SOLACE: A phase 1 pharmacokinetic, dosimetry, safety, and dose optimization study for a single dose of ¹⁵³ Sm-DOTMP to treat metastatic bone pain.

TPS271 Background: With patients with bone metastases commonly report pain and significant degradations in quality of life, current treatment options have limitations. Patients may not experience effective relief, and treatments often cause myelotoxicity and high costs. Bone pain is one of the most common forms of pain reported by patients with metastatic disease and significantly degrades quality of life. DOTMP is a bone-seeking chelating agent, and when radiolabeled with samarium-153 ( 153 Sm-DOTMP) is a therapeutic radiopharmaceutical that emits both beta particles and gamma photons to bone metastases. Prior Phase I experience (QSAM-101, n=5) demonstrated no DLTs, manageable hematologic toxicity, and early signals of pain relief. The Phase 1 Samarium Optimized for Long-lasting Analgesia in Cancerous End-stage bone pain (SOLACE) study aims to evaluate pharmacokinetics (PK), dosimetry, safety, and efficacy of a single dose of 153 Sm-DOTMP for the treatment of pain associated with metastatic bone cancer. Methods: This open-label, Phase 1 study includes dose escalation (Part A, n=9-15, up to 3 cohorts) and dose selection (Part B, n=18) in patients with painful metastatic bone lesions. In Part A, 3 patients per cohort will be enrolled in parallel into Cohort 1 and 2 and will receive 0.5 mCi/kg or 1.0 mCi/kg of intravenous 153 Sm-DOTMP, respectively. (Cohort 1: 0.5 mCi/kg; Cohort 2: 1.0 mCi/kg; Cohort 3: 1.5 mCi/kg). If no dose-limiting toxicities (DLTs) are seen in Cohort 2, 3 patients will be enrolled in Cohort 3 (1.5 mCi/kg intravenous 153 Sm-DOTMP). Cohorts 2 and 3 will enroll 3 additional participants if only 1/3 patients had DLT at that cohort; if ≥2 DLTs are seen, no further patients will be recruited at that dose level, and it will be declared a non-tolerated dose. The DLT observation period will be 6 weeks after administration, during which safety and tolerability will be closely monitored. Eligible patients will be aged ≥18 years with histologically confirmed malignancy with multiple metastatic bone lesions including ≥1 confirmed painful (pain score of ≥4 on Numeric Rating Scale 11 [NRS-11]) osteoblastic bone tumor that exhibits avid update as shown by 99m Tc-diphosphonate bone scans ≤60 days of 153 Sm-DOTMP administration. Patients will have had disease progression while on anti-cancer treatment or ineligible for such treatments with painful bone lesions not amenable to palliative EBRT. Patients must have been receiving a stable regimen of bisphosphonates and/or hormonal or endocrine therapy for ≥3 months prior to 153 Sm-DOTMP administration. This study is currently enrolling. Clinical trial information: NCT07197645 .