Clarity Pharmaceuticals (ASX: CU6) has successfully completed cohort 2 and advanced to cohort 3 in the dose escalation phase of its Phase I/II theranostic trial, SECuRE, evaluating 64Cu/67Cu SAR-bisPSMA in patients with mCRPC.
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.
The second cohort of the dose escalation, where three participants received a single administration of 8GBq of 67Cu SAR- bisPSMA, has been completed. No DLTs have been reported in any of the patients dosed 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 3, increasing the dose to 12GBq.
The third cohort will be the last to assess single doses of 67Cu SAR-bisPSMA and will be followed by a multi-dose cohort, pending safety evaluation. The 3 participants in cohort 2 have been monitored by their physicians for safety and treatment response as per the trial protocol. All three participants in cohort 2 remain on the trial following their recent administration of 8GBq of 67Cu SAR- bisPSMA and are demonstrating a PSA reduction, with 2 of the 3 participants exhibiting an initial PSA reduction of ~90%. A PSA decline 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.
We are excited by the remarkable PSA declines seen in all three patients in cohort 2 with just a single dose of 8GBq of 67Cu SAR-bisPSMA,” Dr Luke Nordquist, CEO, Urologic Medical Oncologist and Principal Investigator at the Urology Cancer Center / XCancer Omaha, NE, said.
“I have not observed PSA responses like this after a single dose of any agent and, considering the excellent safety profile we have seen to date in the first two cohorts of this study, we really look forward to progressing the development of this promising therapy.
“While in the VISION trial2 with 177Lu PSMA-617 we did see a >80% reduction in PSA in roughly 33% of patients, this was after up to six 7.4GBq doses of 177Lu PSMA- 617 spaced out over a period of up to 30 weeks. If a single 8GBq dose of 67Cu SAR-bisPSMA can deliver so much benefit to the patients, we are excited to see how a single 12GBq dose will benefit patients in cohort 3 and to explore the effect of multiple dosing.
“If similar responses can be replicated in larger patient numbers, 67Cu SAR-bisPSMA may become the gold standard therapeutic agent for patients with mCRPC once approved.”
Additional therapy cycles of 67Cu SAR-bisPSMA have been requested by clinicians under the FDA EAP for patients who participated in the SECuRE trial.
“SPECT-CT images depicted below were collected 48 hours after the first, third and fourth administrations of 4GBq of 67Cu SAR-bisPSMA in a patient from cohort 1 who received additional cycles under the EAP.
“SPECT-CT images collected following the third and fourth therapy cycle demonstrate a reduction in the intensity of therapeutic 67Cu SAR-bisPSMA product uptake at the tumour sites. A reduction of greater than 50% in PSA levels was observed in this patient following the first administration of 4GBq of therapeutic 67Cu-SAR-bisPSMA and a drop of greater than 90% in PSA was observed after the fourth administration of 4GBq of 67Cu-SAR-bisPSMA.”