UPDATE: SECuRE Trial Phase 2 Shows 67% PSA50 Response in Heavily Pre-Treated mCRPC

The latest interim update from the SECuRE trial reinforces the impression that copper‑67 PSMA targeting is emerging as a credible contender in the mCRPC radioligand space, with consistent PSA responses and a clean safety profile in a small but challenging population. The Safety Review Committee has endorsed continuation of the Phase 2 cohort expansion without any protocol changes, an important signal that dosing and toxicity are considered acceptable as the program moves toward registrational planning.

In this interim analysis, nine participants from the Phase2 cohort expansion had evaluable data by the 25 November 2025 cutoff, most of them representative of a late‑line mCRPC setting: 55.6% had received more than five prior systemic anticancer regimens and 66.7% had bone metastases at enrolment. Median baseline PSA was 18.9 ng/mL (range 1.5–30.2 ng/mL), and six of the nine participants had already received at least two cycles of 8 GBq of 67Cu‑SAR‑bisPSMA, with two of those six also treated with concomitant enzalutamide. Seven participants overall received monotherapy and two entered the 67Cu‑SAR‑bisPSMA plus enzalutamide combination arm.

The safety profile in this heavily pre‑treated group remains favourable. Across the nine participants, most treatment‑related adverse events were Grade 1–2, with nausea and lymphopenia each occurring in 33.3% of patients. Grade ≥3 lymphopenia was observed in three men, several of whom had baseline bone metastases and extensive prior therapy including taxanes and investigational agents, making causality less straightforward; importantly, no new renal toxicity signals or ECG changes have been seen to date. In the combination cohort with enzalutamide, no additional or worsened toxicities attributable to the radionuclide were reported, which is reassuring given the increasing interest in pairing PSMA radioligands with AR pathway inhibitors.

Among the nine Phase 2 participants, six had at least two post‑treatment PSA measurements available; all six experienced a PSA decline, with 66.7% (4/6) achieving PSA50 and 33.3% (2/6) reaching PSA80 thresholds. These response rates echo the prior dose‑escalation experience at the same dose, where 92% of pre‑chemotherapy participants had PSA drops greater than 35%, 61.5% achieved ≥50% reductions, and 46.2% reached ≥80% declines, all within a manageable safety framework. The decision to standardise on 8 GBq for up to six cycles in the expansion cohort is thus grounded in both tolerability and the magnitude of PSA responses seen earlier in the program.

The update highlights one particularly striking case that illustrates the therapeutic ceiling of this approach when it works well. A 64‑year‑old with bone metastases and a baseline PSA of 5.4 ng/mL experienced a 95.2% PSA reduction after the first cycle of 67Cu‑SAR‑bisPSMA, then proceeded to three total cycles and ultimately achieved undetectable PSA. Follow‑up bone scan and CT imaging showed no metastatic disease, and this deep responder reported excellent quality of life with only Grade 1, predominantly gastrointestinal, adverse events and no haematological or renal toxicity. As always, single‑patient anecdotes do not redefine standards of care, but in the context of a consistently responsive dataset they provide a clinically intuitive anchor for what this platform may offer selected mCRPC patients.

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