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A Phase 1 Study of Necitumumab (Anti-Egfr Monoclonal Antibody) in Japanese Patients with Advanced Solid Tumors
Annals of Oncology 25 (Supplement 5): v44–v74, 2014 doi:10.1093/annonc/mdu435.108
Oral Session (Oral presentations categorized by each organ) O3
9
2
Hiroshi Nokihara1, Noboru Yamamoto1, Yosuke Tamura1, Yuko Tanabe1, Kazunori Honda1, Hajime Asahina1, Sotaro Enatu2, Raffael Kurek3, Yasuhide Yamada4, Tomohide Tamura1 1 Department of Thoracic Oncology, National Cancer Center Hospital 2 Eli Lilly Japan K.K 3 Lilly Deutschland GMBH 4 Department of Gastrointeitinal Oncology, National Cancer Center Hospital
abstracts
Background: Necitumumab (LY3012211; IMC-11F8) is a recombinant human monoclonal antibody (mAb) of the IgG1 class. Based on a Phase 1 study and pharmacokinetic data, the recommended dose (RD) in Western patients is 800 mg weekly or every 2 weeks, or on days (D) 1 and 8 of a 3-week cycle.
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_5/v70/2240212 by guest on 26 October 2019
A PHASE 1 STUDY OF NECITUMUMAB (ANTI-EGFR MONOCLONAL ANTIBODY) IN JAPANESE PATIENTS WITH ADVANCED SOLID TUMORS
Methods: This Phase 1 study investigated necitumumab in Japanese patients with advanced solid tumors. The major objectives were to establish the maximum tolerated dose (MTD), based on the number of patients with dose limiting toxicities (DLTs) during cycle 1 (6 weeks), and to assess safety, pharmacokinetics and preliminary antitumor activity. Patients were enrolled sequentially in a 3 + 3 design provided no DLTs were observed in the previous cohort. Necitumumab was administered intravenously at the following dosing schedules: cohort 1: 600 mg on D1 and 8, every 3 weeks; cohort 2: 800 mg on D1, every 2 weeks; and cohort 3: 800 mg on D1 and 8, every 3 weeks. Results: Fourteen of 15 patients enrolled received all scheduled infusions in cycle 1. The MTD population consisted of 3 patients in cohort 1, 6 patients in cohort 2, and 5 patients in cohort 3. No DLT was observed, and the MTD was not reached. The highest dose levels corresponded with the RD in Western patients; therefore, no additional dose escalations were planned. The most common necitumumab-related adverse events were headache (66.7%), dry skin (66.7%), pruritus (53.3%) and rash (53.3%), nearly all of Grade 1/ 2. Treatment-related hematologic or serum chemistry toxicities ≥ Grade 3 were not observed. For antitumor activity, a disease control rate of 67% was achieved. Pharmacokinetic parameters were analyzed following single and multiple doses; all 3 regimens achieved serum trough concentrations >40 µg/ml, which is associated with antitumor activity in animal models. Conclusion: This Phase 1 study showed that necitumumab can be safely administered to Japanese patients at the same dose regimens recommended for Western patients.
Oral Session (Oral presentations categorized by each organ) O3
9
2
Hiroshi Nokihara1, Noboru Yamamoto1, Yosuke Tamura1, Yuko Tanabe1, Kazunori Honda1, Hajime Asahina1, Sotaro Enatu2, Raffael Kurek3, Yasuhide Yamada4, Tomohide Tamura1 1 Department of Thoracic Oncology, National Cancer Center Hospital 2 Eli Lilly Japan K.K 3 Lilly Deutschland GMBH 4 Department of Gastrointeitinal Oncology, National Cancer Center Hospital
abstracts
Background: Necitumumab (LY3012211; IMC-11F8) is a recombinant human monoclonal antibody (mAb) of the IgG1 class. Based on a Phase 1 study and pharmacokinetic data, the recommended dose (RD) in Western patients is 800 mg weekly or every 2 weeks, or on days (D) 1 and 8 of a 3-week cycle.
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_5/v70/2240212 by guest on 26 October 2019
A PHASE 1 STUDY OF NECITUMUMAB (ANTI-EGFR MONOCLONAL ANTIBODY) IN JAPANESE PATIENTS WITH ADVANCED SOLID TUMORS
Methods: This Phase 1 study investigated necitumumab in Japanese patients with advanced solid tumors. The major objectives were to establish the maximum tolerated dose (MTD), based on the number of patients with dose limiting toxicities (DLTs) during cycle 1 (6 weeks), and to assess safety, pharmacokinetics and preliminary antitumor activity. Patients were enrolled sequentially in a 3 + 3 design provided no DLTs were observed in the previous cohort. Necitumumab was administered intravenously at the following dosing schedules: cohort 1: 600 mg on D1 and 8, every 3 weeks; cohort 2: 800 mg on D1, every 2 weeks; and cohort 3: 800 mg on D1 and 8, every 3 weeks. Results: Fourteen of 15 patients enrolled received all scheduled infusions in cycle 1. The MTD population consisted of 3 patients in cohort 1, 6 patients in cohort 2, and 5 patients in cohort 3. No DLT was observed, and the MTD was not reached. The highest dose levels corresponded with the RD in Western patients; therefore, no additional dose escalations were planned. The most common necitumumab-related adverse events were headache (66.7%), dry skin (66.7%), pruritus (53.3%) and rash (53.3%), nearly all of Grade 1/ 2. Treatment-related hematologic or serum chemistry toxicities ≥ Grade 3 were not observed. For antitumor activity, a disease control rate of 67% was achieved. Pharmacokinetic parameters were analyzed following single and multiple doses; all 3 regimens achieved serum trough concentrations >40 µg/ml, which is associated with antitumor activity in animal models. Conclusion: This Phase 1 study showed that necitumumab can be safely administered to Japanese patients at the same dose regimens recommended for Western patients.