ECLIPSE trial: 177Lu-PSMA-I&T extends rPFS vs hormone therapy in mCRPC

The phase 3 ECLIPSE trial (NCT05204927) has met its primary end point, showing that ¹⁷⁷Lu-PSMA-I&T (lutetium (¹⁷⁷Lu) zadavotide guraxetan) significantly extended radiographic progression-free survival (rPFS) vs hormone therapy in patients with prostate-specific membrane antigen (PSMA)-positive metastatic-castration resistant prostate cancer (mCRPC), Curium announced in a news release.¹

The investigators also plan to conduct a substudy to assess pharmacokinetic and radiation dosimetry.

“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,” said Sakir Mutevelic, MD, Curium’s Chief Medical Officer, in the news release.¹ “ECLIPSE is the first phase 3 trial investigating a 200 mCi (7.4 GBq) dose of ¹⁷⁷Lu-PSMA-I&T administered every 6 weeks for up to 6 doses, demonstrating clinical benefit, in mCRPC patients before receiving taxane-based chemotherapy. Curium will continue to work with the FDA as the clinical trial data matures, on a regulatory submission plan for this potentially important product for patients, their caregivers, and the health care providers treating prostate cancer.”

In total, the open-label, global ECLIPSE trial has enrolled over 400 adult patients with mCRPC across 51 trial sites in the United States and Europe.² To be eligible for the study, participants needed to have progressive disease, previous treatment with an androgen receptor-directed therapy, a positive PSMA-PET scan, effective castration with a serum testosterone level less than 50 ng/dL, and a life expectancy of at least 6 months.³

For the study, patients were randomly assigned 2:1 to receive 200 mCi (7.4 GBq) ¹⁷⁷Lu-PSMA-I&T or standard of care hormone therapy with either abiraterone (Zytiga) with prednisone or enzalutamide (Xtandi) per clinician judgement. Patients in the hormonal therapy arm may choose to crossover to the investigational arm if they experience radiographic progression.

The primary end point for the study is rPFS, as assessed for up to 34 weeks. Secondary end points include overall survival, progression-free survival, the rate of patients who achieve at least a 50% reduction in prostate-specific antigen (PSA), and quality-of-life measures.

The investigators also plan to conduct a substudy in 30 patients to assess pharmacokinetic and radiation dosimetry. For this analysis, participants will receive SPECT imaging following each treatment cycle.

Final completion of the ECLIPSE trial is anticipated for February 2029.

Additional news from Curium

In September, Curium announced the opening of an additional facility in the Netherlands for the production of Lutetium-177.⁴ The new facility initiallyincludes 2 production lines, with the capacity to add further lines in the future as needed.

According to the company, “Curium’s new facility will add 52 weeks of fully-redundant capacity, ensuring security of supply for patients.”

Curium also recently announced a partnership with PDRadiopharma, a wholly-owned subsidiary of PeptiDream, to further advance the clinical development, regulatory filing, and commercialization of their investigational PSMA-targeting theranostics ¹⁷⁷Lu-PSMA-I&T and ⁶⁴Cu-PSMA-I&T in Japan.⁵ Curium will continue to lead global development of the agents and support PDRadiopharma in the set-up of manufacturing lines in Japan.

Like ¹⁷⁷Lu-PSMA-I&T, ⁶⁴Cu-PSMA-I&T is also in phase 3 development. The theranostic is being assessed in the multicenter SOLAR RECUR (NCT06235099) and SOLAR STAGE (NCT06235151) trials.

References

1. Curium announces ECLIPSE trial has met primary endpoint, demonstrating a statistically significant and clinically meaningful benefit for patients with PSMA-positive metastatic castration resistant prostate cancer. News release. Curium. Published online and accessed November 13, 2024. https://www.curiumpharma.com/2024/11/13/eclipse-tiral-psma-prostate-cancer/

2. Curium completes patient enrollment of phase 3 ECLIPSE trial ahead of schedule. News release. Curium. November 21, 2023. Accessed November 13, 2024. https://www.curiumpharma.com/2023/11/21/curium-eclipse-trial-phase-3/

3. 177Lu-PSMA-I&T for metastatic castration-resistant prostate cancer. ClinicalTrials.gov. Last updated February 29, 2024. Accessed October 14, 2024. https://clinicaltrials.gov/study/NCT05204927

4. Curium announces the official opening of its new Netherlands facility for the production of Lutetium-177 – a game changer therapy isotope for cancer patients worldwide. News release. Curium. September 24, 2024. Accessed November 13, 2024. https://www.curiumpharma.com/2024/09/24/netherlands-lutetium-177/

5. Curium Announces Strategic Partnership with PeptiDream for Prostate Cancer Theranostics in Japan. News release. Curium. October 1, 2024. Accessed November 13, 2024. https://www.curiumpharma.com/2024/10/01/s-strategic-partnership-for-prostate-cancer-theranostics/