# 177Lu-PSMA-617 (Pluvicto) with olaparib

Source: https://nuclide.cc/pairings/pluvicto-plus-olaparib/  
Nuclide record `pluvicto-plus-olaparib` (Pairing). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

An early trial gave the prostate cancer radiotherapy Pluvicto together with the tablet olaparib, on the idea that the pill makes the radiation harder for the cancer cell to repair. Most men's PSA fell, but this is still a small early-stage study, not proof it helps people live longer.

## Summary

LuPARP (NCT03874884) is a phase 1 dose-escalation and dose-expansion trial run by Sandhu, Joshua, Emmett and colleagues (Peter MacCallum Cancer Centre and collaborators) combining 177Lu-PSMA-617 (7.4 GBq every 6 weeks, up to 6 cycles) with olaparib at doses from 50 mg to 300 mg twice daily, given on varying schedules relative to the radioligand infusion. The rationale is mechanistic: 177Lu-PSMA-617 causes single-strand DNA breaks that are normally repaired through PARP-dependent base-excision repair, and PARP inhibition is intended to convert these into lethal double-strand breaks, radiosensitising the tumour irrespective of BRCA or other homologous-recombination-repair status.

Across the 48 enrolled patients with mCRPC previously treated with an androgen-receptor pathway inhibitor and docetaxel, no dose-limiting toxicities were reported and the recommended phase 2 dose was set at olaparib 300 mg twice daily on days -4 to 18 of each 6-week cycle. In the overall cohort, the PSA50 response rate was 66% and PSA90 was 44%, with an objective response rate of 78% by RECIST v1.1 (comparable to, and in the PSA90 measure slightly higher than, the single-agent benchmarks from TheraP and VISION). Hematologic grade 3 toxicity was low (anaemia, neutropenia and thrombocytopenia each in the single digits of percent) and no patient discontinued for toxicity.

This is dose-finding, single-arm evidence in a heavily pre-treated population, not a randomised comparison, so it cannot show whether adding olaparib improves survival or response over 177Lu-PSMA-617 alone; a randomised phase 2 component was being planned as of the 2023 report. Trials of 225Ac-PSMA-I&T plus olaparib (e.g. NCT06909825) are testing the same radiosensitisation idea with an alpha emitter.

## Fields

- Kind: Pairing
- Last checked: 2026-09-22
- Tags: prostate cancer; PARP inhibitor; early phase
- Pairs: Lutetium-177 vipivotide tetraxetan + Olaparib
- Type: combination
- Rationale: 177Lu-PSMA-617 causes single-strand DNA breaks that are normally repaired through PARP-dependent base-excision repair; adding a PARP inhibitor is intended to convert these into lethal double-strand breaks and radiosensitise the tumour.
- Evidence: LuPARP phase 1 trial (NCT03874884, n=48 mCRPC): no dose-limiting toxicities, recommended phase 2 dose olaparib 300 mg BD days -4 to 18; PSA50 66%, PSA90 44%, RECIST objective response rate 78% (Sandhu et al., ASCO 2023).

## Sources

- LuPARP phase 1 abstract (Sandhu et al., ASCO 2023, J Clin Oncol 41:5005): https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.5005
- UroToday conference summary of LuPARP results and comparison with TheraP/VISION: https://www.urotoday.com/conference-highlights/asco-2023/asco-2023-prostate-cancer/144916-asco-2023-luparp-phase-1-trial-of-177lu-psma-617-and-olaparib-in-patients-with-metastatic-castration-resistant-prostate-cancer-mcrpc.html
- ClinicalTrials.gov: NCT03874884 (LuPARP): https://clinicaltrials.gov/study/NCT03874884

## Connected records

- indications: [Metastatic castration-resistant prostate cancer](https://nuclide.cc/indications/prostate-mcrpc/)
- targets: [PARP](https://nuclide.cc/targets/parp/)
- technologies: [Radioligand plus DNA-repair inhibitor combinations](https://nuclide.cc/technologies/radionuclide-parp-combination/)
- people: [Louise Emmett](https://nuclide.cc/people/louise-emmett/), [Shahneen Sandhu](https://nuclide.cc/people/sandhu-shahneen/)
- isotopes: [Actinium-225](https://nuclide.cc/isotopes/ac-225/), [Lutetium-177](https://nuclide.cc/isotopes/lu-177/)
- drugs: [Lutetium-177 vipivotide tetraxetan](https://nuclide.cc/drugs/pluvicto/), [Olaparib](https://nuclide.cc/drugs/olaparib/)

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