A phase 1b study of SHR-2017, a RANKL/NGF targeted antibody, in patients (pts) with breast cancer bone metastasis.

Abstract

12059 Background: Bone metastasis is a common site of metastasis in malignant tumors. For patients (pts) with bone metastasis, pain is the predominant symptom, significantly impairing the quality of life. SHR-2017, a first-in-class fully human monoclonal antibody targeting RANKL/NGF, is designed to prevent skeletal-related events and alleviate pain in pts with bone metastasis. Here, we present the preliminary pharmacokinetics, pharmacodynamics, efficacy and safety results from a multicenter, open-label, single-arm phase 1b study in pts with bone metastasis from breast cancer. Methods: Breast cancer pts with at least one bone metastasis and an average Numeric Rating Scale (NRS) score of ≥ 4 at the index bone metastasis cancer pain site at baseline were eligible. Pts could be undergoing stable anti-tumor treatment or have no plan to change their anti-tumor treatment within 2 weeks after drug administration in this study. Pts received subcutaneous injection of SHR-2017 at 180 mg every 4 weeks for 6 cycles. To assess pain, pts maintained a diary (daily through week 8 and then weekly to week 48) to record the average and worst pain over the previous 24 h (on a numeric rating scale from 0 = no pain to 10 = worst possible pain) at the index bone metastasis cancer pain site. Results: As of Dec 31, 2024, 22 pts were enrolled and treated (prior bone targeted agents [BTA] use, 36%; mean NRS of average pain, 4.17 [SD: 0.76]). Following a single dose, the median time to peak concentration of SHR-2017 was 7 days, with a mean half-life (t 1/2 ) of 11.4 days and a mean clearance (CL/F) of 0.88 L/day. Among 12 pts without prior BTA use, a reduction in urine N-telopeptide of type I collagen adjusted for urine creatinine (uNTX/Cr), a biomarker for bone resorption, was evident by cycle 1 and sustained over time; the median reduction from baseline was -83.0% (range -96.9% to -60.6%) at week 5 (C2D1). By week 13 (C4D1), among 8 pts without prior BTA use, the median reduction in uNTX/Cr was -78.7% (range -93.1% to -64.6%). Daily NRS score showed a continuous decrease during cycle 1 in all pts, the mean reductions from baseline in average and worst pain were -1.95 (SD: 1.21) and -1.90 (SD: 1.46) at week 2, respectively. By week 4, the reductions were -2.46 (SD: 1.03) and -2.45 (SD: 1.45), respectively. Treatment-related AEs (TRAEs) occurred in 7 (32%) pts (grade 1, n = 6; grade 2, n = 1), with the most common being increased parathyroid hormone (PTH), the one grade 2 TRAE being rash. There were no TRAEs leading to dose discontinuation. Conclusions: Preliminary data indicated promising anti-bone resorption and analgesic effects, with a favorable safety profile for SHR-2017 in pts with bone metastasis from breast cancer. The trial is ongoing to further evaluate SHR-2017 following multiple dosing. Clinical trial information: NCT06380881 .