A multicenter, randomized, double-blind trial comparing LY01011, a biosimilar, with denosumab (Xgeva®) in patients with bone metastasis from solid tumors.

Introduction: Denosumab (Xgeva®) is a standard treatment for the prevention of skeletal-related events (SREs) in patients with bone metastases (BM). This trial was designed to assess the equivalence of LY01011 to denosumab in terms of efficacy and safety. Materials and methods: Eligible patients with BM from solid tumors were randomized at a 1:1 ratio to receive 120 mg of LY01011 or 120 mg of denosumab subcutaneously every four weeks during a 12-week double-blind treatment period, and then all enrolled patients continued to receive LY01011 until week 53. The primary endpoint was the natural logarithm of change of the urinary N-terminal crosslinked telopeptide of type I collagen level normalized to the urine creatinine level (uNTX/uCr) at week 13 from baseline. Other endpoints included the uNTX/uCr ratio, serum bone-specific alkaline phosphatase level alteration, status of anti-drug antibodies and neutralizing antibodies, adverse events and SREs. Results: 850 eligible patients were randomized into the LY01011 group (n = 424) or the denosumab group (n = 426). The least-squares means (SEs) of the natural logarithms of the changes in the uNTX/uCr ratios at week 13 from baseline were -1.810 (0.0404) in the LY01011 group and -1.791 (0.0406) in the denosumab group. The LSM difference [90 % CI] between two arms was -0.019 [-0.110, 0.073] within the equivalence margins (-0.135, 0.135) and met the predetermined primary endpoint. The AEs, ADAs and the PK data showed no statistically significant difference. Conclusions: This study demonstrated the equivalent efficacy and safety of LY01011 to denosumab in patients with BM.