177Lu-PSMA-I&T Meets rPFS End Point in PSMA+ mCRPC

Treatment with the prostate-specific membrane antigen (PSMA)–targeted radioligand ¹⁷⁷Lu-PSMA-I&T (lutetium [¹⁷⁷Lu] zadavotide guraxetan) led to a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) compared with hormonal therapy in patients with metastatic castration-resistant prostate cancer (mCRPC), meeting the primary end point of the phase 3 ECLIPSE trial (NCT05204927).¹

The study population included patients with mCRPC who were previously treated with an androgen receptor pathway inhibitor (ARPI). During the study, patients were randomly assigned to receive ¹⁷⁷Lu-PSMA-I&T or a different ARPI. Notably, the study did not allow for prior chemotherapy in the mCRPC setting.²

“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,” Sakir Mutevelic, MD, chief medical officer of Curium, stated in a 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 [patients with] mCRPC before receiving taxane-based chemotherapy. Curium will continue to work with the FDA as the clinical trial data mature on a regulatory submission plan for this potentially important product for patients, their caregivers, and the health care providers treating prostate cancer.”

Lutetium Lu 177 vipivotide tetraxetan (Pluvicto; formerly ¹⁷⁷Lu-PSMA-617) is the only radioligand therapy currently approved in the United States for the treatment of patients with prostate cancer. In March 2022, the FDA approved the agent for adult patients with PSMA-positive mCRPC who have previously received other anticancer therapies, such as an ARPI and taxane-based chemotherapy.³

ECLIPSE was a multicenter, open-label, randomized study that evaluated ¹⁷⁷Lu-PSMA-I&T vs hormonal therapy in patients at least 18 years of age with histologically or pathologically confirmed prostate adenocarcinoma without a predominant small cell component.2 Patients needed to have progressive disease defined as serum/plasma PSA progression with 2 consecutive increases in PSA at least 1 week apart with a minimum start value of more than 2 ng/mL; and/or measurable disease progression per RECIST 1.1 criteria or the presence of at least 2 new bone lesions per Prostate Cancer Working Group 3 criteria.

No more than 1 prior APRI administered in the castration-sensitive or castration-resistant setting was allowed, and disease progression during ARPI therapy was required. A positive PSMA PET scan per central reader assessment and effective castration with a serum testosterone level of less than 50 ng/dL were also required

Prior radioligand therapy or radium-223 (Xofigo) were not permitted. Previous chemotherapy in the CRPC setting was not allowed; however, prior docetaxel given in the hormone-sensitive setting was permitted if patients did not receive more than 6 doses, received the final chemotherapy dose more than 1 year before enrollment, and did not experienced disease progression on docetaxel. Other key exclusion criteria consisted of an ECOG performance status of 2 or higher; known homologous recombination repair gene mutations; and inadequate organ and bone marrow function.

Investigators randomly assigned patients in a 2:1 fashion to receive 200 mCi (7.4 GBq) of ¹⁷⁷Lu-PSMA-I&T once every 6 weeks for up to 6 doses; or investigator’s choice of hormonal therapy, which included abiraterone acetate (Zytiga) plus prednisone or enzalutamide (Xtandi) monotherapy.^1,2 Notably, patients in the control arm were permitted to cross over to receive ¹⁷⁷Lu-PSMA-I&T upon radiographic disease progression.²

Along with the primary end point of rPFS, secondary end points included overall survival, time to second radiographic progression (rPFS2), 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 ECLIPSE achievement of its primary end point represents an important clinical milestone in the development of our prostate theranostic program,” Michael Patterson, chief executive officer of Curium North America, added in a news release.1 “This underscores Curium’s continued commitment and focus on nuclear medicine diagnostics and therapeutics. Further, the announcement of the opening of Curium’s Netherlands facility for the production of ¹⁷⁷Lutetium in September 2024 bolsters Curium’s supply chain and ensures manufacturing reliability. 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.”

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. November 13, 2024. Accessed November 13, 2024. https://www.curiumpharma.com/2024/11/13/eclipse-tiral-psma-prostate-cancer/
2. 177Lu-PSMA-I&T for metastatic castration-resistant prostate cancer. ClinicalTrials.gov. Updated October 31, 2024. Accessed November 13, 2024. https://clinicaltrials.gov/study/NCT05204927
3. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. FDA. March 23, 2022. Accessed November 13, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer