Dose expansion begins in phase 1/2 trial of 67Cu-SAR-bisPSMA in mCRPC

The first patient has been dosed in the dose expansion phase of the phase 1/2 SECuRE trial (NCT04868604), which is evaluating the safety and efficacy of ⁶⁴Cu/⁶⁷Cu-SAR-bisPSMA for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC).¹

⁶⁷Cu-SAR-bisPSMA was granted a fast track designation by the FDA in February 2025.

The dose expansion phase of the study is assessing outcomes with ⁶⁷Cu-SAR-bisPSMA at a dose level of 8 GBq, which was selected following a recommendation from the safety review committee (SRC). The SRC also suggested that the phase 2 portion of the trial increase the number of cycles from up to 4 to up to 6.

Participants in the study will be enrolled across clinical trial sites in the US and Australia.

The first patient in the trial will be receiving ⁶⁷Cu-SAR-bisPSMA in combination with enzalutamide (Xtandi), made possible by a recent protocol amendment to the trial. The decision to assess this combination 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.^2,3

The amended protocol for the trial also included a focus on patients with mCRPC in the pre-chemotherapy setting and increased the number of participants in the cohort expansion phase from 14 to 24.

"With the latest protocol amendments ensuring that we are utilizing the most recent advances and knowledge in the radiopharmaceutical space, we continue to be driven by the highest standards of clinical trial management and research,” said Alan Taylor, PhD, Executive Chairperson for Clarity, in the news release.¹ “At Clarity, we are committed to working with various key opinion leaders in the field and incorporating the most recent findings into our study design to maximize the probability of clinical trial success and positive patient outcomes. As a result, we are focused on bringing ⁶⁷Cu-SAR-bisPSMA to earlier lines of prostate cancer therapy, especially in the pre-chemotherapy setting, where we have seen very promising safety and efficacy to date. We are also investigating the benefits of combination therapy, where SECuRE participants are being treated with ⁶⁷Cu-SAR-bisPSMA and enzalutamide based on the results from Prof Emmett's Enza-p trial and in consultation with global thought leaders in the prostate cancer space.”

In the news release, the company also reported, “In preparation for the cohort expansion phase, Clarity rolled out its improved ⁶⁷Cu-SAR-bisPSMA product formulation. The enhanced formulation allows for room temperature stability, supply and scalability, which are essential for late-stage clinical trials and streamlined commercial-scale manufacture.”

⁶⁷Cu-SAR-bisPSMA was granted a fast track designation by the FDA in February 2025, which was supported by interim data from the phase 1/2 SECuRE trial.⁴

Data from phase 1

Overall, the dose escalation phase of the trial was comprised of 4 cohorts.² 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. Among all patients, 77.3% had bone metastases at baseline, and 63.6% of patients had received at least 3 lines of prior therapy. The median prostate-specific antigen (PSA) level was 112.86 ng/dL (range, 0.1 to 1503.1 ng/dL).

Across all cohorts, 68% of patients achieved a reduction in 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% had been observed in 3 cases at the time of data report. One patient had 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, 92% (12 of 13) of patients achieved a PSA reduction greater than 35%, 61.5% (8 of 13) achieved a PSA reduction of greater than 50%, and 46.2% (6 of 13) achieved a PSA reduction of at least 80%. Among those with measurable disease at baseline (n = 12), disease control was achieved in 92% (11 of 12) of patients who had measurable disease at baseline. 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.

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

REFERENCES
1. SECuRE trial update: First patient treated in the Phase II Cohort Expansion. News release. Clarity Pharmaceuticals. Published online and accessed April 15, 2025. https://www.claritypharmaceuticals.com/news/secure-fp-phase2/

2. 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/

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/