Trial of 67Cu-SAR-bisPSMA in mCRPC progresses through multi-dose cohort

Treatment with multiple cycles of ⁶⁷Cu-SAR-bisPSMA showed encouraging safety and efficacy based on preliminary data from the first 3 patients enrolled in cohort 4 of the SECuRE trial (NCT04868604), which is assessing the theranostic in patients with metastatic castration-resistant prostate cancer (mCRPC), Clarity Pharmaceuticals announced in a news release.¹

Two patients who completed the DLT period achieved a greater than 60% decline in PSA levels.

Based on these data, the Safety Review Committee (SRC) has recommended that the trial proceed with dosing the final 3 patients in the cohort. Pending a positive safety evaluation of the final 3 patients, the dose expansion phase of the trial will commence with 14 participants.

“The early approval by the SRC to progress with the trial and the excellent safety data to date reinforce our confidence that ⁶⁷Cu-SAR-bisPSMA has a favorable safety profile as we consider the dosing schedule for the next phase of the trial,” said Alan Taylor, PhD, Clarity’s Executive chairperson, in the news release.¹ “The data from all cohorts is now presenting a unique proposition of a great safety profile coupled with remarkable efficacy, even in patients who had failed so many previous lines of therapy.”

Cohort 4 is the first cohort in the trial to assess multi-dose treatment of ⁶⁷Cu-SAR-bisPSMA at the highest dose level of 12 GBq. Among the first 3 patients enrolled in the cohort, 2 have completed the dose-limiting toxicity (DLT) period and 1 will complete the DLT period by the end of September. At the time of data report, no DLTs have been reported, which is in line with results from cohorts 1, 2, and 3.

Additionally, almost all adverse events (AEs) were either mild or moderate, with the majority having resolved or improved at the last assessment. In the patient who has not yet completed the DLT period, the only AE that has been reported so far is nausea, which has resolved.

Regarding efficacy, 2 patients who completed the DLT period achieved a greater than 60% decline in prostate-specific antigen (PSA) levels. The largest PSA decline was 92.3% in a patient who had previously failed multiple prior lines of therapy, and the PSA level is continuing to decline per the last assessment. The patient has already achieved a radiographic partial response per RECIST v1.1 with a 60.6% reduction in tumor volume on PSMA-PET imaging so far.

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 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.

Taylor concluded in the news release, “We are now using this data to inform the next stages of our clinical development program, including the expanded cohort in the SECuRE study and subsequently the Phase 3 clinical trial prior to regulatory approval and full commercial rollout. The positive safety profile of ⁶⁷Cu-SAR-bisPSMA, particularly compared to agents currently used to treat prostate cancer, lends itself to the treatment of patients much earlier in their disease, and we have commenced planning our clinical trials to focus on these earlier stages of prostate cancer.”¹

References

1. SECuRE trial advances: No dose limiting toxicities and strong preliminary efficacy data in first multi-dose cohort. News release. Clarity Pharmaceuticals. Published online and accessed September 12, 2024. https://www.claritypharmaceuticals.com/news/c4_update/

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 September 12, 2024. https://clinicaltrials.gov/study/NCT04868604