Makoto Nishio1, Atsushi Horiike2, Haruyasu Murakami3, Nobuyuki Yamamoto4, Hiroyasu Kaneda5, Kazuhiko Nakagawa6, Hidehito Horinouchi7, Masaki Nagashima8, Masaru Sekiguchi9, Tomohide Tamura10. 1. Department of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan. Electronic address: mnishio@jfcr.or.jp. 2. Department of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan. Electronic address: atsushi.horiike@jfcr.or.jp. 3. Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan. Electronic address: ha.murakami@scchr.jp. 4. Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan. Electronic address: nbyamamo@wakayama-med.ac.jp. 5. Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osakasayama, Osaka 589-8511, Japan. Electronic address: kaneda_h@dotd.med.kindai.ac.jp. 6. Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osakasayama, Osaka 589-8511, Japan. Electronic address: nakagawa@med.kindai.ac.jp. 7. Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. Electronic address: hhorinou@ncc.go.jp. 8. Clinical Development Department II, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: nagashima.masaki.ns@daiichisankyo.co.jp. 9. Clinical Development Department II, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: sekiguchi.masaru.f3@daiichisankyo.co.jp. 10. Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. Electronic address: tamuratomohide@gmail.com.
Abstract
OBJECTIVES: Human epidermal growth factor receptor 3 (HER3) is a key dimerization partner for HER family members and is associated with resistance to other HER family receptor-targeted therapeutics. This study evaluated the safety, tolerability, pharmacokinetics and efficacy of patritumab (U3-1287), a fully human anti-HER3 monoclonal antibody, in combination with erlotinib, an epidermal growth factor receptor-tyrosine kinase inhibitor in patients with previously treated advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: This study enrolled patients with stage IIIB/IV NSCLC with Eastern Cooperative Oncology Group performance status 0-1, life expectancy >3 months and who had progressed after at least one prior course of chemotherapy (excluding erlotinib). This open-label study included two parts: dose escalation (Part 1) and dose expansion (Part 2). In Part 1, patients received intravenous patritumab 9 or 18 mg/kg every 3 weeks in addition to per-oral erlotinib 150 mg/day daily. In Part 2, patients received the recommended dose of patritumab as determined in Part 1. Adverse event rates, pharmacokinetics and tumor responses were determined. RESULTS: Twenty-four Japanese patients received patritumab at 9 mg/kg (n=3) or 18 mg/kg (n=21), and erlotinib. No dose-limiting toxicities were reported, indicating the maximum-tolerated dose was not reached. The most frequent adverse events were gastrointestinal or skin toxicities, which were generally mild and manageable. Patritumab pharmacokinetics were similar to those reported in previous studies. The median progression-free survival (95% confidence interval) was 44.0 (22.0-133.0) days for the EGFR wild-type group (n=9) and 107.0 (74.0-224.0) days for the EGFR-activating mutation group (n=13). Evaluation of biomarkers by immunohistochemical analysis did not indicate a relationship between efficacy and HER3 expression in tumor tissues. CONCLUSION: Patritumab in combination with erlotinib was well tolerated and the efficacy of the combination was encouraging, especially in patients where prior gefitinib treatment failed.
OBJECTIVES:Human epidermal growth factor receptor 3 (HER3) is a key dimerization partner for HER family members and is associated with resistance to other HER family receptor-targeted therapeutics. This study evaluated the safety, tolerability, pharmacokinetics and efficacy of patritumab (U3-1287), a fully human anti-HER3 monoclonal antibody, in combination with erlotinib, an epidermal growth factor receptor-tyrosine kinase inhibitor in patients with previously treated advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: This study enrolled patients with stage IIIB/IV NSCLC with Eastern Cooperative Oncology Group performance status 0-1, life expectancy >3 months and who had progressed after at least one prior course of chemotherapy (excluding erlotinib). This open-label study included two parts: dose escalation (Part 1) and dose expansion (Part 2). In Part 1, patients received intravenous patritumab 9 or 18 mg/kg every 3 weeks in addition to per-oral erlotinib 150 mg/day daily. In Part 2, patients received the recommended dose of patritumab as determined in Part 1. Adverse event rates, pharmacokinetics and tumor responses were determined. RESULTS: Twenty-four Japanese patients received patritumab at 9 mg/kg (n=3) or 18 mg/kg (n=21), and erlotinib. No dose-limiting toxicities were reported, indicating the maximum-tolerated dose was not reached. The most frequent adverse events were gastrointestinal or skin toxicities, which were generally mild and manageable. Patritumab pharmacokinetics were similar to those reported in previous studies. The median progression-free survival (95% confidence interval) was 44.0 (22.0-133.0) days for the EGFR wild-type group (n=9) and 107.0 (74.0-224.0) days for the EGFR-activating mutation group (n=13). Evaluation of biomarkers by immunohistochemical analysis did not indicate a relationship between efficacy and HER3 expression in tumor tissues. CONCLUSION:Patritumab in combination with erlotinib was well tolerated and the efficacy of the combination was encouraging, especially in patients where prior gefitinib treatment failed.
Authors: Osamu Tetsu; Matthew J Hangauer; Janyaporn Phuchareon; David W Eisele; Frank McCormick Journal: Chemotherapy Date: 2016-02-25 Impact factor: 2.544
Authors: John S Schardt; Madeleine Noonan-Shueh; Jinan M Oubaid; Alex Eli Pottash; Sonya C Williams; Arif Hussain; Rena G Lapidus; Stanley Lipkowitz; Steven M Jay Journal: AAPS J Date: 2019-04-04 Impact factor: 4.009
Authors: Jose Mauricio Mota; Katharine Ann Collier; Ricardo Lima Barros Costa; Timothy Taxter; Aparna Kalyan; Caio A Leite; Young Kwang Chae; Francis J Giles; Benedito A Carneiro Journal: Oncotarget Date: 2017-06-13
Authors: Jacob Elebro; Margareta Heby; Carl Fredrik Warfvinge; Björn Nodin; Jakob Eberhard; Karin Jirström Journal: PLoS One Date: 2016-04-12 Impact factor: 3.240