Abstract
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).
Highlights
Epidermal growth factor receptor (EGFR), a transmembrane receptor belongs to the family of human epidermal growth factor receptor (HER), is involved in multiple signaling pathways including cell proliferation, motility, angiogenesis, Anti-EGFR monoclonal antibodies (mAbs) are recommended by most international guidelines for the treatment of metastatic colorectal cancer [9, 10] as well as head and neck cancer [11, 12]
Results from multiple Phase III studies showed that the addition of cetuximab or panitumumab to best supportive care or chemotherapy led to improvements in response rates and survival in patients with metastatic colorectal cancer and head and neck cancer [13,14,15,16,17,18]
Cetuximab monotherapy is associated with adverse events (AEs) including skin reactions, Invest New Drugs (2021) 39:1315–1323 hypomagnesaemia, mucositis and infusion-related reactions [19]
Summary
Epidermal growth factor receptor (EGFR), a transmembrane receptor belongs to the family of human epidermal growth factor receptor (HER), is involved in multiple signaling pathways including cell proliferation, motility, angiogenesis, Anti-EGFR mAbs are recommended by most international guidelines for the treatment of metastatic colorectal cancer [9, 10] as well as head and neck cancer [11, 12]. Of the approved anti-EGFR mAbs, cetuximab and panitumumab are extensively studied and most widely used. Results from multiple Phase III studies showed that the addition of cetuximab or panitumumab to best supportive care or chemotherapy led to improvements in response rates and survival in patients with metastatic colorectal cancer and head and neck cancer [13,14,15,16,17,18]. Skin reactions occurred in the majority of patients (80%) who receive cetuximab [20]. A meta-analysis of the safety of cetuximab in metastatic colorectal cancer found that Grade 3–4 AEs occurred in around 60% of patients, and 90% of patients experienced infusion-related reactions following the first infusion [20]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
