A phase 1/2 trial (NCT04886986) is currently underway to investigate the combination of 225Ac-J591 and 177Lu-PSMA-I&T in patients with metastatic castration-resistant prostate cancer (mCRPC). This study aims to determine the safety and potential efficacy of this novel therapeutic approach in a patient population with limited treatment options.
The phase 1 portion of the trial employs a dose-escalation design. Patients receive a fixed dose of 6.8 GBq of intravenous (IV) 177Lu-PSMA-I&T every three weeks, in conjunction with escalating doses of IV 225Ac-J591. The 225Ac-J591 is administered in two cycles, spaced eight weeks apart, with doses ranging from 30 to 40 KBq/kg.
Early Tolerability Data
According to Scott T. Tagawa, MD, MS, FACP, Professor of Medicine and Urology at Weill Cornell Medical College, preliminary data from the ongoing phase 1 trial indicate that 225Ac-J591 appears to be tolerable in the initial nine patients across two cohorts. No dose-limiting toxicities (DLTs) were observed in the first three patients treated in the low-dose 225Ac-J591 cohort. While no clear DLTs have been reported in the second cohort during ongoing follow-up, one patient experienced grade 3 thrombocytopenia in early follow-up.
Trial Design and Objectives
The trial is designed to assess the safety and tolerability of the 225Ac-J591 and 177Lu-PSMA-I&T combination, as well as to evaluate preliminary efficacy signals. The study includes patients with mCRPC who have progressed on standard therapies. The primary endpoint of the phase 1 portion is to determine the maximum tolerated dose (MTD) of 225Ac-J591 when combined with 177Lu-PSMA-I&T. The phase 2 portion will further evaluate the efficacy of the combination at the MTD.
Implications for mCRPC Treatment
Metastatic castration-resistant prostate cancer remains a significant clinical challenge, with limited treatment options available for patients who progress on initial therapies. The investigation of novel therapeutic strategies, such as the combination of 225Ac-J591 and 177Lu-PSMA-I&T, holds promise for improving outcomes in this patient population. Further data from this ongoing trial will be crucial in determining the potential role of this combination therapy in the treatment of mCRPC.
