Multi-dose treatment with 67Cu-SAR-bisPSMA in mCRPC shows promise

The first patient to be dosed with 2 cycles of ⁶⁷Cu-SAR-bisPSMA at 8 GBq has achieved a complete response per RECIST v1.1 criteria, announced Clarity Pharmaceuticals, the developer of the theranostic, in a news release.¹

In total, the phase 1/2a study plans to enroll up to 44 heavily pre-treated patients with advanced mCRPC across the US.

The patient received their first cycle of ⁶⁷Cu-SAR-bisPSMA as part of cohort 2 of the phase 1/2a SECuRE trial (NCT04868604), which is evaluating the agent in patients with prostate-specific membrane antigen (PSMA)-expressing metastatic castrate-resistant prostate cancer (mCRPC). The patient received the second cycle of treatment under a US FDA Expanded Access Program (EAP), which enables some patients who had shown clinical benefit during the dose escalation phase of the study to received additional cycles of ⁶⁷Cu-SAR-bisPSMA at the request of their physician.

“This was a very special moment, delivering the news to this patient that his cancer is now undetectable following the treatment with 2 doses of 8 GBq of ⁶⁷Cu-SAR-bisPSMA. After going through a number of therapies over the years with all of them having limited effect on the progression of his cancer, we have now been unable to detect any signs of his cancer, using PSA assessment, CT, and PET imaging. The safety profile of ⁶⁷Cu-SAR-bisPSMA appears to be favorable with few side effects observed following treatment, which is remarkable for a patient who was heavily pre-treated with ADT, ARPIs, chemotherapy and a PARP inhibitor,” said principal investigator Luke Nordquist, MD, FACP, in the news release.¹ Nordquist is the founder, CEO, and urologic medical oncologist at the Urology Cancer Center at XCancer in Omaha, Nebraska.

After administration of the first cycle of ⁶⁷Cu-SAR-bisPSMA, the patient achieved a prostate-specific antigen (PSA) reduction of 99.4%, going from a baseline level of 47.2 ng/mL to 0.3 ng/mL. A second cycle of ⁶⁷Cu-SAR-bisPSMA was then administered to the patient, which further reduced his PSA to undetectable levels.

CT was unable to detect any cancer and the patient demonstrated a near complete response at follow-up in November 2023. A complete response was not fully obtained due to the reduction in the size of 1 lesion missing the complete response cutoff by 2 mm at the time of imaging, though the lesion demonstrated a reduction in size from 27 mm to 12 mm.

No lesions showed PSMA uptake using ⁶⁴Cu-SAR-bisPSMA after receiving the second cycle of ⁶⁷Cu-SAR-bisPSMA.

The patients’ PSA levels remained undetectable at 6 months following the administration of the second cycle of ⁶⁷Cu-SAR-bisPSMA, confirming a complete response as assessed by CT.

Regarding safety, no adverse events related to ⁶⁴Cu-SAR-bisPSMA were reported. AEs related to ⁶⁷Cu-SAR-bisPSMA included dry mouth, altered taste, thrombocytopenia, fatigue, and anemia. Among all patients treated in the SECuRE trial to date, no dose-limiting toxicities have been reported.

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

In total, the phase 1/2a study plans to enroll up to 44 heavily pre-treated patients with advanced mCRPC across the US,² with enrollment currently ongoing for cohort 4 of the trial. Patients enrolled in cohort 4 of the study will receive multiple treatment cycles of ⁶⁷Cu-SAR-bisPSMA at the dose level of 12 GBq. Previous cohorts (1-3) had received ⁶⁷Cu-SAR-bisPSMA at ascending single-dose levels.

Nordquist concluded in the news release,¹ “We are very excited to continue working with Clarity on the SECuRE trial as it has now entered a multi-dose cohort at a dose level of 12 GBq, exploring the potential therapeutic benefit we might see from multiple doses of the product. The EAP has given us an early insight into what these benefits might look like, and we believe that ⁶⁷Cu-SAR-bisPSMA might become a best-in-class therapeutic agent once approved, providing patients with an effective treatment option with a manageable safety profile.”

References

1. Clarity update: Complete response in first patient ever treated with 2 doses of Cu-67 SAR-bisPSMA at 8GBq. News release. Clarity Pharmaceuticals. Published online and accessed April 30, 2024. https://www.claritypharmaceuticals.com/news/complete_response/

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 April 30, 2024. https://clinicaltrials.gov/study/NCT04868604