Phase I first-in-human study of HLX07, a novel and improved recombinant anti-EGFR humanized monoclonal antibody, in patients with advanced solid cancers
Autor: | Xiaodi Zhang, Yunting Zhu, Ching-Liang Ho, Hsuan-Yu Lin, Ming-Mo Hou |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Monoclonal antibody Adult Male medicine.medical_specialty Efficacy Maximum Tolerated Dose Nausea Taiwan Antineoplastic Agents Antibodies Monoclonal Humanized 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Internal medicine Phase I Studies Neoplasms Solid tumors medicine Clinical endpoint Humans Pharmacology (medical) Prospective Studies Adverse effect Aged Pharmacology Aged 80 and over Toxicity Dose-Response Relationship Drug business.industry Middle Aged Clinical trial ErbB Receptors 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cohort Vomiting Female medicine.symptom business |
Zdroj: | Investigational New Drugs |
ISSN: | 1573-0646 0167-6997 0264-8490 |
Popis: | SummaryPurpose This study aimed to evaluate the safety and pharmacokinetic (PK) profiles of HLX07, a novel, recombinant, humanized anti-epidermal growth factor receptor (EGFR) antibody, in patients with advanced solid cancers who had failed standard therapy or for whom no standard therapy was available. Methods In this prospective, open-label, Phase I dose escalation study, patients aged ≥18 years (≥20 years for patients in Taiwan) with histologically-confirmed metastatic or recurrent epithelial carcinoma that had no K-RAS or B-RAF mutations were enrolled in a ‘3 + 3’ escalation design. HLX07 was administered weekly by 2-h intravenous infusion at doses ranging from 50 to 800 mg. The primary endpoint was summary listing of participants reporting treatment-emergent adverse events (TEAEs). Secondary endpoints included PK analysis, serum anti-HLX07 antibody assessments and efficacy. Results In total, 19 patients were enrolled between 1 October 2016 and 16 July 2019 to receive HLX07 at doses of 50 (n = 3), 100 (n = 3), 200 (n = 3), 400 (n = 3), 600 (n = 3) and 800 (n = 4) mg per week. All patients experienced at least one TEAE, most commonly fatigue (68.4%), nausea (47.4%), paronychia (31.6%) and vomiting (31.6%). Serious TEAEs were reported in 11 patients but only one serious TEAE (dyspnea in 600 mg cohort) was regarded as possibly related to study treatment. No dose limiting toxicity (DLT) was reported. Systemic exposure to HLX07 increased proportionally with dose. Anti-HLX07 antibodies were not detected in any patients. Conclusion HLX07 was well tolerated (at dose levels up to 800 mg/week) and promising in patients with advanced solid cancers.Clinical Trial Registration: The study was registered at ClinicalTrials.gov: NCT02648490 (Jan 7, 2016). |
Databáze: | OpenAIRE |
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