Clarity Pharmaceuticals announced that the first patient ever to be dosed with two cycles of 8GBq of 67Cu-SAR-bisPSMA has had a drop in PSA to undetectable levels, undetectable disease using PET and a near complete response to treatment under RECIST. The patient received the first cycle as part of cohort 2 of Clarity's theranostic trial, SECuRE, evaluating 64Cu/67Cu-SAR-bisPSMA in patients with mCRPC, and a second cycle under the US FDA EAP, as requested by the patient's clinician. The patient experienced a mild dry mouth, altered taste and moderate fatigue, all adverse events resolved themselves.

Following the administration of two cycles of 67Cu-SAR-bisPSMA at the 8GBq dose level, the near complete response (absence of all detectable cancer after treatment) was reported following the Response Evaluation Criteria In Solid Tumours (RECIST) assessment. The patient had already failed multiple lines of treatment, including hormone therapy, an investigational agent and chemotherapy prior to being treated with 67Cu-SAR-bisPSMA. The patient had a reduction in PSA levels from 47.2 ng/L at baseline to an undetectable level of less than 0.05 ng/ml ?

Figure 3. PSA is a well characterised marker of tumour burden, clinical response to treatment and an indicator of the recurrence of disease for prostate cancer. Moreover, PSA decline is an independent prognostic indicator of improved overall survival following radioligand therapy. As previously reported, one third of participants (2/6) in the SECuRE trial cohort 1, the lowest dose cohort of 4GBq, had a PSA decline greater than 50% from a single cycle of 67Cu-SAR-bisPSMA.

In cohort 2, all participants (3/3) had a PSA decline greater than 80% from a single 8GBq cycle, with two showing greater than 95% drops in PSA. In cohort 3, two thirds of participants (2/3) showed reductions in PSA levels of approximately 40% and over 90% each. One of the patients in cohort 3 will be soon receiving his second dose of 67Cu-SAR-bisPSMA at 12GBq under EAP.

A PSA drop of 50% or greater is one of the primary endpoints of the SECuRE trial and a commonly used surrogate endpoint for efficacy in this patient population. Importantly, no DLTs have been reported in the SECuRE trial in any of the patients dosed with 67Cu-SAR-bisPSMA to date. Recruitment is ongoing into cohort 3 of the trial where the dose level has been increased to the highest single dose level of 12GBq.