The SECuRE trial investigating ⁶⁷Cu-SAR-bisPSMA as a novel radiopharmaceutical therapy for metastatic castration-resistant prostate cancer (mCRPC) has reported significant advancements. The latest update highlights a 92% response rate among pre-chemotherapy participants after one single dose, showing a greater than 35% reduction in prostate-specific antigen (PSA) levels. The promising results have led to the trial’s progression into the Cohort Expansion Phase (Phase II), with an optimized treatment strategy aimed at further validating efficacy and safety.

One of the most notable findings came from Cohort 4, which assessed multiple administrations of  ⁶⁷Cu-SAR-bisPSMA. In this group, three participants experienced PSA reductions of 80% or more, with one achieving a complete response after just two doses of 12 GBq. Across all study cohorts, 68% of participants saw declines in PSA levels, despite 77% of them receiving only a single dose.

While the majority of participants responded positively, non-responders were often those who had previously undergone chemotherapy in the mCRPC setting, were part of the lowest dose cohort, or had exceptionally high PSA levels at the beginning of the study. These findings suggest that earlier intervention with 67Cu-SAR-bisPSMA, before chemotherapy, could lead to better outcomes.

The treatment has demonstrated a favorable safety profile across all study cohorts. Most adverse events (AEs) were mild to moderate (Grade 1-2), with anemia and thrombocytopenia being the most common hematological effects. Nearly all reported AEs have resolved, reinforcing the drug’s tolerability.

Among the 13 participants who had not received chemotherapy in the mCRPC setting (taxane-naïve in the metastatic castration-resistant prostate cancer stage), 12 exhibited PSA reductions of at least 35%, and nearly half experienced declines of 80% or more. Disease control, as assessed by the RECIST criteria, was achieved in 92% of these pre-chemotherapy participants.

Some participants who had previously received actinium-225-based radioligand therapies also demonstrated significant PSA reductions after treatment with 67Cu-SAR-bisPSMA. One such patient, after receiving two doses of 12 GBq, showed an 83.4% decrease in PSA levels, despite heavy prior treatment with multiple therapies, including androgen receptor pathway inhibitors and investigational agents.

Encouraged by these promising findings, the trial is moving into the Cohort Expansion Phase (Phase II). The number of participants will increase from 14 to 24, allowing for broader validation of the treatment’s effectiveness. A subset of participants will also receive a combination of ⁶⁷Cu-SAR-bisPSMA with enzalutamide, a widely used androgen receptor pathway inhibitor, to evaluate potential synergistic effects.

The Cohort Expansion Phase will primarily focus on pre-chemotherapy participants, reflecting the strategy to introduce ⁶⁷Cu-SAR-bisPSMA in earlier treatment settings. Data so far suggest that the therapy has the potential to improve outcomes significantly in patients who have not yet undergone chemotherapy in the mCRPC stage.

With these highly encouraging results, the SECuRE trial is well-positioned for a potential Phase III pivotal trial in the near future. The data collected in the Cohort Expansion Phase will be crucial in shaping the final design and regulatory pathway for broader approval. If results continue to show strong efficacy and safety, ^67Cu-SAR-bisPSMA could become a game-changer in the treatment of metastatic castration-resistant prostate cancer.

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