Cu-67 SAR-bisPSMA Granted Fast Track Designation for Metastatic CRPC

Results from the phase 1/2a SeCuRE trial support the FDA decision for patients with metastatic castration-resistant prostate cancer.

The FDA has granted ⁶⁷Cu-SAR-bisPSMA fast track designation for the treatment of adult patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (CRPC) who received prior androgen receptor pathway inhibition (ARPI), according to a press release from the drug’s developer, Clarity Pharmaceuticals.¹

Support for the decision comes from data from the phase 1/2a SECuRE trial (NCT04868604), which is investigating the safety and efficacy of the agent as a treatment for patients with metastatic CRPC. Of note, the initial 3 cohorts of the dose escalation phase were completed, and no dose-limiting toxicities (DLTs) were reported in the 15 patients dosed. Most adverse effects (AEs) related to ⁶⁷Cu-SAR-bisPSMA were grades 1 or 2, with the most commonly reported AE being dry mouth (33%).

Furthermore, preliminary efficacy data revealed that in this patient population, 73% of patients showed a PSA level reduction, with the majority of patients experiencing PSA level increases assigned to the lowest dose cohort of 4 GBq of ⁶⁷Cu-SAR-bisPSMA. Additionally, PSA reductions of greater than 50% were observed in 45% of evaluable patients, despite most patients only receiving a single dose of ⁶⁷Cu-SAR-bisPSMA at the 4, 8, and 12 GBq levels.

“Receiving 3 [fast track designations] for the one 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,” Alan Taylor, PhD, executive chairperson of Clarity Pharmaceuticals, said in the news release on the FDA decision.¹ “These designations will allow us to work closely with the FDA to facilitate the development process and accelerate the approval of what could become best-in-class therapy and diagnostic agents, and our team and collaborators are committed to making this our priority in order to achieve our ultimate goal of improving treatment outcomes for [patients] with cancer.”

Patients in the phase 1/2a SECuRE trial were assigned to receive ⁶⁴Cu-SAR-bisPSMA at a dose level of 200 MBq followed by an additional 2 doses of 200 MBq ⁶⁴Cu-SAR-bisPSMA in the dose escalation phase.² Furthermore, in the cohort expansion phase, 3 doses of 200 MBq ⁶⁴Cu-SAR-bisPSMA were administered.

Patients then received⁶⁷Cu-SAR-bisPSMA, and were given either 4, 8, or 12 GBq for 1 or 2 doses depending on cohort allocation in a dose escalation phase. Furthermore, in a dose expansion phase, patients received 2 doses of ⁶⁷Cu-SAR-bisPSMA at the recommended dose level found through dose escalation.

Most patients enrolled on the trial had bone metastases (77%) and were heavily pretreated, with 59% of patients receiving at least 3 lines of prior therapy. Furthermore, a median PSA level of 112.86 ng/mL (range, 0.1-1503.1) was reported.

The trial assessed the biodistribution and dosimetry of ⁶⁴Cu-SAR-bisPSMA, maximum tolerated dose of ⁶⁷Cu-SAR-bisPSMA, and recommended dose of ⁶⁷Cu-SAR-bisPSMA. Additionally, PSA and radiographic response in ⁶⁷Cu-SAR-bisPSMA was assessed, as well as safety.

Patients are receiving ongoing treatment in the highest dose cohort of multiple 12GBq doses of⁶⁷Cu-SAR-bisPSMA. Recruitment into this cohort is complete and the remaining patients are undergoing safety and efficacy follow-up after receiving the second therapy dose. Of note, 1 patient experienced a PSA reduction of 98% from a baseline of 157.4 ng/mL after experiencing disease progression following multiple lines of therapy, including an androgen deprivation therapy (ADT), ARPI, and an investigational agent.

Following the completion of follow-up for cohort 4, a safety review committee meeting is planned for March 2025.

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. February 19, 2025. Accessed February 20, 2025. https://tinyurl.com/yc2n4525
2. 64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for identification and treatment of PSMA-expressing metastatic castrate resistant prostate cancer (SECuRE) (SECuRE). ClinicalTrials.gov. Updated March 27, 2024. Accessed February 20, 2025. https://tinyurl.com/4fv5wpbd