[177Lu]Lu-PSMA-617 in combination with pembrolizumab for treatment of metastatic castration resistant prostate cancer (PRINCE): a single-arm, phase 1b/2 study
BACKGROUND: Lu]Lu-PSMA-617 with pembrolizumab. METHODS: Lu]Lu-PSMA-617 intravenously every 6 weeks with 200 mg of pembrolizumab intravenously every 3 weeks for up to 24 months. Co-primary endpoints were safety and 50% prostate-specific antigen (PSA) response rate. All participants who received treatment were included in the analysis. The trial is registered with ClinicalTrials.gov, NCT03658447, and has been completed. FINDINGS: Lu]Lu-PSMA-617 and a median of 12 cycles (IQR 6-24) of pembrolizumab. Median follow up was 30 months (IQR 28-31). A decline in PSA of 50% or greater from baseline was observed in 28 (76%, 95% CI 59-88) of the 37 participants. Common treatment-related adverse events were grade 1-2. Grade 3 adverse events included anaemia in one (3%) participant and immune-related adverse events in 11 (30%) participants, including two cases each of fatigue (5%), colitis (5%), and increased serum amylase (5%), and one case (3%) each of pancreatitis, pneumonitis, type 1 diabetes, nephritis, myasthenia gravis, and mucosal pemphigus attributable to pembrolizumab. One participant had co-occurring myasthenia gravis and colitis. There were no grade 4 adverse events or treatment-related deaths. INTERPRETATION: Lu]Lu-PSMA-617 or pembrolizumab, and the combination might provide durable clinical benefit in a subset of patients. FUNDING: Victorian Cancer Agency, Merck Sharp & Dohme, and Novartis.
Authors
- Grace Kong (ORCID: https://orcid.org/0000-0002-0834-6888)
- Sofie H. Tolmeijer (ORCID: https://orcid.org/0000-0003-4066-885X)
- Patricia Banks
- Nadia Hitchen (ORCID: https://orcid.org/0000-0001-9327-4171)
- Mark Scalzo
- Ramin Alipour (ORCID: https://orcid.org/0000-0002-1248-0967)
- Paul J. Neeson (ORCID: https://orcid.org/0000-0002-2729-5887)
- Mathias Bressel (ORCID: https://orcid.org/0000-0002-9718-9596)
- Alexander W. Wyatt (ORCID: https://orcid.org/0000-0003-2399-0329)
- Louise Emmett (ORCID: https://orcid.org/0000-0002-4895-7384)
- Aravind S. Ravi Kumar (ORCID: https://orcid.org/0000-0001-7407-9063)
- James P Buteau (ORCID: https://orcid.org/0000-0001-5693-2913)
- Nicole M. Haynes (ORCID: https://orcid.org/0000-0003-4991-6274)
- A. Antón (ORCID: https://orcid.org/0000-0002-8459-7961)
- Joanna Chan (ORCID: https://orcid.org/0000-0002-0371-1786)
- Narelle Williams (ORCID: https://orcid.org/0000-0002-4426-4900)
- Megan Crumbaker (ORCID: https://orcid.org/0000-0001-7213-900X)
- Nattakorn Dhiantravan (ORCID: https://orcid.org/0000-0003-3188-450X)
- Anupama Pasam
- Timothy Akhurst (ORCID: https://orcid.org/0000-0002-6521-4312)
- A. M. Joshua
- Roslyn E. Wallace
- Rodney John Hicks
- Shahneen Sandhu
- Scott Williams
- Lisa G Horvath
- Erin Cassidy
- Wen Xu
- Michael S Hofman
- Lavinia Spain
Institutions
- Garvan Institute of Medical Research (AU)
- University of British Columbia (CA)
- The University of Melbourne (AU)
- Peter MacCallum Cancer Centre (AU)
- Princess Alexandra Hospital (AU)
- Spinal Cord Injury BC (CA)
- Chris O’Brien Lifehouse (AU)
- St Vincent's Health (AU)
- Eastern Health (AU)
- The Kinghorn Cancer Centre (AU)
- St Vincents Institute of Medical Research (AU)
Publication Details
- Journal
- The Lancet Oncology
- Published
- 2026-03-31
- DOI
- https://doi.org/10.1016/s1470-2045(26)00017-3
- Primary Topic
- Prostate Cancer Treatment and Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Victorian Cancer Agency
- Endocyte
- MSD Australia