affiliation: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2, Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan. tosshimi@ncc.go.jp.|Department of Experimental Therapeutics, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. tosshimi@ncc.go.jp.
authors.forename: Toshio
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2, Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
authors.forename: Kimio
authors.initials: K
authors.lastname: Yonesaka
authors.affiliation: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2, Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2, Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Iwasa
authors.affiliation: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2, Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Haratani
authors.affiliation: Oncology Clinical Development Department, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Biostatistics and Data Management Department, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ohwada
authors.affiliation: Translational Medicine and Clinical Pharmacology Department, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Kamiyama
authors.affiliation: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2, Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D000080908:Broadly Neutralizing Antibodies; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D018572:Disease-Free Survival; D004339:Drug Compounding; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D020893:Receptor, ErbB-3 / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000080908:Broadly Neutralizing Antibodies; D047428:Protein Kinase Inhibitors; C585471:patritumab; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; C581292:ERBB3 protein, human; D066246:ErbB Receptors; D020893:Receptor, ErbB-3
keywords: Anti-HER3 monoclonal antibody; Patritumab; Pharmacokinetics; Phase 1 study