Trial of 64Cu/67Cu-SAR-bisPSMA in mCRPC progresses to dose expansion phase

The phase 1/2 SECuRE trial (NCT04868604) has completed the dose escalation phase and is progressing to the dose expansion phase (phase 2), Clarity Pharmaceuticals announced in a news release.¹

⁶⁷Cu-SAR-bisPSMA was granted a fast track designation by the FDA last month.

Overall, the study is evaluating the safety and efficacy of ⁶⁴Cu/⁶⁷Cu-SAR-bisPSMA in the treatment of men with metastatic castration-resistant prostate cancer (mCRPC). In the study, ⁶⁴Cu-SAR-bisPSMA is being used to visualize prostate-specific membrane antigen-expressing lesions to select candidates for therapy with ⁶⁷Cu-SAR-bisPSMA.

Based on data from the phase 1 dose expansion phase, the safety review committee recommended that the phase 2 portion proceed with the 8 GBq dose, with an increase in the number of cycles from up to 4 to up to 6. Cohort 2 (assessing the 8 GBq dose) had the highest rate of PSA response in the trial, and all participants achieved disease control. Two treatment-related adverse events (AEs) were reported in 1 patient (grade 1 dry mouth and altered taste and grade 2 fatigue), and no hematological toxicity was reported.

“Dose escalation trial design has not been routinely used in other [radioligand therapy] studies,” explained Clarity’s executive chairperson, Alan Taylor, PhD, in the news release.¹ “By pioneering this approach with the SECuRE trial, Clarity was looking to systematically evaluate the safety of ⁶⁷Cu-SAR-bisPSMA in the context of its therapeutic effect. By gradually increasing the dose from one cohort to the next, we have minimized the risk of AEs and established a favorable safety profile for patients, while also demonstrating that ⁶⁷Cu-SAR-bisPSMA is effective.”

Overall, the dose escalation phase of the trial was comprised of 4 cohorts. Patients in cohorts 1-3 received ⁶⁷Cu-SAR-bisPSMA at ascending single-dose levels (4GBq, 8Gbq, and 12GBq, respectively), and patients in cohort 4 received multiple treatment cycles of ⁶⁷Cu-SAR-bisPSMA (range, 2 to 4) at the dose level of 12 GBq.

Across all cohorts, 68% of patients achieved a reduction in prostate-specific antigen (PSA) levels, and 78% of patients achieved disease control (complete response + partial response + stable disease) per radiographic assessment. In cohort 4 of the trial, evaluating multi-dose treatment, PSA reductions of at least 80% have been observed in 3 cases so far. One patient has achieved a complete response per RECIST v1.1.

The majority of AEs in the trial have been grade 1-2. The most common hematological AEs were anemia and thrombocytopenia. One dose-limiting toxicity was observed in a patient in cohort 4 of the study.

The investigators also assessed 13 patients in the trial who had not received chemotherapy. Among these patients, 69.2% had bone metastases and 46.2% had received at least 3 lines of prior therapy. The median PSA was 42.41 ng/dL (range, 0.1-182.4).

Overall, 12/13 of these patients achieved a PSA reduction greater than 35%, 8/13 (61.5%) achieved a PSA reduction of greater than 50%, and 6/13 (46.2%) achieved a PSA reduction of at least 80%. Among those with measurable disease at baseline (n = 12), disease control was achieved in 92% of patients. In total, 1 patient achieved a complete response, 2 patients achieved a partial response, and 8 patients achieved stable disease.

The safety profile among these patients was comparable to that seen in overall patient population.

Following these findings, the protocol for the trial was amended to include participants in the pre-chemotherapy setting. The amendment also increased the number of participants in the cohort expansion phase from 14 to 24.

A subset of these patients are expected to receive ⁶⁷Cu-SAR-bisPSMA in combination with enzalutamide (Xtandi). The decision to assess ⁶⁷Cu-SAR-bisPSMA in combination with enzalutamide was made based on positive findings from the Enza-p trial (NCT04419402), which demonstrated that adaptive dosing of ¹⁷⁷Lu-PSMA-617 (Pluvicto) in combination with enzalutamide led to enhanced anti-cancer activity and improved clinical outcomes in patients with mCRPC.^3,4

Final results from the SECuRE trial are expected in September 2026.

⁶⁷Cu-SAR-bisPSMA was granted a fast track designation by the FDA last month, which was supported by interim data from the phase 1/2 SECuRE trial.⁴

REFERENCES

1. SECuRE trial update: 92% of pre-chemo participants experience greater than 35% drop in PSA levels across all cohorts. Cohort Expansion Phase commences. News release. Clarity Pharmaceuticals. Published online and accessed March 5, 2025. https://www.claritypharmaceuticals.com/news/secure-update/

2. 64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for identification and treatment of PSMA-expressing metastatic castrate resistant prostate cancer (SECuRE) (SECuRE). ClinicalTrials.gov. Last updated March 27, 2024. Accessed March 5, 2025. https://clinicaltrials.gov/study/NCT04868604

3. Emmett L, Subramaniam S, Crumbaker M, et al. Overall survival and quality of life with [177Lu]Lu-PSMA-617 plus enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer (ENZA-p): secondary outcomes from a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2025 Feb 12:S1470-2045(25)00009-9. doi:10.1016/S1470-2045(25)00009-9

4. Clarity receives US FDA Fast Track Designation for the treatment of metastatic castration-resistant prostate cancer patients with Cu-67 SAR-bisPSMA. News release. Clarity Pharmaceuticals. February 19, 2025. Accessed March 5, 2025. https://www.claritypharmaceuticals.com/news/ftd-67cu-sarbispsma/