FDA Grants Fast Track Designation to 67Cu-SAR-bisPSMA in mCRPC
The FDA has granted fast track status to 67Cu-SAR-bisPSMA for metastatic prostate cancer that is resistant to hormone therapy after prior treatment, based on SECuRE trial data.
- The FDA granted fast track designation (FTD) to 67Cu-SAR-bisPSMA for treating adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been previously treated with androgen receptor pathway inhibition (ARPI).
- This marks the third FTD for the SAR-bisPSMA molecule within the past 6 months.
- Preliminary data from the ongoing phase 1/2a SECuRE trial (NCT04868604) support this designation.
The FDA has granted FTD to 67Cu-SAR-bisPSMA for the treatment of adult patients with PSMA-positive mCRPC who have previously received ARPI.1
This marks the third FTD for the SAR-bisPSMA molecule within the past 6 months. Specifically, this FDA designation follows previous ones for the diagnostic 64Cu-SAR-bisPSMA in patients with suspected prostate cancer metastasis eligible for initial definitive therapy and in patients with biochemical recurrence post-definitive therapy.
"Receiving 3 fast track designations for the 1 molecule, SAR-bisPSMA, within the last 6 months is an incredible achievement for Clarity, highlighting how impressive our science and development are, the significance of the diagnostic and therapeutic data so far, and the high unmet need for better therapies and diagnostics in prostate cancer,” said Alan Taylor, PhD, executive chairperson of Clarity Pharmaceuticals, in a press release.
Promising preliminary data from the ongoing phase 1/2a SECuRE trial support this FTD. The trial is evaluating the safety and efficacy of 67Cu-SAR-bisPSMA in patients with PSMA-positive mCRPC who have progressed on prior ARPI therapy. Early results demonstrate significant PSA reductions across various dose levels. Notably, 73% of evaluable patients across all dose-escalation cohorts experienced a decrease in PSA levels, with 45% achieving reductions greater than 50%, even with a single dose of 67Cu-SAR-bisPSMA at either 4, 8, or 12 GBq.
Further analysis of patients in cohorts 2, 3, and 4, who received single 8-GBq, single 12-GBq, and 12-GBq multi-dose regimens, respectively, revealed that nearly 75% of patients experienced PSA reductions exceeding 35%, and almost half achieved reductions of at least 80%.
The initial dose-escalation phase (n = 15) showed a favorable safety profile. No dose-limiting toxicities were observed, and treatment-related adverse events were primarily grade 1 or 2, with the most common being grade 1 dry mouth (33.3%).
“The dual-targeted bisPSMA molecule was developed at the benchtop of Australian science with the intent of overcoming the shortfalls of the current generation of PSMA-targeting products. It was optimized with 2 PSMA ligands, which increases not only the amount of product in the lesions, but also how long the product is retained in the lesions over time, making it an ideal candidate for both diagnosis and therapy. The clinical data in both diagnostic and therapeutic indications that we are generating is remarkable, confirming the results that we initially saw in preclinical development,” added Taylor in the press release.1
3D rendered medically accurate illustration of prostate cancer: © SciePro - stock.adobe.com
Methods and Design of the SECuRE Trial
SECuRE, a multicenter, single-arm, nonrandomized, open-label, phase 1/2a study, is evaluating 67Cu-SAR-bisPSMA for the treatment of patients aged 18 years or older with mCRPC with documented disease progression.2 Patients must have received previous treatment with androgen deprivation therapy and at least 1 ARPI, have a positive 64Cu-SAR-bisPSMA PET/CT scan, an ECOG performance status of 0 to 2, a life expectancy of more than 6 months, adequate organ function, and at least 1 metastatic lesion.
The dose-escalation phase involves up to 2 administrations of 67Cu-SAR-bisPSMA, with 2 doses at the recommended phase 2 dose (RP2D) being administered during cohort expansion. According to the press release, a recent protocol amendment has increased the number of patients in the cohort expansion phase of the trial to 24 from 14.1 A subset of patients will also receive the combination of 67Cu-SAR-bisPSMA with enzalutamide (Xtandi).
The primary end points of the study include biodistribution and dosimetry of 64Cu-SAR-bisPSMA, determination of the maximum tolerated dose and RP2D of 67Cu-SAR-bisPSMA, and preliminary efficacy assessment.2
Enrollment for cohort 4 is now complete, with 3 patients having received 2 doses of the study treatment and currently undergoing safety and efficacy follow-up. A safety review committee meeting is anticipated in March 2025 following this follow-up period.
“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,” added Taylor in the press release.1
REFERENCES:
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 February 21, 2025. https://tinyurl.com/36v768eb
64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for identification and treatment of PSMA-expressing metastatic castrate resistant prostate cancer (SECuRE). ClinicalTrials.gov. Updated March 27, 2024. Accessed February 21, 2025. https://clinicaltrials.gov/study/NCT04868604
