177Lu-PSMA-I&T Shows PFS Benefit in mCRPC

3D rendering of prostate cancer

The pivotal phase 3 ECLIPSE trial met its primary end point in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with ¹⁷⁷Lu-PSMA-I&T (lutetium [177Lu] zadavotide guraxetan).¹

The study demonstrated a statistically significant and clinically meaningful improvement in median radiographic progression-free survival (rPFS) in patients with prostate-specific membrane antigen (PSMA)-positive mCRPC who received up to 6 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.

“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. ECLIPSE is the first phase 3 trial investigating a 200 mCi (7.4 GBq) dose of ¹⁷⁷Lu-PSMA-I&T administered every six weeks for up to six doses, demonstrating clinical benefit, in mCRPC patients before receiving taxane-based chemotherapy,” said Sakir Mutevelic, MD, Curium’s chief medical officer, in a press release. “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 healthcare providers treating prostate cancer.”

Investigators on the multicenter, open-label, randomized ECLIPSE trial sought to evaluate ¹⁷⁷Lu-PSMA-I&T vs hormonal therapy in patients with histologically or pathologically confirmed prostate adenocarcinoma without a predominant small cell component.² Over 400 adult patients with mCRPC have been enrolled in the study across 51 trial sites in the US and Europe.

Those aged 18 years or older were enrolled in the study and were required to have had progressive disease, defined by at least 2 consecutive increases in serum/plasma PSA levels, with a minimum starting PSA of >2 ng/mL and the increases occurring at least 1 week apart. Alternatively, measurable disease progression according to RECIST 1.1 criteria or the presence of at least 2 new bone lesions per Prostate Cancer Working Group 3 criteria were acceptable.

Patients could have received no more than 1 prior ARPI in either the castration-sensitive or castration-resistant setting, with disease progression occurring during ARPI therapy. Further, a positive PSMA PET scan, as assessed by a central reader, was required, as well as effective castration, demonstrated by a serum testosterone level of <50 ng/dL.

Once enrolled, patients were randomly assigned 2:1 and treated with 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, consisting of abiraterone acetate (Zytiga) and prednisone or enzalutamide (Xtandi) alone. Upon radiographic disease progression, patients in the control arm were eligible to cross over to receive ¹⁷⁷Lu-PSMA-I&T.

The primary end point was rPFS. Secondary end points of the trial were 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 data is February 2029.

“The ECLIPSE achievement of its primary end point represents an important clinical milestone in the development of our prostate theranostic program. 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,” added Michael Patterson, chief executive officer, Curium North America, in the press release.¹ “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.”

Currently, Lutetium Lu 177 vipivotide tetraxetan (Pluvicto; formerly ¹⁷⁷Lu-PSMA-617) is the only radioligand therapy approved for the treatment of patients with prostate cancer in the US.¹

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.³ The approval was supported by findings from the international, prospective, open-label, multicenter, randomized, phase 3 VISION study (NCT03511664).⁴

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 14, 2024. https://tinyurl.com/2b6zyvjn

2. 177Lu-PSMA-I&T for metastatic castration-resistant prostate cancer. ClinicalTrials.gov. Updated October 31, 2024. Accessed November 14, 2024. https://clinicaltrials.gov/study/NCT05204927

3. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. FDA. March 23, 2022. Accessed November 14, 2024. https://tinyurl.com/bdhybp9t

4. Sartor O, de Bono J, Chi Km, et al. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021; 385(12):1091-1103. doi: 10.1056/NEJMoa2107322