Actinium Therapy for Late-stage Aggressive Sarcomas

RTX-2358-101 is an open-label, seamless, Phase 1/2 clinical study to evaluate safety, tolerability, dosimetry, biodistribution, pharmacokinetic (PK), and anti-tumor activity of \[Ac225\]RTX-2358. \[Ac 225\]-RTX-2358 is for patients with relapsed or treatment-resistant soft tissue sarcoma. The study consists of two phases, an ascending administered activity phase (Phase1) and an expansion phase (Phase 2). In the Phase 1 portion of the trial patients will be divided into three groups, each group receiving a higher dose than the last. A modified "3 + 3" dose escalation with Phase 1 queue (IQ) design approach will be used, with potential backfill in administered activity cohorts. Patients must be 18 or older, have soft tissue sarcoma that can be measured by imaging, and meet specific health requirements, including good organ function and a positive PET scan. Each treatment cycle in the phase 1 portion of the study involves a single injection on Day 1, followed by eight weeks of monitoring. Patients have a target of four cycles of treatment, with the possibility of two more (six maximum), if their side effects are mild and their disease hasn't worsened. A Safety Review Committee (SRC) will review the data from each group in the Phase 1 portion to decide when it's safe to move to the next dose level. The SRC will also provide recommendations on timing and administered activity for backfill cohorts to gather additional safety and preliminary data on effectiveness. Patients that receive at least one treatment in the Phase 1 portion of the study, will be followed will be followed in Active (AFUP) or Long-term follow-up (LTFU). The AFUP will follow patients until confirmation of disease progression or start of subsequent anti-cancer therapy. After AFUP, the patient will enter LTFUP. Patients who discontinue with confirmed progressive disease will be monitored for LTFU via remote or onsite visits every 6 months until 5 years after the start of treatment to track long-term safety, disease progression, and overall survival. The Phase 2 portion of the study will evaluate the efficacy and safety of \[Ac225\]RTX-2358 of up to 50 patients.