FDA grants fast track designation to 67Cu-SAR-bisPSMA for mCRPC

The FDA has awarded a fast track designation (FTD) to ⁶⁷Cu-SAR-bisPSMA for the treatment of patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have previously been treated with an androgen receptor pathway inhibitor (ARPI), Clarity Pharmaceuticals announced in a news release.¹

The SECuRE trial remains ongoing.

FTD is awarded to novel agents that are intended to treat or prevent serious conditions and have the potential to address an unmet medical need. With this designation, the development process for ⁶⁷Cu-SAR-bisPSMA can benefit from more frequent engagement with the FDA, eligibility for accelerated approval, and priority review.

Clarity’s diagnostic, ⁶⁴Cu-SAR-bisPSMA, was previously granted FTDs for PET imaging of PSMA-positive lesions in patients with biochemical recurrence (BCR) of prostate cancer following initial definitive therapy and for PET imaging of PSMA-positive prostate cancer lesions in patients with suspected metastasis who are candidates for initial definitive therapy.

“The granting of FTDs by the US FDA for 3 distinct indications in prostate cancer that we are aiming to address with this product is testament to the incredible work of our team and collaborators,” said Alan Taylor, Clarity’s executive chairperson, in the news release.¹ “This latest FTD will allow us flexibility to develop ⁶⁷Cu-SAR-bisPSMA in both pre- and post-chemotherapy patients in the mCRPC setting, with initial focus on the largest market segment. The SECuRE study will also provide invaluable information on the potential of ⁶⁷Cu-SAR-bisPSMA to be combined with enzalutamide and other ARPIs in future, creating opportunities for the broader use of ⁶⁷Cu-SAR-bisPSMA in those patients with such high unmet medical need.”

The FTD is backed by preliminary data from the ongoing phase 1/2a SECuRE trial (NCT04868604), which is evaluating the safety and efficacy of ⁶⁷Cu-SAR-bisPSMA in patients with mCRPC. In the study, ⁶⁴Cu-SAR-bisPSMA is used to visualize PSMA-expressing lesions to select candidates for therapy with ⁶⁷Cu-SAR-bisPSMA. The first 3 cohorts in the trial evaluated ascending single-dose levels of ⁶⁷Cu-SAR-bisPSMA and have been successfully completed.

Across all 15 patients dosed in these 3 cohorts, no dose-limiting toxicities were reported, and no adverse events (AEs) related to ⁶⁴Cu-SAR-bisPSMA were observed. AEs related to ⁶⁷Cu-SAR-bisPSMA were generally grade 1 or 2. The most common AE was mild dry mouth, reported in 33.3% of participants.

The study is now progressing through cohort 4 of the trial, in which patients are receiving multiple doses (range, 2-4) of the highest dose level (12 GBq) of ⁶⁷Cu-SAR-bisPSMA. Three participants are currently in the safety and efficacy follow-up phase after receiving 2 doses of treatment, after which the safety review committee plans to meet (expected in March 2025).

Efficacy data from the trial has been encouraging so far. Overall, 73% of patients have shown reductions in prostate-specific antigen (PSA) levels. The majority of patients who experienced an increase in PSA were enrolled in the lowest dose cohort (4 GBq) in the trial.

Additionally, 45% of patients across all 4 cohorts have experienced a PSA reduction greater than 50%. In cohorts 2, 3, and 4 specifically, (which assessed 8 and 12 GBq single doses and 12 GBq multi-doses, respectively), nearly 75% of patients experienced a PSA reduction greater than 35%, and nearly half of the patients have experienced a PSA reduction of at least 80%.

The greatest PSA decline in cohort 4 of the trial was 98% (from a baseline of 157.4 ng/mL) in a patient who had failed multiple prior lines of therapy. The patient achieved a radiographic partial response per RECIST v1.1 with a 60.6% reduction in tumor volume on preliminary PSMA-PET imaging.

SECuRE design

Overall, the multi-center phase 1/2a SECuRE trial is evaluating the safety and efficacy of ⁶⁷Cu-SAR-bisPSMA for the treatment of patients with mCRPC.

In total, the study has enrolled approximately 44 heavily pre-treated patients with mCRPC across the US and Australia.² Patients enrolled in cohort 4 of the study received multiple treatment cycles of ⁶⁷Cu-SAR-bisPSMA (range, 2 to 4) at the dose level of 12 GBq. Previous cohorts (1-3) had received ⁶⁷Cu-SAR-bisPSMA at ascending single-dose levels.

Among all patients enrolled in the study, 77% had bone metastasis, and 59% of patients had received 3 or more lines of prior therapy. The median PSA at baseline was 112.86 ng/mL (range, 0.1-1503.1).

Additional information on SECuRE

The SECuRE trial remains ongoing.The protocol for the trial was recently amended to increase the number of participants in the cohort expansion phase from 14 to 24. Patients are eligible for inclusion if they have mCRPC and have not yet received chemotherapy.

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 with enzalutamide led to enhanced anti-cancer activity and improved clinical outcomes in mCRPC.³

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

REFERENCES

1. 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. Published online and accessed February 19, 2025. https://www.claritypharmaceuticals.com/news/ftd-67cu-sarbispsma/

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 February 19, 2025. https://clinicaltrials.gov/study/NCT04868604

3. Emmett L, Subramaniam S, Crumbaker M, et al. Enzalutamide and 177Lu-PSMA-617 in poor-risk, metastatic, castration-resistant prostate cancer (mCRPC): A randomised, phase II trial: ENZA-p (ANZUP 1901). Presented at 2023 European Society for Medical Oncology Congress. Madrid, Spain. Ann Oncol. Volume 34, S1325. LBA84