60MO Theranostics in soft tissue sarcoma using a vascular disruption approach: Preliminary results of a proof-of-concept pilot study

Patients with advanced soft tissue sarcomas (STSs) have very poor prognosis and systemic chemotherapy is the mainstay of therapy. Prostate-specific membrane antigen (PSMA) is highly expressed on the neovasculature of solid tumors, including 20% of STS lesions. PSMA theranostics using Gallium-68 PSMA-11 PET including contrast-enhanced CT (PSMA PET/ceCT) and Lutetium-177 ITG PSMA radioligand therapy (PSMA RLT) could be an interesting alternative for STS patients after standard therapy. Our single center, prospective clinical trial aims to evaluate feasibility and efficacy in advanced heavily treated patients with STS. Patients with STS, progressing after standard therapy, ECOG 0-2 and a life expectancy of >3 months and adequate organ function qualify for study inclusion. Patients were screened by PSMA PET/CT and if uptake was relevant (higher than liver) were proposed to receive two standard cycles of 7400 MBq PSMA RLT in a classical six-week interval. Toxicity was noted using CTCAE v5.0 criteria, efficacy was measured by follow-up PSMA/ceCT to measure changes in PSMA uptake and according to RECIST 1.1. Secondary endpoints include dosimetry, progression-free survival (PFS), adverse events (AEs), overall survival (OS) and changes in immunological markers. Preliminary results show a high frequency of relevant PSMA uptake in sarcoma lesions of STS patients by PSMA PET/ceCT. Patients amenable for PSMA RLT did well tolerate two cycles of PSMA RLT. Efficacy analysis, toxicity and dosimetry data are currently being analyzed and will be presented at the congress. PSMA theranostics show an unexpected high number PSMA positive in PSMA PET/ceCT in STS patients. The study is ongoing and final results will be presented at the congress. It might be that PSMA RLT could be a viable alternative for STS patients after exhausting standard treatment however larger trials are needed to better understand the real value of this approach in STS patients.