Abstract
177Lu-PSMA-617 (Lu-PSMA-617) is a radiolabelled small-molecule with established efficacy and safety in mCRPC, that delivers β radiation to tumours expressing PSMA. Pembrolizumab, an anti-programmed death 1 inhibitor, has modest single agent anti-tumour activity in mCRPC. We hypothesise that β radiation can induce tumour cell death that is potentially immunogenic, and that addition of pembrolizumab to Lu-PSMA-617 can improve responses. PRINCE aimed to evaluate the safety and efficacy of the combination of Lu-PSMA-617 and pembrolizumab. mCRPC patients (pts) with high PSMA expression without discordant FDG avid disease on paired PSMA and FDG PET/CT scans received up to 6 cycles of Lu-PSMA-617 (6-8 GBq) every 6 weeks in conjunction with 200mg of pembrolizumab every 3 weeks for up to 2 years. Co-primary endpoints were safety and 50% PSA response rate (PSA50-RR). Secondary endpoints included PSA-progression-free survival (PSA-PFS), radiographic PFS (rPFS) and overall survival (OS). 37 pts (median age 72 years; prior docetaxel 73%; prior androgen receptor targeted agent 100%) received a median of 4 cycles of Lu-PSMA-617 and 8 doses of pembrolizumab. Median follow up was 38 weeks. PSA50-RR was 73% (27/37 [95% CI: 56-86]) and 7/9 (78%) pts with RECIST measurable disease had a partial response. rPFS and PSA-PFS at 24 weeks were 64% (95% CI: 45-79) and 68% (95% CI: 50-81) respectively. Common treatment related adverse events (TRAE) (≥10%) were mainly Grade (G) 1-2 and included xerostomia (76%), fatigue (43%), diarrhoea (11%), rash (22%), nausea (24%), elevated ALT (11%), pruritus (19%), and bone pain (11%). Haematologic TRAE included G2-3 anaemia (8%), G1-2 thrombocytopenia (14%), and G1 neutropenia (3%). G3 immune related AEs affecting one pt each included mucosal pemphigus, myasthenia gravis, optic neuritis, pancreatitis, pneumonitis, nephritis, amylase elevation, type 1 diabetes, and colitis in 2 pts. 4 (11%) pts discontinued treatment due to toxicity. The combination of Lu-PSMA-617 and pembrolizumab had promising activity. Toxicities were consistent with those of single agent Lu-PSMA-617 and pembrolizumab.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
