Phase 2 romosozumab sclerostin-directed monoclonal antibody as bone-anabolic therapy in bone-metastatic ER/PR+ breast cancer

Memorial Sloan Kettering Cancer Center is running REMOLD-Breast (Phase 2) to test whether romosozumab (Evenity; Amgen/UCB)—a sclerostin-neutralizing monoclonal antibody that increases bone formation and also reduces bone resorption—can safely improve bone turnover in people with metastatic breast cancer with bone metastases who also have osteoporosis and high fracture risk. The design is a single-arm interventional study using on-label romosozumab 210 mg subcutaneously once monthly, with endpoints centered on bone formation markers (e.g., P1NP) and resorption markers alongside safety monitoring. The eligible population is ER/PR+ metastatic breast cancer with confirmed bone metastases and documented osteoporosis, continuing their anticancer therapy while adding the bone-directed agent. The scientific/commercial angle is that this brings an anabolic osteoporosis drug into the metastatic bone disease setting, where most bone-modifying therapy is antiresorptive rather than bone-building. Today’s care for ER/PR+ MBC is endocrine therapy plus targeted agents (often CDK4/6 inhibitors) with zoledronic acid (Novartis) or denosumab (Amgen) to reduce skeletal-related events, while osteoporosis management typically relies on antiresorptives; this trial asks if an anabolic approach can improve bone strength without unacceptable cardiovascular or oncologic tradeoffs.