First-in-human evaluation of 225Ac-PSMA-Trillium™ (BAY 3563254; 225Ac felivotide mopaxetan) in metastatic castration-resistant prostate cancer: the phase 1 PAnTHA study

Abstract

Abstract Prolonged survival demonstrated with the alpha-emitting radionuclide radium-223 dichloride and the prostate-specific membrane antigen (PSMA)-targeting radioligand [ 177 Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC) provides a rationale for combining the potent alpha-emitter actinium-225 ([ 225 Ac]Ac) with a PSMA-targeting moiety. We report the dose escalation part (n=50) of the phase 1 PAnTHA study (NCT06217822) evaluating safety and efficacy of [ 225 Ac]Ac-PSMA-Trillium (BAY 3563254; 225 Ac felivotide mopaxetan) in heavily pretreated patients with mCRPC. [ 225 Ac]Ac-PSMA-Trillium was relatively well tolerated with no dose-limiting toxicities. Xerostomia occurred in 86% of patients (grade 1: 56%, grade 2: 30%) and did not cause treatment discontinuation. Overall, 44% had grade 3 treatment-emergent adverse events, most commonly lymphopenia (22%) and anemia (6%). Two patients had grade 4 lymphopenia. Finally, 62% achieved PSA50, with respective overall response and disease control rates of 50% and 83%. [ 225 Ac]Ac-PSMA-Trillium has a manageable safety profile and strong preliminary efficacy in heavily pretreated patients with mCRPC.