- The disease
- Metastatic castrate-resistant prostate cancer (mCRPC) is prostate cancer that has spread beyond the prostate and continues to grow despite surgical or medical reduction of testosterone to low levels. It is considered an advanced stage of the disease and is associated with significant morbidity. A protein called prostate-specific membrane antigen (PSMA) is expressed at high levels on the surface of most prostate cancer cells, making it a target for both imaging and treatment.
- What the asset is trying to do
- SAR-bisPSMA is a copper-based theranostic agent, meaning the same molecule can be used for both imaging and therapy by swapping the copper isotope. The diagnostic version uses copper-64 (64Cu), a positron-emitting isotope that enables positron emission tomography (PET) scans to locate PSMA-expressing cancer cells throughout the body (per ClinicalTrials.gov NCT04868604). The therapy version uses copper-67 (67Cu), which emits beta and Auger electrons that can damage and kill nearby cancer cells (per ClinicalTrials.gov NCT04868604). This paired imaging-and-treatment approach differs from some approved PSMA radioligand therapies that use separate agents for detection and treatment.
- What the trial is measuring, and why it matters
- The lead therapeutic trial (NCT04868604) is evaluating both the 64Cu imaging and 67Cu therapy forms across dose cohorts in men with PSMA-expressing mCRPC (per ClinicalTrials.gov NCT04868604). The study is designed as a Phase 1/2 trial, meaning early cohorts focus on safety and dosing while later cohorts assess preliminary evidence of tumour response (per ClinicalTrials.gov NCT04868604). Endpoints in radioligand therapy trials typically include safety measures such as dose-limiting toxicities as well as tumour response metrics, though the specific primary and secondary endpoints for this trial are noted below in the design section.
- Efficacy benchmarks in this setting
- In the approved PSMA-targeted radioligand therapy lutetium-177 PSMA-617 (177Lu-PSMA-617, brand name Pluvicto), the VISION Phase 3 trial in patients with PSMA-positive mCRPC who had previously received androgen receptor pathway inhibitors and taxane chemotherapy reported a radiographic progression-free survival of 8.7 months versus 3.4 months for the control arm, and an overall survival of 15.3 months versus 11.3 months (per Sartor et al, New England Journal of Medicine 2021, doi:10.1056/NEJMoa2107322). Cabozantinib, enzalutamide, abiraterone, and docetaxel each have established response and survival benchmarks in various mCRPC settings from their respective Phase 3 registration trials. SAR-bisPSMA's Phase 1/2 trial (NCT04868604) is at an early stage with a target enrolment of 54 participants, and any preliminary figures from that trial are not statistically comparable to the large, randomised, controlled trials underlying approved therapy benchmarks.