The SECURE trial exploring 64Cu/67Cu SAR-bisPSMA in patients with metastatic castration-resistant prostate cancer has advanced to the highest dose level.
The novel treatment 64Cu/67Cu SAR-bisPSMA continued to demonstrate positive efficacy and safety outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC), as the phase 1/2 SECURE trial has now advanced to the highest dose level of the theranostic.1
Clarity Pharmaceuticals, the developer of 64Cu/67Cu SAR-bisPSMA, reported in a press release that cohort 2 of the trial, in which patients were dosed at 8 GBq, has been successfully completed and based on the recommendation of the Safety Review Committee, the study has advanced to cohort 3. Patients enrolled in cohort 3, which is already recruiting, will receive the highest study dose level of 12 GBq.1
The theranostic 64Cu/67Cu SAR-bisPSMA combines the PSMA-PET imaging agent 64Cu-SAR-bisPSMA and the PSMA targeted therapy 67Cu-SAR-bisPSMA. In the SECURE trial, 64Cu-SAR-bisPSMA is being used for the selection of appropriate patients to receive treatment with 67Cu-SAR-bisPSMA.2
According to Clarity, cohort 2 comprised 3 patients treated with a single dose of 67Cu SAR-bisPSMA at 8 GBq. There have been no dose-limiting toxicities reported with this dose and all 3 patients remain on the trial. All 3 of the patients have experienced a reduction in their PSA level, and 2 of the patients had an initial PSA reduction of approximately 90%.1
Cohort 3 will be the final cohort assessing single doses of 67Cu SAR-bisPSMA. The ensuing cohort is scheduled to be a multi-dose cohort.
"We are excited by the remarkable PSA declines seen in all three patients in cohort 2 with just a single dose of 8 GBq of 67Cu SAR-bisPSMA. I have not observed PSA responses like this after a single dose of any agent and, considering the excellent safety profile we have seen to date in the first two cohorts of this study, we really look forward to progressing the development of this promising therapy. While in the VISION trial with 177Lu PSMA-617 we did see a >80% reduction in PSA in roughly 33% of patients, this was after up to six 7.4 GBq doses of 177Lu PSMA-617 spaced out over a period of up to 30 weeks. If a single 8 GBq dose of 67Cu SAR-bisPSMA can deliver so much benefit to the patients, we are excited to see how a single 12 GBq dose will benefit patients in cohort 3 and to explore the effect of multiple dosing. If similar responses can be replicated in larger patient numbers, 67Cu SAR-bisPSMA may become the gold standard therapeutic agent for patients with mCRPC once approved," Luke Nordquist, MD, CEO, urologic medical oncologist and principal investigator at the Urology Cancer Center/XCancer Omaha, Nebraska, stated in a press release.1
To enroll in the open-label, single-arm, dose-escalation SECURE trial, patients must have mCRPC that has progressed despite being treated with androgen-deprivation therapy and at least 1 second-generation androgen receptor pathway inhibitor, such as abiraterone acetate (Zytiga) or enzalutamide (Xtandi).2 Patients are required to have an ECOG performance status of 0 to 2, and a castrate level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L). Individuals with brain metastases are not eligible to enroll.
Clarity previously reported that cohort 1 of the SECURE trial was completed. Cohort 1 included 6 patients with mCRPC who all received 67Cu SAR-bisPSMA at the lowest dose level of 4 GBq. The study investigators reported that there were no dose-limiting toxicities at this dose level.3
Of note, clinicians have requested additional treatment cycles of 67Cu SAR-bisPSMA under the FDA Expanded Access Program for patients who were part of the SECURE trial.1
1. Clarity's theranostic prostate cancer trial advances to highest dose level. Accessed August 11, 2022. https://www.prnewswire.com/news-releases/claritys-theranostic-prostate-cancer-trial-advances-to-highest-dose-level-301897641.html
2. NIH ClinicalTrials.gov. 64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for Identification and Treatment of PSMA-expressing Metastatic Castrate Resistant Prostate Cancer (SECURE). Last updated May 24, 2023. Accessed August 10 , 2023. https://clinicaltrials.gov/ct2/show/NCT04868604
3. Clarity's theranostic prostate cancer trial advances to cohort 2. Accessed May 24, 2023. https://www.prnewswire.com/news-releases/claritys-theranostic-prostate-cancer-trial-advances-to-cohort-2-301833001.html