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Phase 1 study of anti-epidermal growth factor receptor monoclonal antibody in patients with solid tumors.

ABSTRACT: In the present study, we conducted a Phase 1 study of a recombinant anti-EGFR monoclonal antibody (CMAB009) that has the same amino acid sequence as cetuximab. The purpose of this study was to evaluate the safety, pharmacokinetics, and potential benefit of CMAB009 in Chinese patients with advanced chemotherapy-resistant epithelial malignancies. In this study, 18 patients were treated with two successive treatment schedules comprising a single-dose escalation phase followed by a weekly, multiple-dose extension phase. No dose-limiting toxicity was reported during the evaluation period. CMAB009-associated toxicity was minimal, and the most commonly reported adverse events were fever, asthenia, transaminase elevation, nausea, and skin toxicities. CMAB009 exhibited a non-linear PK profile over the dose range of 100 to 400 mg/m2. In the single-dose phase, CMAB009 reached peak serum concentrations at the end of the infusion and then declined slowly with a Tl/2 of 77.15 ±13.96 h, 79.79 ±6.91 h, and 86.25 ±9.93 h after infusion of 100, 250, and 400 mg/m ( 2) based on a two compartmental model analysis. Mean Cmax increased roughly dose-proportional while AUC0-? showed a greater than dose-proportionate increase from 100 to 400 mg/m ( 2) . After multiple infusions, serum concentrations dropped slowly and the Tl/2 was 102.25 ± 33.54 h and 118.91 ± 29.12 h based on a two compartmental model analysis. No neutralizing anti-antibody antibodies were detectable. Two patients achieved partial remissions. The study results suggest that CMAB009 shows acceptable tolerance and primary efficacy and should be studied as a treatment in patients with advanced chemotherapy-resistant epithelial malignancies.

SUBMITTER: Wang C

PROVIDER: S-EPMC3038013 | biostudies-literature | 2011 Jan-Feb

REPOSITORIES: biostudies-literature

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Phase 1 study of anti-epidermal growth factor receptor monoclonal antibody in patients with solid tumors.

Wang Chong C He Xiaohui X Zhou Bo B Li Jing J Li Bohua B Qian Weizhu W Hou Sheng S Wang Hao H Shi Yuankai Y Guo Yajun Y

mAbs 20110101 1

In the present study, we conducted a Phase 1 study of a recombinant anti-EGFR monoclonal antibody (CMAB009) that has the same amino acid sequence as cetuximab. The purpose of this study was to evaluate the safety, pharmacokinetics, and potential benefit of CMAB009 in Chinese patients with advanced chemotherapy-resistant epithelial malignancies. In this study, 18 patients were treated with two successive treatment schedules comprising a single-dose escalation phase followed by a weekly, multiple- ...[more]

PMID: 21051930

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Project description:BackgroundEpidermal 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.ObjectivesTo assess the safety, tolerability, pharmacokinetics (PK), and immunogenicity of Ametumumab.DesignA first-in-human phase Ia dose escalation study of Ametumumab in patients with advanced solid malignancies.MethodsAn 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.ResultsIn 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%.ConclusionThe 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.RegistrationThe trial was registered with CTR20170343 on 10 April 2017, The China Center for Drug Evaluation.

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Phase 1 study of anti-epidermal growth factor receptor monoclonal antibody in patients with solid tumors.

Publications

Phase 1 study of anti-epidermal growth factor receptor monoclonal antibody in patients with solid tumors.

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