Survival outcomes and subgroup efficacy analysis of Ga-68-NGUL and Lu-177-DGUL (pocuvotide satetraxetan) in patients with mCRPC: Results from a phase 1/2 study.

5117 Background: Ga-68-NGUL and Lu-177-DGUL (Pocuvotide Satetraxetan) is a novel PSMA-targeting radiopharmaceutical. This study reports the survival outcomes and identifies clinical factors associated with therapeutic response in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: In this phase 1/2 study (NCT05547061), mCRPC patients progressing after ARPI treatment received Lu-177-DGUL (200 mCi every 6 weeks, up to 6 cycles). Efficacy was evaluated using both RECIST v1.1 and PCWG3-modified RECIST v1.1. Key endpoints included ORR, overall survival (OS), and radiographic progression-free survival (rPFS). Results: A total of 91 patients were enrolled. Overall Survival: The median OS was 13.31 months (95% CI: 12.02–17.38). The median rPFS was 11.04 months (95% CI: 8.28–14.29) for the entire cohort. Subgroup Analysis by Metastatic Site: Significant differences in ORR were consistently observed across both criteria. Per RECIST v1.1, the ORR was significantly higher in patients with lung metastases (100% vs. 32.43%, p = 0.0144) and lymph node involvement (48.08% vs. 11.54%, p = 0.0015) compared to those without. These findings align with PCWG3-modified RECIST v1.1 results (Lung: 100% vs. 37.84%, p = 0.0252; LN: 51.92% vs. 19.23%, p = 0.0057). Furthermore, the presence of liver metastases was associated with significantly shorter rPFS compared to those without liver involvement, consistently across RECIST v1.1 (median 5.55 vs. 11.04 months; p = 0.0386) and PCWG3-modified criteria (median 2.76 vs. 8.38 months). Impact of Treatment Cycle on ORR and rPFS: Treatment intensity significantly influenced clinical outcomes across both evaluation criteria (all p < 0.0001). For ORR, under RECIST v1.1 criteria, the ORR was 0% for < 4 cycles, 30% for 4 cycles, and 59.46% for > 4 cycles. Similarly, per PCWG3-modified RECIST v1.1, the ORR improved with the number of cycles (0%, 35%, and 67.57%, respectively). For rPFS, under standard RECIST v1.1, the median rPFS increased with the number of cycles: 2.76 months (95% CI: 2.56–2.86), NE (95% CI: 5.55–NE), and 13.34 months (95% CI: 11.04–NE). Per PCWG3-modified RECIST v1.1, the median rPFS also increased consistently (2.66 months [95% CI: 2.56–2.76], 5.55 months [2.73–NE], and 11.04 months [10.18–14.29], respectively). Conclusions: Ga-68-NGUL and Lu-177-DGUL (Pocuvotide Satetraxetan) demonstrates promising survival benefits in mCRPC. The clinical response is particularly robust in patients with lung or lymph node metastases and those completing more treatment cycles. The significant difference in rPFS observed only under PCWG3-modified criteria highlights the importance of using PCWG3-specific assessments in bone-predominant mCRPC. Clinical trial information: NCT05547061 .