On March 15, 2024 Clarity Pharmaceuticals, a clinical stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported the successful completion of cohort 3 and advancement to cohort 4, the first multi-dose cohort in the SECuRE trial (Press release, Clarity Pharmaceuticals, MAR 15, 2024, View Source [SID1234641160]).

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The SECuRE trial (NCT04868604)1 is a Phase I/IIa theranostic trial for identification and treatment of Prostate-Specific Membrane Antigen (PSMA) expressing 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 trial with a cohort expansion involving up to 44 patients in the US. The aim of the trial is to determine the safety and efficacy of 67Cu-SAR-bisPSMA for the treatment of prostate cancer.

Cohort 3 of the dose escalation phase of the trial, where 6 participants received a single administration of 12GBq of 67Cu-SAR-bisPSMA, has been successfully completed. No DLTs have been reported in any of the participants dosed in this cohort to date. The SRC, responsible for assessing safety of participants and overseeing the general progress of the trial, has assessed the data and recommended progressing the trial to cohort 4 where participants will be treated with multiple therapy cycles of 67Cu-SAR-bisPSMA at a dose level of 12GBq, the highest dose level in the dose escalation phase of the trial.

Anti-tumour effect of 67Cu-SAR-bisPSMA

All participants in the SECuRE trial had advanced prostate cancer (stage IV, mCRPC). Assessment of the baseline characteristics of these patients showed that they were heavily pre-treated before entering the study, having received multiple therapies for their disease. Those treatments included ADT, ARPI, several investigational agents (targeting different pathways of the cancer), chemotherapy and other radioligand therapies. Most trial participants had received chemotherapy (67%, 10/15) and the median number of lines of therapy prior to receiving 67Cu-SAR-bisPSMA was 4. The median PSA at study entry was 117.1 ng/ml (range 0.11-1,494.2).

Preliminary data shows that despite having high levels of PSA and having received multiple treatments, 60% (9/15) of participants across all cohorts (including the lowest dose cohort of 67Cu-SAR-bisPSMA at 4GBq) showed reductions in PSA levels of greater than 35% from a single therapy cycle of 67Cu-SAR-bisPSMA. PSA reductions of greater than 80% were seen in 27% of all trial participants. In cohorts 2 and 3 (8 and 12GBq, respectively), PSA reductions of greater than 35% were observed in almost 80% (78%, 7/9) of participants and PSA was reduced by greater than 80% in 44% (4/9) of participants so far.

Participants in cohort 3 had the highest median baseline PSA and the highest median number of systemic therapies across all cohorts (median baseline PSA 122.6, 47.2 and 140.3 ng/ml; median lines of therapy 4, 3 and 5.5; cohorts 1, 2 and 3, respectively). Nevertheless, two-thirds (67%) of participants in this cohort so far have shown reductions in PSA greater than 35%, with the last participants in this cohort dosed in January 2024. Importantly, a single dose of 12GBq of 67Cu-SAR-bisPSMA was effective in reducing PSA levels in the majority of these patients despite receiving the most lines of prior therapy