A Study of HLX06, a Humanized Monoclonal Antibody Targeting Human Vascular Endothelial Growth Factor Receptor-2 in Patients With Advanced Solid Tumors
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|ClinicalTrials.gov Identifier: NCT03494231|
Recruitment Status : Recruiting
First Posted : April 11, 2018
Last Update Posted : April 11, 2018
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumor, Adult||Drug: HLX06||Phase 1|
Angiogenesis plays an important role in cancer development. The VEGF family and their receptors (VEGFR) are well characterized for their role in neoplastic angiogenesis. VEGFR2 belongs to type V receptor tyrosine kinase encoded by KDR gene, and is expressed in vascular endothelial cells. It is a primary responder to vascular endothelial growth factor signal that regulates endothelial migration and proliferation. The expression of VEGFR2 can be found in multiple tumor types, including angiosarcoma, Kaposi sarcoma. In epithelial carcinoma, VEGFR2 expression can be found in mesothelioma, non-small cell lung cancer, and embryonal carcinoma. Targeting angiogenesis using either small molecule inhibitors or biological agents have been widely used in current cancer management. Current approved anti-angiogenesis biological agents include bevacizumab, ramucirumab, aflibercept. Among them, ramucirumab (IMC-1121B) targets vascular endothelial growth factor receptor 2 (VEGFR2). Ramucirumab has been approved for use in combination with paclitaxel for second-line treatment of patients with advanced gastric or gastroesophageal junction adenocarcinoma.
Although ramucirumab has been approved for gastric cancer, its improvement in overall survival is still not satisfactory. It prolongs the overall survival by 6 weeks when combined with paclitaxel. So far, there is not biomarker available to predict the efficacy of ramucirumab. Therefore, a new monoclonal antibody also targeting VEGFR2 might provide better efficacy for cancer patients.
HLX06 is a new, fully human monoclonal antibody targeting VEGFR2. It has better binding affinity to VEGFR2, and also binds to different region in VEGFR2. In vitro studies have demonstrated the growth inhibition of human endothelial cells, and HLX06 has shown growth inhibition of tumors in xenogeneic studies.
Nonclinical studies up to weekly 150 mg/kg in cynomolgus monkeys for 13 weeks have shown good tolerability without evident toxicities (please refer to Investigator's brochure). HLX06 shows cross-reactivity to both monkey and human VEGFR2, but does not bind rodent VEGFR2. The investigators expect that HLX06 will provide a better alternative than ramucirumab for patients with advanced cancers.
However, HLX06 has not yet been tested in humans. Therefore, the investigators propose this first-in-human phase 1 study. In this study, the investigators intend to monitor the safety and tolerability of HLX06 in humans, and hope to identify the maximum tolerated dose, and determine the recommended phase 2 dose for future study. At the same time, the investigators would like to collect information of the pharmacokinetics and pharmacodynamics of this drug and its potential immunogenicity.
To minimize the risk of patients who volunteer to receive this experimental drug, the investigators have selected 250 mg flat dose as the starting dose. The reason for using flat dosing instead of body weight-adjusted dosing is based on previous population pharmacokinetic studies for multiple monoclonal antibody drugs. The 500 mg flat dose was conservatively selected to provide sufficient safety factor in the FIH study, based on 1/6 of the human equivalent dose (1/3) of the highest non-severely toxic dose (HNSTD) in 3 month repeat-dose studies in cynomolgus monkeys.
To investigate the dose required to reach maximal effect, the investigators propose a dose escalation sequence. The purpose of the dose escalation is to obtain the pharmacokinetics and pharmacodynamics of HLX06 at different dose levels, and investigate its relationship with adverse reactions. Also, the investigators intend to identify the MTD. The information from the dose escalation is crucial to determine the optimal dose in future studies and potential indications for HLX06.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-label, Dose Escalation Phase 1 Study to Investigate HLX06, a Humanized Monoclonal Antibody Targeting Human Vascular Endothelial Growth Factor Receptor-2, in Patients With Advanced Solid Tumors Refractory to Standard Therapy|
|Actual Study Start Date :||March 22, 2018|
|Estimated Primary Completion Date :||August 2019|
|Estimated Study Completion Date :||February 2020|
Experimental: HLX06, in patients with solid cancers
Each cycle of treatment consists of 4 weeks. Patients who enroll into this study will receive an infusion of assigned dose of HLX06 once per week. No intra-patient dose escalation is allowed. The proposed dose escalation sequence is 500, 750, 900, 1200, 1500 mg, starting from 500 mg/kg.
recombinant fully human anti-VEGFR2 monoclonal antibody against cancers
Other Name: anti-VEGFR2 monoclonal antibody
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 1.5 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03494231
|Contact: Eugene Liu, MD, PhDfirstname.lastname@example.org|
|Contact: Shufan Lin, MSemail@example.com|
|Taipei Medical University-Shuang Ho Hospital||Recruiting|
|New Taipei City, Taiwan, 23561|
|Contact: Principal Investigator|
|Principal Investigator:||Tus-Yi Chao, MD||Taipei Medical University Shuang Ho Hospital|