A Seamless Phase 1/2 Open-label Study to Evaluate the Safety, Determine the Maximum Tolerated Dose of Administered Activity, and Evaluate the Efficacy of the Therapeutic Radiopharmaceutical [Ac 225]-RTX-2358 in the Treatment of Relapsed or Refractory Sarcoma
The goal of this clinical trial is to learn about the safety of drug \[Ac225\]RTX-2358 and the diagnostic imaging agent \[Cu64\]LNTH-1363S. Additionally Ratio Therapeutics will learn if \[Ac225\]RTX-2358 drug is effective in treating advanced sarcoma. The main questions the study aims to answer in Phase/Part 1 of the trial are: * Is \[Ac225\]RTX-2358 tolerable or does it cause toxicities (medical problems) in patients. * What is the most tolerable dose of \[Ac225\]RTX-2358 * Does the treatment show effectiveness on advanced sarcoma Participants will: * Take drug \[Ac225\]RTX-2358 once every 8 weeks (4 cycle target; 6 cycle maximum) over a period of 12 months * Visit the clinic three times for the first week of cycle one, then once a week for the remaining 7 weeks of cycle 1 for check-ups and tests. * For cycles 2-6: patient will visit the clinic once every 2 weeks for checkups and tests * Remain in long term follow-up for a period of four additional years
• 18 years of age or older.
• History of relapse and refractory soft tissue sarcoma.
‣ Histological confirmation of sarcoma at any point since diagnosis
⁃ At least 1 prior treatment regimen
• Measurable disease as per RECIST (v1.1) for soft tissue sarcoma that is also positive on FAPi PET/CT or PET/MRI scan.
• ECOG performance status of 0 or 1.
• Adequate Organ reserve and renal function as evidenced by:
‣ Neutrophil count ≥ 1200 µL without granulocyte colony stimulating factor
⁃ Platelet count ≥ 100,000 µL
⁃ Hemoglobin ≥ 8 g/dL
⁃ Total bilirubin level ≤ 1.5 × upper limit of normal (ULN).
⁃ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN.
⁃ Calculated creatinine clearance ≥ 60 mL/min. 6. Coagulation parameters (prothrombin time, international normalized ratio and activated partial thromboplastin time) ≤ 1.5 × ULN 7. All patients (males and females of childbearing potential) must agree to practice 2 forms of highly effective contraceptive precautions to prevent pregnancy from the time consent is signed and throughout the trial.
‣ 8\. The patient or the patient's legal representative must be willing and able to provide written informed consent.