Abstract CT224: Preliminary efficacy and safety results from the (TATCIST) trial: A PSMA-directed targeted alpha therapy with FPI-2265 (225Ac-PSMA-I&T) for the treatment of metastatic castration-resistant prostate cancer (mCRPC)

Abstract INTRODUCTION: Targeted α therapy (TAT) in mCRPC is a rapidly advancing class of radiotherapeutics that can effectively deliver potent and local radiation selectively to cancer cells while sparing the surrounding normal cells. Retrospective studies of 225Ac PSMA-RLT (radioligand therapy), have shown promise in pts with mCRPC, where activity correlates with disease characteristics and prior therapies. FPI-2265 (225Ac-PSMA-I de-escalation in cycle 2 and beyond is allowed. Proportion of pts with PSA ≤50%, maximum %PSA decrease, and safety and tolerability of FPI-2265 were assessed. RESULTS: At the time of the data cut (30Jan2024) 30 pts have received ≥1 dose FPI-2265, with 25 pts having ≥12 weeks follow up. For this analysis, 21 pts were evaluable for safety and 20 pts were evaluable for PSA response: 4 pts with superscan were excluded and 1 pt was excluded due to uninterpretable PSA data. In general, pts were heavily pretreated in terms of prior lines of therapy. Most pts (17/21 81%) had received a prior taxane, including 8 pts who received ≥2 lines of taxanes. Eight pts received prior 177Lu PSMA-RLT (Lu). PSA50 was achieved in 10/20 pts (50%) ; In a subset of pts with the baseline PSMA SUVmean 6 (n=13 overall; post-Lu, n=6), PSA50 was achieved in 9 pts (69%). Treatment-related adverse events (TRAEs) included dry mouth (18/21 86%), fatigue (10/21 48%) dry eye (6/21 28%), and anemia (6/21 28%). All were Grade 1-2 in severity, expect anemia Grade 3 which was observed in (5/21 24%). Other Grade 3 TRAEs included decreased platelet count (3/21 14%). No Grade 4 or 5 TRAEs were reported. Dry mouth was primarily Grade 1 (13/21 62%) with only 5 patients (24%) experiencing Grade 2 dry mouth; there were no related discontinuations. CONCLUSION: Preliminary efficacy and safety data as of 30Jan24 suggest that FPI-2265 is active in heavily pretreated pts with progressive mCRPC, including pts who received prior Lu therapy. Higher PSMA SUVmean was associated with improved PSA responses, Safety and tolerability were consistent with other published studies of 225Ac-PSMA-RLTs. These initial results support further investigation of FPI-2265 and a new phase 2/3 trial will begin enrolling soon. Citation Format: Ebrahim S. Delpassand, Mohammad Jawed Hashmi, Julia Kazakin, Omer Nawaz, Gabriella Garufi, Joanne Schindler, Luke Nordquist. Preliminary efficacy and safety results from the (TATCIST) trial: A PSMA-directed targeted alpha therapy with FPI-2265 (225Ac-PSMA-I Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr CT224.