A recent phase 3 clinical trial, ECLIPSE, has shown that 177Lu-PSMA-I&T (lutetium (177Lu) zadavotide guraxetan) significantly prolongs radiographic progression-free survival (rPFS) in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) compared to standard hormone therapy in patients previously treated with an androgen receptor pathway inhibitor (ARPI) compared to a change in ARPI. This is a significant finding as it offers a new treatment option for patients with this advanced form of prostate cancer.

The ECLIPSE Trial

The ECLIPSE trial (NCT05204927) is an open-label, global study that enrolled over 400 adult patients with mCRPC. Patients, previously treated with an ARPI were randomized 2:1 to receive either 177Lu-PSMA-I&T or standard hormone therapy (abiraterone with prednisone or enzalutamide). The primary endpoint was rPFS, assessed for up to 34 weeks. Secondary endpoints included overall survival, progression-free survival, PSA response rate, and quality-of-life measures.

NOTE: at the moment I don’t know which ARPIs were used at earlier stage for the patients involved in the study (apalutamide or darolutamide or…)

Key Findings and Implications

The trial met its primary endpoint, demonstrating that 177Lu-PSMA-I&T significantly extended rPFS compared to hormone therapy. This finding has the potential to change the treatment landscape for mCRPC. Curium, the company developing 177Lu-PSMA-I&T, is working with the FDA on a regulatory submission plan based on these positive results.
The trial also includes a substudy to assess pharmacokinetics and radiation dosimetry using SPECT imaging. This data will further enhance our understanding of the treatment and its effects.

Source.