A phase Ia dose-escalation trial of Ametumumab (a fully human monoclonal antibody against epidermal growth factor receptor) in patients with advanced solid malignancies

Author:

Li Da1ORCID,Pan Hong1,Wang Wei1,Xue Yanan1ORCID,Fang Yong1,Lou Haizhou1,Pan Qin1,Jin Wei1,Zheng Yu1,Han Weidong1,Zhu Kongli2,Zhao Xianfeng2,Xu Rong2,Han Jin3,Pan Hongming4ORCID

Affiliation:

1. Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine, Hangzhou, China

2. Shanghai Celfuture Biotech Co., Ltd., Shanghai, China

3. Shanghai Celfuture Biotech Co., Ltd., No. 280 Juli Rd. Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, China

4. Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine, No. 3 East Qingchun Road, Hangzhou, Zhejiang 310016, China

Abstract

Background: Epidermal growth factor receptor (EGFR) is a well-known target for cancer treatment. However, the authorized anti-EGFR monoclonal antibodies generally cause several toxic effects, especially severe cutaneous toxicities as well as infusion reactions, and the clinical indications are limited. Here we developed Ametumumab, a fully human recombinant anti-EGFR monoclonal antibody. Objectives: To assess the safety, tolerability, pharmacokinetics (PK), and immunogenicity of Ametumumab. Design: A first-in-human phase Ia dose escalation study of Ametumumab in patients with advanced solid malignancies. Methods: An open-label, first-in-human dose escalation study was done in 22 patients with advanced malignancies who received six ascending dosages ranging from 75 to 750 mg/m2. Following a single dosage and a 28-day dose-limiting toxicity (DLT) monitoring period, patients were given repeated doses weekly. Blood samples were taken to determine the PK parameters of Ametumumab and anti-drug antibody concentrations. Every 8 weeks, radiographic tumor evaluations were conducted. Results: In this trial, no DLT was observed, and the maximum tolerated dose was not reached at doses up to 750 mg/m2. There were no severe adverse events but mild and moderate adverse effects, such as headache, proteinuria, and rash. Single-dose PK results demonstrated a straightforward linear relationship with dosage escalation. The medication concentrations accumulated and attained steady-state after four rounds of injections. It was calculated that 10 patients with disease control would be observed in the 22 evaluable patients. The disease control rate was 45.5%. Conclusion: The Ametumumab was well tolerated and safe in patients with advanced solid malignancies, exhibiting minimal immunogenicity, a long half-life, high levels of drug exposure in the blood, and preliminary effectiveness. Registration: The trial was registered with CTR20170343 on 10 April 2017, The China Center for Drug Evaluation.

Funder

Shanghai Science and Technology Development Foundation of Shanghai Science and Technology Commission

National Major Science and Technology Project of China for Significant New Drugs Development during the Thirteen Five-year Plan Period

Publisher

SAGE Publications

Subject

Oncology

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