The efficacy and safety of 177 Lu-PSMA-617 in Chinese patients with post-taxane metastatic castration-resistant prostate cancer: From a multicenter phase II study.

181 Background: The global phase III VISION trial established the efficacy of 177 Lu-PSMA-617 in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) who had been previously treated with ≥1 androgen receptor pathway inhibitor (ARPI) and one or two taxane regimens. 177 Lu-PSMA-617, along with Best Standard of Care (BSoC), demonstrated a median radiographic progression-free survival (rPFS) of 8.7 months. Methods: This open-label, multicenter single-arm phase II study (NCT05670106) evaluated 177 Lu-PSMA-617 in Chinese pts with prostate-specific membrane antigen (PSMA)-positive mCRPC who progressed after ≥1 ARPI and 1-2 taxane regimens. The trial employed a two-part design: the Main part enrolled only pts with ≥1 measurable soft tissue lesion at baseline, while the Extension part enrolled additional pts with or without measurable lesions. Pts received 177 Lu-PSMA-617 (7.4 GBq ±10%) every 6 weeks for up to 6 cycles, in addition to BSoC. The primary endpoint was soft tissue overall response rate (ORR) assessed by blinded independent central review (BICR) per PCWG3-modified RECIST v1.1 in the Main part. Secondary endpoints included duration of response (DOR), rPFS, overall survival (OS), prostate-specific antigen (PSA50) response rate, ORR in all pts with measurable lesions, the safety profile and tolerability, health-related quality of life (HRQoL) and the pharmacokinetics (PK) and dosimetry. Results: From June 1, 2023 to January 17, 2024, a total of 62 pts (median age 68.5 years; 72.6% with ≥3 prior ARPI treatments) were enrolled, and 59 received treatment (Main part, n=29; Extension part, n=30). With a median follow-up of 14.29 months, the ORR in the Main part was 41.4% (95% CI: 23.5–61.1%), comparable to VISION trial (AAA617+BSoC arm: 51.1%; BSoC arm: 3.1%). The ORR based on all pts with measurable lesions was 39.2% (95% CI: 25.8-53.9%; n=51). Secondary endpoints in the Main part included a median DOR of 7.69 months (9.8 months in VISION), median rPFS of 6.05 months, median OS of 11.89 months, and PSA50 response rate of 44.8%, confirming the clinically meaningful efficacy in this population. In the safety analysis set (n=59), grade ≥3 treatment-related adverse events (TRAEs) were observed in 44.1% of pts. Treatment-related serious adverse events were reported in 23.7% of pts, and TRAEs leading to treatment discontinuation occurred in 18.6% of pts. The most common grade ≥3 safety topics of interest (≥2%) included myelosuppression (42.4%), hepatotoxicity (8.5%) and renal toxicity (3.4%). No grade 3 dry mouth were observed. These safety findings align with the established safety profile of 177 Lu-PSMA-617. Conclusions: This is the first trial showing the efficacy and safety of 177 Lu-PSMA-617 in Chinese mCRPC pts, supporting its favorable benefit-risk profile when administered with BSoC. Clinical trial information: NCT05670106 .