[177Lu]Lu-PSMA-617 in Patients with Progressive PSMA+ mCRPC Treated With or Without Prior Taxane-Based Chemotherapy: A Phase 2, Open-Label, Single-Arm Trial in Japan.

Background

This Phase 2 trial evaluated the efficacy, tolerability, and safety of [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) in patients with ≥1 measurable lesion and progressive prostate-specific membrane antigen-positive (PSMA+) metastatic castration-resistant prostate cancer (mCRPC) in Japan.

Methods

This study comprises four parts; data from three parts are presented here. Part 1 evaluated safety and tolerability; Parts 2 (post-taxane) and 3 (pre-taxane/taxane-naive) assessed the overall response rate (ORR; primary endpoint), overall survival (OS), radiographic progression-free survival (rPFS), disease control rate (DCR), PFS, and safety; and Part 4 is the expansion part. Patients received 7.4 GBq (±10%) 177Lu-PSMA-617 Q6W for up to six cycles.

Results

Of the 35 patients who underwent a [68Ga]Ga-PSMA-11 (68Ga-PSMA-11) PET/CT scan, 30 received 177Lu-PSMA-617 (post-taxane, n = 12; pre-taxane, n = 18). No dose-limiting toxicity was noted in Part 1 (n = 3). Post- and pre-taxane patients had a median of three and five cycles, respectively. The primary endpoint, ORR, met the pre-specified threshold, with the lower limit of the 90% confidence interval (CI) above the threshold of 5% for post-taxane and 12% for pre-taxane. Post- and pre-taxane patients had an ORR of 25.0% (90% CI: 7.2-52.7) and 33.3% (90% CI: 15.6-55.4), respectively. In post- and pre-taxane patients, the DCR was 91.7% and 83.3%, the median rPFS was 3.71 and 12.25 months, and the median PFS was 3.71 and 5.59 months, respectively. The median OS was 14.42 and 12.94 months in post- and pre-taxane patients, respectively. The most common adverse events were constipation, decreased appetite, decreased platelet count, anemia, and nausea.

Conclusions

The primary endpoint (ORR) was met. The safety profile of 177Lu-PSMA-617 was consistent with the VISION and PSMAfore studies, with no new safety signals in the Japanese patients with mCRPC.