The Phase 3 ECLIPSE trial has demonstrated that 177Lu-PSMA-I&T (lutetium [177Lu] zadavotide guraxetan) significantly improves radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer (mCRPC). The study, a multicenter, open-label, randomized trial, compared 177Lu-PSMA-I&T to hormonal therapy in over 400 patients across the US and Europe.
The trial's primary endpoint was met, revealing a statistically significant and clinically meaningful improvement in median rPFS in patients with prostate-specific membrane antigen (PSMA)-positive mCRPC who received up to six doses of 200 mCi (7.4 GBq) of 177Lu-PSMA-I&T. This benefit was observed in patients who had previously been treated with an androgen receptor pathway inhibitor (ARPI) when compared with those who received a change in ARPI treatment.
Trial Design and Patient Population
The ECLIPSE trial enrolled patients with histologically or pathologically confirmed prostate adenocarcinoma without a predominant small cell component. Participants were required to have progressive disease, defined by at least two consecutive increases in serum/plasma PSA levels, with a minimum starting PSA of >2 ng/mL. Patients could have received no more than one prior ARPI, with disease progression occurring during ARPI therapy. A positive PSMA PET scan was also required.
Patients were randomized 2:1 to receive either 200 mCi (7.4 GBq) of 177Lu-PSMA-I&T every six weeks for up to six doses or investigator’s choice of hormonal therapy (abiraterone acetate and prednisone or enzalutamide alone). Upon radiographic disease progression, patients in the control arm were eligible to cross over to receive 177Lu-PSMA-I&T.
Endpoints and Further Analysis
The primary endpoint of the trial was rPFS. Secondary endpoints included overall survival, time to second radiographic progression, PFS, PFS2, the rate of patients with at least a 50% reduction in PSA from baseline, time to first symptomatic skeletal event, time to soft tissue progression, time to chemotherapy, and quality of life. The estimated study completion date is February 2029.
Sakir Mutevelic, MD, Curium’s chief medical officer, stated, “This is a significant accomplishment for Curium, demonstrating in the pivotal confirmatory ECLIPSE trial a statistically significant and clinically meaningful benefit of PSMA-targeted radioligand therapy with 177Lu-PSMA-I&T for patients with mCRPC.”
Current Landscape and Future Implications
Currently, Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) is the only radioligand therapy approved for the treatment of patients with prostate cancer in the US. The FDA approved Lutetium Lu 177 vipivotide tetraxetan in March 2022 for adult patients with PSMA-positive mCRPC who have previously received other anticancer therapies, including an ARPI and taxane-based chemotherapy. The approval was supported by findings from the Phase 3 VISION study.
Michael Patterson, chief executive officer, Curium North America, added, “The ECLIPSE achievement of its primary end point represents an important clinical milestone in the development of our prostate theranostic program...Curium will continue to work to fulfill its mission of redefining the experience of cancer through our trusted legacy in nuclear medicine by ensuring unrestricted access to this important product, if approved.”
