Multi-dose phase of 64Cu/67Cu-SAR-bisPSMA study begins in mCRPC

Updated data from the phase 1/2a SECuRE trial (NCT04868604) show safety and preliminary efficacy of ⁶⁴Cu/⁶⁷Cu-SAR-bisPSMA in patients with metastatic castrate-resistant prostate cancer (mCRPC) who received single-dose administration of the theranostic at the highest dose level of 12 GBq (cohort 3), announced Clarity Pharmaceuticals, the developer of the agent, in a news release.¹

Participants enrolled in cohort 4 will receive multiple treatment cycles of ⁶⁷Cu-SAR-bisPSMA at the dose level of 12 GBq.

According to Clarity, the Safety Review Committee has recommended expansion of the study into the multi-dose phase (cohort 4) based on the initial data from cohort 3.

“We remain incredibly excited about our SAR-bisPSMA programs. It is remarkable to see these patients, who have failed so many lines of therapy in the past, now respond to treatment with ⁶⁷Cu-SAR-bisPSMA and with such a favorable safety profile. Based on these promising results, we have just opened the multi-dosing phase at the highest dose of 12GBq, and all slots for the first part of cohort 4 have now been allocated, aiming to have the first participant treated in this cohort within weeks,” said Clarity’s executive chairperson Alan Taylor, PhD, in the news release.¹

At the time of data report, no dose-limiting toxicities were observed among any patients treated in cohort 3 of the study. Among all patients dosed in the study so far (cohorts 1, 2, and 3, at the dose levels of 4, 8, and 12 GBq, respectively), the theranostic has demonstrated a favorable safety profile, with most adverse events (AEs) being mild or moderate.

Additionally, 67% of patients in cohort 3 demonstrated reductions in prostate-specific antigen (PSA) of greater than 35%. Among all patients treated in the study, 60% demonstrated a PSA reduction of greater than 35%, and 27% demonstrated a PSA reduction of greater than 80%.

With combined data from patients in cohorts 2 and 3 of the study, almost 80% of patients demonstrated PSA reductions of greater than 35% with a single dose of ⁶⁷Cu-SAR-bisPSMA, and 44% of patients showed PSA reductions of greater than 80%.

Overall, the phase 1/2a SECuRE trial is enrolling heavily pre-treated patients with advanced mCRPC. Cohort 3 of the trial included 6 patients who received single-dose administration of ⁶⁷Cu-SAR-bisPSMA at the highest dose level of 12 GBq.

Patients enrolled in cohort 3 of the study had the highest number of pre-treatments prior to entering the study, with most patients having received 5 or more prior lines of therapy. Those enrolled in cohort 3 also demonstrated the highest pre-treatment median PSA levels across all cohorts at 140.3 ng/mL.

In total, the study plans to enroll up to 44 patients across the US,² with enrollment for cohort 4 of the study now open. Participants enrolled in cohort 4 will receive multiple treatment cycles of ⁶⁷Cu-SAR-bisPSMA at the dose level of 12 GBq.

Additional data on ⁶⁴Cu/⁶⁷Cu-SAR-bisPSMA

Multiple treatment doses of ⁶⁷Cu-SAR-bisPSMA have already been explored in the SECuRE trial under the Expanded Access Program (EAP). The EAP enabled some patients who had shown clinical benefit during the dose escalation phase of the study to received additional cycles of ⁶⁷Cu-SAR-bisPSMA.

“Given the outstanding data in the trial so far, what is most important for us now is the longevity of response, and the results we have seen from 2 case studies conducted under the EAP are extremely encouraging,” said Taylor in the news release.¹ 

Data from the first patient treated with additional doses under the EAP showed a PSA reduction of 61.7% following a single dose of ⁶⁷Cu-SAR-bisPSMA at the dose level of 4 GBq. Following continued PSA decreases, 3 additional doses of ⁶⁷Cu-SAR-bisPSMA were requested. After receiving 4 total doses of ⁶⁷Cu-SAR-bisPSMA, the patient showed an overall PSA reduction of 93.7%, to 1 ng/mL, confirmed at 13 months following the first treatment dose.

Further, the patient demonstrated a decrease in the uptake of ⁶⁷Cu-SAR-bisPSMA, as measured by SPECT. No AEs related to either ⁶⁴Cu-SAR-bisPSMA or ⁶⁷Cu-SAR-bisPSMA were observed.

A second patient in the study also received additional doses of ⁶⁷Cu-SAR-bisPSMA under the EAP. The patient had received a single dose of ⁶⁷Cu-SAR-bisPSMA at the dose level of 8 GBq and demonstrated a PSA reduction of 99.4%. A second dose of ⁶⁷Cu-SAR-bisPSMA was requested, which led to a PSA reduction to undetectable levels. Additionally, PET was unable to detect any cancer and the patients demonstrated a near complete response at last follow-up. A complete response was not fully obtained due to the reduction in the size of 1 lymph node missing the complete response cutoff by 2 mm at the time of imaging. Mild to moderate AEs were reported, including dry mouth, altered taste, and fatigue, none of which required treatment. All AEs improved or resolved over time.

Taylor concluded, “We look forward to replicating the case study results in the multi-dose phase of the trial at the higher dose of 12GBq. If we observe a similar response in larger patient numbers, ⁶⁷Cu-SAR-bisPSMA may become the gold standard therapeutic agent for patients with mCRPC once approved.”¹

Reference

1. Clarity's theranostic prostate cancer trial advances to multi-dose phase. News release. Clarity Pharmaceuticals. March 15, 2024. Accessed March 18, 2024. https://www.claritypharmaceuticals.com/news/secure_c4/

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 October 12, 2023. https://clinicaltrials.gov/study/NCT04868604