Clarity Pharmaceuticals has initiated patient enrollment for the COBRA trial, a phase 1/2 study investigating 64Cu SAR-bisPSMA as a novel PSMA-PET imaging agent for detecting biochemically recurrent prostate cancer. The multicenter, nonrandomized, single-arm trial (NCT05249127) targets enrollment of 50 patients with suspected prostate cancer recurrence following definitive therapy.
Trial Design and Patient Population
The COBRA trial will enroll patients with biochemical recurrence (BCR) of prostate cancer as determined by rising prostate-specific antigen (PSA) levels. For patients who underwent radical prostatectomy, eligibility requires detectable or rising PSA ≥ 0.2 ng/mL with confirmatory PSA ≥ 0.2 ng/mL. Patients who received radiation, cryotherapy, or brachytherapy must demonstrate PSA elevation ≥2 ng/mL above nadir according to the ASTRO Phoenix definition of biochemical failure.
The study's primary endpoints focus on evaluating 64Cu SAR-bisPSMA's ability to detect prostate cancer recurrence while assessing safety and tolerability. The estimated primary completion date is April 2023.
Clinical Significance and Advantages
"We are very excited to initiate patient accrual for the COBRA trial which will explore and validate the clinical benefits associated with the novel SAR-bisPSMA agent," stated Neal Shore MD, FACS, lead principal investigator and CMO of Urology/Surgical Oncology at GenesisCare US. Shore highlighted that preliminary data from Clarity's SECURE and PROPELLER trials, along with preclinical studies, demonstrate high uptake of Copper-64 SAR-bisPSMA, suggesting improved prostate cancer detection capabilities.
The imaging agent shows particular promise for detecting very low volume disease, which is especially critical for patients with suspected disease recurrence. Shore emphasized the logistical advantages of central manufacture and on-demand delivery, which will enhance accessibility to treatment facilities across the United States.
Expanding Clinical Development Program
Beyond COBRA, Clarity Pharmaceuticals is advancing multiple trials exploring 64Cu SAR-bisPSMA applications. The X-Calibur trial (NCT05286840) represents a prospective, nonrandomized, single-arm, single-center, open-label phase 1/2 study recruiting 150 patients with known or suspected prostate cancer. This study prioritizes safety as its primary outcome measure, with secondary endpoints including disease status adjustment, disease staging adjustment, and clinical management plan modifications following 64Cu SAR-bisPSMA PET/CT imaging.
The SECURE trial (NCT04868604) takes a theranostic approach, examining both 64Cu SAR-bisPSMA for imaging and 67Cu SAR-bisPSMA for targeted therapy in patients with metastatic castration-resistant prostate cancer. This open-label, single-arm, dose-escalation study aims to enroll 44 patients across multiple US locations, using 64Cu SAR-bisPSMA to select appropriate candidates for 67Cu SAR-bis-PSMA treatment.
Technical Specifications and Implementation
The X-Calibur trial protocol requires patients to receive a single administration of 64Cu SAR-bisPSMA followed by PET scans at early (1-4 hours) and late (24-72 hours) time points. Eligible participants include males over 18 years with confirmed prostate adenocarcinoma or suspected prostate cancer based on elevated PSA with negative standard imaging and/or biopsy results.
The study excludes patients who received investigational agents within 28 days or high-energy gamma-emitting radioisotopes within 5 physical half-lives prior to 64Cu SAR-bisPSMA administration. Participants must maintain adequate renal function with eGFR ≥30 ml/min/1.73m² and ECOG performance status 0-2.
