Evaluation of the safety, efficacy and dosimetry of TRC003 in metastatic castration-resistant prostate cancer: A prospective, open-label, single-arm study.

5037 Background: TRC003 (also named as 225 Ac-PSMA-313) is a novel molecule of targeted alpha therapy (TAT) that administers alpha-particle radiation to cancer cells expressing Prostate Specific Membrane Antigen (PSMA). In this study, we plan to investigate preliminary safety, efficacy and dosimetry of TRC003 in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: This is a prospective, open-label, single-arm, single center study in accordance with ICH GCP guidelines. The patients with progressive PSMA-positive mCRPC who have been treated with androgen receptor pathway inhibitors (ARPIs) and/or taxane-based chemotherapy were recruited and received TRC003 treatment intravenously at 200 µCi (7.4 MBq) doses administered every 8 weeks per cycle for 4 cycles followed by expanded 4 cycle treatment if the participants continued to be benefit from the treatment. Adverse events, ORR, PSA response, bPFS, rPFS and OS were evaluated. In addition, the SPECT images were acquired with noncircular orbit, 120 project views over 360° at 4, 24, 48 and 96 hours after administration for dosimetry analysis. Results: From Feb 2024 to Jan 2026, 15 patients were included with an average age of 67.1 yr and median baseline PSA of 98.6 ng/mL. 11 (73.3%) participants received ARPI and taxane-based chemotherapies while 4 (26.7%) participants received only ARPI previously. Median baseline SUVmax and SUVmean on PSMA-PET were 32.7 (14.7-60.26) and 18.2 (9.51-34.73), respectively. A total of 63 cycles of TRC003 were administered, with a median of 4 cycles per patient. The most common AE was anemia (80%) and dry mouth (73.3%). Grade 3 treatment-related adverse events occurred as anemia (20%), lymphocytopenia (13.3%), weight loss (13.3%), thrombocytopenia (6.7%), and vomiting (6.7%). No treatment-related Grade ≥4 AE were observed. No kidney related toxicities were observed. The ORR of all patients was 45.5%, whereas the ORR reached 57.1% in the subset of patients who had received prior treatment of ARPIs and taxanes. The median tumor absorbed dose was 2.40±3.33 Gy (soft lesions: 5.03±5.51 vs bone: 1.65±2.19 Gy). The absorbed doses of kidneys, liver and spleen were 1.56±0.38, 1.07±0.19 and 0.54±0.29 Gy, respectively. The absorbed dose coefficients of tumors, kidney and liver were 0.36±0.50 (soft lesions 0.75±0.82 vs bone 0.25±0.33), 0.23±0.07, 0.16±0.03 Gy/MBq. Conclusions: TRC003 was safe and well-tolerated, and exhibited efficacy for mCRPC patients who were resistant to ARPI or chemotherapy. Overall TRC003 is a promising radiopharmaceutical agent for the treatment of mCRPC. Clinical trial information: ChiCTR2400083275.