# ENZA-p

Source: https://nuclide.cc/trials/enza-p/  
Nuclide record `enza-p` (Trial). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

Adding the radioactive drug lutetium-PSMA to the hormone drug enzalutamide, with the dose adjusted according to a mid-treatment PET scan, kept prostate cancer under control for longer and helped men with high-risk metastatic disease live longer than enzalutamide on its own.

## Summary

ENZA-p (ANZUP 1901) was an open-label, randomised, controlled phase 2 trial at 15 Australian hospitals in men with metastatic castration-resistant prostate cancer who had not yet received docetaxel or an androgen receptor pathway inhibitor for mCRPC, had PSMA-PET-positive disease, and carried at least two risk factors for early progression on enzalutamide. Patients received oral enzalutamide alone or with adaptive-dosed intravenous 177Lu-PSMA-617 (two or four cycles of 7.5 GBq every 6-8 weeks, guided by an interim PSMA PET-CT at week 12). The primary endpoint was PSA progression-free survival.

Among 162 randomised patients, adding LuPSMA improved PSA progression-free survival (13.0 vs 7.8 months, HR 0.43, p<0.0001) and PSA response rate (93% vs 68%) at the interim analysis. At longer follow-up (median 34 months), overall survival also favoured the combination (median 34 vs 26 months, HR 0.55, p=0.0053), along with better quality-of-life deterioration-free survival for physical function and overall health. Grade 3-5 adverse events were comparable between arms, with anaemia and thrombocytopenia occurring only in the combination group; there were no treatment-related deaths.

ENZA-p is the first randomised trial to show an overall survival benefit for adding LuPSMA to an ARPI ahead of chemotherapy, using biomarker-guided adaptive dosing via interim PSMA PET, and it has prompted phase 3 evaluation of the same combination strategy.

## Fields

- Kind: Trial
- Status: active
- Last checked: 2026-09-22
- Also known as: ANZUP 1901
- Tags: radioligand therapy; prostate cancer; combination therapy; adaptive dosing
- Registry id: NCT04419402
- Phase: 2
- Setting: Metastatic castration-resistant prostate cancer, PSMA-PET-positive, no prior docetaxel or ARPI for mCRPC, with at least two risk factors for early progression on enzalutamide; first-line mCRPC
- Sponsor: Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
- Enrolled: 162
- Result: Adding adaptive-dosed 177Lu-PSMA-617 to enzalutamide improved PSA progression-free survival (13.0 vs 7.8 months, HR 0.43, p<0.0001) and, at longer follow-up, overall survival (median 34 vs 26 months, HR 0.55, 95% CI 0.36-0.84, p=0.0053) (Lancet Oncology 2024 and 2025)
- Outcomes: PSA progression-free survival: Enzalutamide + adaptive-dosed 177Lu-PSMA-617 13 months vs Enzalutamide alone 7.8 months, HR 0.43; Overall survival (longer follow-up): Enzalutamide + adaptive-dosed 177Lu-PSMA-617 34 months vs Enzalutamide alone 26 months, HR 0.55; PSA response rate (≥50% decline): Enzalutamide + 177Lu-PSMA-617 93% vs Enzalutamide alone 68%; Grade 3-5 adverse events (secondary-outcomes report): Enzalutamide + 177Lu-PSMA-617 46% vs Enzalutamide alone 44%

## Sources

- Lancet Oncology 2024: ENZA-p interim results: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00135-9/abstract
- Lancet Oncology 2025: ENZA-p overall survival and quality of life (secondary outcomes): https://pubmed.ncbi.nlm.nih.gov/39956124/
- ClinicalTrials.gov: NCT04419402: https://clinicaltrials.gov/study/NCT04419402

## Connected records

- drugs: [Enzalutamide](https://nuclide.cc/drugs/enzalutamide/), [Lutetium-177 vipivotide tetraxetan](https://nuclide.cc/drugs/pluvicto/)
- indications: [Metastatic castration-resistant prostate cancer](https://nuclide.cc/indications/prostate-mcrpc/)
- technologies: [PSMA PET](https://nuclide.cc/technologies/psma-pet/)
- trials: [PSMAfore](https://nuclide.cc/trials/psmafore/)
- isotopes: [Lutetium-177](https://nuclide.cc/isotopes/lu-177/)

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