On September 12, 2024 Clarity Pharmaceuticals (ASX: CU6) ("Clarity", "the Company"), a clinical stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported an update on the safety review of the first 3 participants enrolled in cohort 4 of the SECuRE trial who received 2 doses of 67Cu-SAR-bisPSMA (Press release, Clarity Pharmaceuticals, SEP 12, 2024, View Source [SID1234646526]). Cohort 4 is the final cohort in the dose escalation phase of the study, with participants receiving a minimum of 2 and a maximum of 4 doses of 67Cu-SAR-bisPSMA at 12GBq.
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The SECuRE trial (NCT04868604)1 is a Phase I/IIa theranostic trial for identification and treatment of participants with prostate-specific membrane antigen (PSMA)-expressing metastatic castrate-resistant prostate cancer (mCRPC) using 64Cu/67Cu-SAR-bisPSMA. 64Cu-SAR-bisPSMA is used to visualise PSMA-expressing lesions and select candidates for subsequent 67Cu-SAR-bisPSMA therapy. The trial is a multi-centre, single arm, dose escalation study with a cohort expansion involving approximately 44 participants in the US and Australia. The overall aim of the trial is to determine the safety and efficacy of 67Cu-SAR-bisPSMA for the treatment of prostate cancer.
Cohort 4 is the first to explore the safety and anti-cancer effects of multiple therapy cycles of 67Cu-SAR-bisPSMA at the highest dose of 12GBq. This is the last cohort of the dose escalation phase, before the trial advances into its Phase II stage (cohort expansion) in 14 participants, pending safety evaluation.
Cohort 4 is designed as a "3+3" cohort, where participants will receive a minimum of 2 therapy cycles. Based on the positive safety profile observed in the first 3 cohorts of the SECuRE trial, a change to the dosing schedule of cohort 4 from "2 doses" to "up to 4 doses" has previously been approved by the SRC. This will allow participants who are benefiting from 67Cu-SAR-bisPSMA to receive 2 additional doses under the SECuRE trial (up to 4 doses in total) (Figure 1).
Safety & Efficacy
The SRC has reviewed the safety data of the first 3 participants of cohort 4 who have received 2 cycles of 67Cu-SAR-bisPSMA, and no DLTs have been observed to date. Two participants have completed the DLT period, and 1 participant will complete the DLT period by the end of September. Almost all AEs were mild to moderate, with the majority having resolved or improved at the last assessment. In the final participant who is yet to complete the DLT period, the only AE reported to date was nausea, which has resolved.
Early preliminary efficacy assessment shows a reduction in PSA levels following treatment in both participants who have completed the DLT period. In the weeks following the last therapy dose, these participants have already exhibited PSA drops of more than 60%. The largest drop in PSA to date was a fall of 92.3% (from a baseline PSA of 157.4 ng/mL), and it continues to decline based on the latest assessment. This participant, who had failed several lines of therapy prior to receiving 67Cu-SAR-bisPSMA (i.e. androgen deprivation therapy [ADT], androgen receptor pathway inhibitor [ARPI] and an investigational agent through a clinical trial), has already had a radiographic partial response based on Response Evaluation Criteria in Solid Tumours v1.1 (RECIST) assessment, with a reduction of 60.6% in tumour volume evaluated by PSMA positron emission tomography (PET) imaging thus far (Figure 2).