Phase 2 Trial of Cu-64 SAR-bisPSMA Doubles Prostate Lesion Detection

64Cu-SAR-bisPSMA represents a next-generation PSMA-targeted PET imaging agent for prostate cancer, demonstrating superior lesion and patient detection in the Phase 2 Co-PSMA trial announced in February 2026. In this head-to-head study of 50 patients with biochemical recurrence (BCR) after prostatectomy (PSA 0.2-0.75 ng/mL), Cu-64 SAR-bisPSMA more than doubled mean lesions per patient at 1.26 (63 total) compared to 0.48 (24 total) for standard-of-care 68Ga-PSMA-11, with a statistically significant ratio of 2.63 (P < .0001).
Positive scan rates reached 78% (39/50 patients) versus 36% (18/50), including 75% true positive rate versus 39% confirmed by histopathology in a subset. The trial leveraged Cu-64’s 12.7-hour half-life for next-day imaging on the same scanner, yielding higher tumor contrast and 44% management changes (e.g., from observation to therapy). These results build on prior COBRA data and position Cu-64 SAR-bisPSMA as a potential shift from 68Ga standards, especially in low-PSA BCR where early detection guides salvage therapy; topline supports ongoing Phase 3 CLARIFY trial.

To some, the idea of a tracer detecting more lesions than expected might be unsettling. Yet detecting more lesions also means the ligand is highly precise and effective, even when used for treatment. This may partly explain the success of the 67Cu-bisPSMA-based SECuRE trial.

Compared to F-18 PSMA tracers like piflufolastat (Pylarify), Cu-64 SAR-bisPSMA shows promise in surpassing detection metrics seen in meta-analyses where F-18 rivals or slightly edges 68Ga (50-70% BCR positivity vs 40-60%), but no direct head-to-head exists yet. F-18’s 110-minute half-life offers better logistics than 68Ga’s 68 minutes yet falls short of Cu-64’s extended window for optimized delayed imaging, which enhances low-PSA sensitivity without hepatobiliary artifacts plaguing some F-18 agents like PSMA-1007. Cu-64 detected over 2x lesions versus SOC (including F-18 benchmarks in substudies), with superior true positives, though F-18 maintains advantages in cyclotron production scalability.

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