PRINCE Trial Final Results: Lu-PSMA-617 + Pembrolizumab Shows Deep Responses in Advanced mCRPC

The PRINCE trial has delivered final results showing promise for treating metastatic castration-resistant prostate cancer (mCRPC) with the combination of ¹⁷⁷Lu-PSMA-617 (Pluvicto) and pembrolizumab.
Published in The Lancet Oncology on April 1, 2026 , this single-arm, phase 1b/2 trial enrolled 37 heavily pretreated men (median age 72, 73% prior docetaxel, 100% prior AR inhibitors) who had high PSMA expression on PET/CT and progressive disease. Patients received up to six cycles of ¹⁷⁷Lu-PSMA-617  alongside pembrolizumab 200 mg IV every 3 weeks for up to 24 months, with imaging per PCWG3/RECIST every 12 weeks.

The results were impressive: 76% achieved a PSA50 response (≥50% decline, 95% CI 59-88%), including 46% with PSA90, while objective response rate reached 70% among those with measurable disease (mostly partial responses).
Median PSA progression-free survival hit 8.2 months, radiographic PFS was 11.2 months (40% at 12 months, 16% at 24 months), and overall survival reached 20.8 months (84% at 12 months, 49% at 24 months), outcomes notable in this advanced, low-TMB population suggesting radioligand therapy’s immunogenic priming effect.

Safety remained manageable, dominated by grade 1-2 events like xerostomia (78%), fatigue (46%), nausea (27%), and rash/pruritus (24-27%), with grade 3 immune-related adverse events in 30% (e.g., colitis, fatigue; no grade 4 or deaths). Only 14% discontinued pembrolizumab for toxicity, hematologic effects were mild (3% grade 3 anemia), and quality-of-life measures stayed stable per FACT-P/BPI-SF.

These mature data, building on 2022 ASCO interim findings (then OS 17.8 months at 16 months’ follow-up), underscore the combination’s potential to deepen responses beyond Lu-PSMA-617 monotherapy (VISION trial benchmarks), even without proven pembrolizumab synergy in this design. Experts see PRINCE paving the way for phase 3 radioligand-immunotherapy trials in mCRPC, particularly for PSMA-positive patients post-standard therapies.

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