Abstract P1-18-03: Phase I trial to assess the safety, pharmacokinetics and pharmacodynamics of receptor activator of nuclear factor-κB ligand inhibitor (TK006) in patients with bone metastases from breast cancer
Abstract
Background Within the bone microenvironment, tumor cells secrete factors that stimulate osteoblasts to express and secrete receptor activator of nuclear factor-κB ligand (RANKL), which binds to its receptor RANK on the surface of osteoclasts, thus enhancing the osteoclast-mediated bone resorption and promoting skeletal complications.TK006 is a fully human monoclonal antibody that binds and inhibits RANKL, thus inhibiting osteoclast-mediated bone destruction. Objective To investigate the safety, pharmacokinetics and pharmacodynamics of TK006 in patients with bone metastases from breast cancer. Patients and methods In this dose-escalating study, patients were sequentially enrolled into 60 mg, 120 mg, 180 mg single-dosing and 120 multiple-dosing cohorts. Before making dose escalation decision, the safety of TK006 during the 14-day period after dosing in the prior cohort must be confirmed. In the three single-dosing cohorts, patients were followed up for 16 weeks after dosing. In the 120 mg multiple-dosing cohort, patents were treated with 120 mg TK006 every 4 weeks for 3 times totally, and followed up for 20 weeks after the first dosing. The primary outcome was safety profile, and the secondary outcomes were pharmacokinetics, pharmacodynamics and immunogenicity. Pharmacodynamics was measured by level of serum bone alkaline phosphatase (BALP) and urine creatinine corrected cross-linked N-telopeptides of type I collagen (uNTX/Cr). Patients aged 18 to 65 years with breast cancer…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 40 participants or records.
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