Study of novel PSMA theranostic shows positive initial safety and efficacy

Treatment with the novel theranostic ⁶⁴Cu/⁶⁷Cu SAR-bisPSMA yielded positive safety and efficacy signals in patients with metastatic castration-resistant prostate cancer (mCRPC), according to early data from the phase 1/2a SECURE trial (NCT04868604).¹

“Outside of reductions in PSA levels and changes in tumor imaging, we have seen an improvement in quality-of-life measures such as reduction in pain and return of appetite and physical exercise. It is fantastic to see benefits at the lowest dose level, and we look forward to progressing to cohort 2 and increasing the dose of 67Cu SAR-bisPSMA," said Luke Nordquist, MD.

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.

In a press release, Clarity Pharmaceuticals, the developer of the theranostic, reported that the initial cohort from the SECURE trial (cohort 1) has been 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.

Based on these safety findings, the study’s Safety Review Committee recommended that the trial proceed to cohort 2, in which the dose level ⁶⁷Cu SAR-bisPSMA will be increased to 8 GBq. Patient screening is currently ongoing for enrollment in this cohort.

Outside of the trial, early data from the FDA Expanded Access Program (EAP) have shown positive signals of clinical activity with ⁶⁷Cu SAR-bisPSMA. Specifically, SPECT-CT images showed that the 4 GBq dose used in cohort 1 led to a reduction in PSA levels. In one patient, a >50% reduction in PSA level was observed. Further, clinicians have requested additional treatment cycles of ⁶⁷Cu SAR-bisPSMA under the EAP for patients who participated in cohort 1.

“We are excited to have successfully completed the first cohort of the SECURE trial. We have not seen any safety issues in the patients treated so far and are already seeing clinical benefits in some patients,” Luke Nordquist, MD, CEO, urologic medical oncologist and principal investigator at the Urology Cancer Center/XCancer, stated in the press release. “Outside of reductions in PSA levels and changes in tumor imaging, we have seen an improvement in quality-of-life measures such as reduction in pain and return of appetite and physical exercise. It is fantastic to see benefits at the lowest dose level, and we look forward to progressing to cohort 2 and increasing the dose of ⁶⁷Cu SAR-bisPSMA."

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.

Across all phases of the study, the total enrollment goal is 44 patients. The study is being conducted at 7 locations in the United States.

"For this product, we went back to the drawing board. We saw the limitations of first-generation PSMA agents, with single PSMA targeting molecules, including low uptake in tumors and poor retention over time. Utilizing two PSMA targeting molecules in our optimized agent, bisPSMA, and the TCT platform, we have observed two to three times the uptake of product in tumors so far in pre-clinical and clinical development and saw retention in the tumors out to 96 hours. We are excited by the results of this innovation seen to date as we work towards developing best-in-class products across both diagnostic and therapeutic applications” Dr Alan Taylor, executive chairman of Clarity, stated in the news release.

References

1. 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

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 update May 3, 2021. Accessed May 5, 2021. https://clinicaltrials.gov/ct2/show/NCT04868604.