PSMAfore is the trial where Lu-PSMA (PLUVICTO) went into earlier stage (pre chemo). The responses were better in that pre-chemo group than in the later stage group that VISION trialed. So, SECURE has replicated that and helped create and clarify that separation. I think we will still go after the post chemo groups separately as well since treatment in those groups was still very good. I think its going to be similar to CLARIFY (pre-definitive treatment / prostatectomy etc.) and AMPLIFY (recurrence post definitive treatment).
Next step - its the earlier group: One thing to look out for this time is the combination of 67Cu-SAR-bisPSMA with enzalutamide! In theory (called the clonal adjustment theory) - this should be more effective than using either product alone! In ENZA -p the combination of Lu-PSMA + enzalutamide was associated with significant improvements all round, including Radiographic PFS (HR: 0.67), PSA50 (93% versus 68%), PSA90 (78% versus 37%) (ESMO 2023), as well as overall survival as recently reported at ASCO GU 2025 (shown in the image below).
Another great thing about this group that we are targeting is that it is much larger (Clarity ASX Ann): great for trials and and revenue later.
----- The clonal adjustment theory: Studies have shown that androgen deprivation therapy (ADT) and ARPIs like enzalutamide increase PSMA expression in prostate cancer cells. Further, the clonal adjustment theory suggests that Enzalutamide forces the selection of androgen-resistant clones, which compensate by increasing PSMA expression, making them more susceptible to therapies like Pluvicto! ENZA-p has confirmed improvement in efficacy, so there is no reason to expect less from 67Cu-Sar-bisPSMA). -----
REFS
ESMO 2023: Enzalutamide and 177Lu-PSMA-617 in Poor-Risk Metastatic Castration-Resistant Prostate Cancer (mCRPC), a Randomized, Phase 2 Trial; https://www.urotoday.com/conference-highlights/esmo-2023/esmo-2023-prostate-cancer/147459-esmo-2023-enza-p-anzup-1901-enzalutamide-and-177lu-psma-617-in-poor-risk-metastatic-castration-resistant-prostate-cancer-mcrpc-a-randomized-phase-2-trial.html
ASCO GU 2025: Overall Survival and Quality of Life with 177Lu-PSMA-617 plus Enzalutamide Versus Enzalutamide Alone in Poor-Risk mCRPC in ENZA-P (ANZUP 1901); https://www.urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-prostate-cancer/158212-asco-gu-2025-overall-survival-and-quality-of-life-with-177lu-psma-617-plus-enzalutamide-versus-enzalutamide-alone-in-poor-risk-mcrpc-in-enza-p-anzup-1901.html
ASX Ann: Clarity receives US FDA Fast Track Designation for the treatment of metastatic castration-resistant prostate cancer patients with Cu-67 SAR-bisPSMA; https://www.claritypharmaceuticals.com/news/ftd-67cu-sarbispsma/
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