SECuRE Trial Highlights Safety, Efficacy of 67Cu-SAR-bisPSMA in mCRPC
The dose-escalation phase of the SECuRE trial in prostate cancer has completed and demonstrated promising safety and efficacy data.
3D rendering of prostate cancer
The phase 1/2a SECuRE trial (NCT04868604) evaluating the safety and efficacy of 67Cu-SAR-bisPSMA for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) has completed its dose-escalation phase and demonstrated encouraging results.1
The SECuRE trial, which enrolled heavily pretreated patients with advanced mCRPC, including those with extensive bone metastases and high baseline prostate-specific antigen (PSA) levels, showed that 68% of patients across cohorts 1 to 4 experienced reductions in PSA levels, with 78% achieving disease control, based on radiographic assessment. Two partial responses (PR) and 1 complete response (CR) were observed, with the CR occurring in a patient who received 2 doses of 12 GBq. This marks the second CR reported in the trial, following a prior CR in a patient treated with 2 doses of 8 GBq.
In the pre-chemotherapy subset of 13 patients, 92% (12/13) achieved PSA reductions greater than 35%, with 61.5% (8/13) experiencing reductions greater than 50%, and 46.2% (6/13) achieving reductions of 80% or more. Disease control was observed in 92% of pre-chemotherapy patients with measurable disease at baseline, including 1 CR, 2 PRs, and 8 cases of stable disease (SD).
“The SECuRE trial continues to generate extraordinary results, and we thank our team, principal investigators, members of the [safety review committee], and especially the participants who have contributed to the study. Seeing the safety profile and already observing impressive signs of efficacy (despite the majority of participants only receiving a single cycle of 67Cu-SAR-bisPSMA and the primary focus of the dose escalation phase being safety assessments), we are thrilled to progress to phase 2, the cohort expansion phase, of our theranostic SECuRE trial,” explained Alan Taylor, MD, executive chairperson at Clarity Pharmaceuticals, in a press release.
The safety profile of 67Cu-SAR-bisPSMA was favorable, with the majority of adverse events (AEs) being grade 1 or 2. Hematological toxicities like anemia and thrombocytopenia were the most common AEs, and there were no significant trends in renal toxicity or other hematological parameters observed.
There was 1 dose-limiting toxicity reported—a transient grade 4 thrombocytopenia in a heavily pretreated patient with extensive bone metastases and a baseline PSA of 1503.12 ng/mL. However, a single dose of 67Cu-SAR-bisPSMA reduced this patient's PSA by 10.7%. In the pre-chemotherapy subset of patients, the safety profile was consistent with the overall population, with most AEs being mild to moderate.
The trial has now progressed to the phase 2, cohort expansion phase, based on the recommendation of the safety review committee. The optimal dose of 8 GBq has been identified for further evaluation and experts are recommended to increase the number of cycles from up to 4 to up to 6.
Additionally, the trial protocol has been amended to include more pre-chemotherapy patients and explore combination therapy with the androgen receptor pathway inhibitor (ARPI) enzalutamide (Xtandi).
"We look forward to swiftly recruiting into the next phase of the SECuRE trial, moving towards a phase 3 pivotal trial. We are very excited about what the future holds for this promising product and are working tirelessly to bring it to people who need it most in a timely manner, whilst adhering to the highest standards of clinical research," Taylor added in the press release.
About the SECuRE Trial
SECuRE is a phase 1/2a theranostic study evaluating patients with prostate-specific membrane antigen (PSMA)-expressing mCRPC using 67Cu SAR-bisPSMA. Enrollment in the study is open to patients aged 18 years and older with histological, pathological, and/or cytological confirmation of prostate cancer who have a life expectancy >6 months, an ECOG performance status of 0, 1, or 2, a positive 64Cu-SAR-bisPSMA PET/CT scan, castrate level of serum/plasma testosterone, and adequate organ function.2
Patients must also have progressive mCRPC, despite prior androgen deprivation therapy, and at least enzalutamide and/or abiraterone acetate (Zytiga), have ≥1 metastatic lesion present at screening CT, MRI, or bone scan imaging ≤28 days before study enrollment, and have recovered to ≤ grade 2 from all clinically significant toxicities related to prior therapies.
In February 2025, the FDA granted fast track designation to 67Cu-SAR-bisPSMA for treating adult patients with PSMA-positive mCRPC who have been previously treated with an ARPI.3
This designation was based on promising preliminary data from the ongoing phase 1/2a SECuRE trial. Early results showed significant PSA reductions across various dose levels. Notably, 73% of evaluable patients across all dose-escalation cohorts experienced a decrease in PSA levels, with 45% achieving reductions greater than 50%, even with a single dose of 67Cu-SAR-bisPSMA at either 4, 8, or 12 GBq.
Further analysis of patients in cohorts 2, 3, and 4, who received single 8-GBq, single 12-GBq, and 12-GBq multidose regimens, respectively, showed that nearly 75% of patients had PSA reductions exceeding 35%, and almost half achieved reductions of at least 80%.
The initial dose-escalation phase (n = 15) also demonstrated a favorable safety profile. No dose-limiting toxicities were observed, and treatment-related AEs were primarily grade 1 or 2, with the most common being grade 1 dry mouth (33.3%).
REFERENCES:
SECuRE trial update: 92% of pre-chemo participants experience greater than 35% drop in PSA levels across all cohorts. Cohort expansion phase commences. News release. Clarity Pharmaceuticals. March 5, 2025. Accessed March 5, 2025. https://tinyurl.com/2fruvv9c
64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for identification and treatment of PSMA-expressing metastatic castrate resistant prostate cancer (SECuRE). ClinicalTrials.gov. Updated March 27, 2024. Accessed March 5, 2025. https://clinicaltrials.gov/study/NCT04868604
Clarity receives US FDA fast track designation for the treatment of metastatic castration-resistant prostate cancer patients with Cu-67 SAR-bisPSMA. News release. Clarity Pharmaceuticals. February 19, 2025. Accessed March 5, 2025. https://tinyurl.com/36v768eb
