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 received177Lu-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 of177Lu-PSMA-617 was consistent with the VISION and PSMAfore studies, with no new safety signals in the Japanese patients with mCRPC.
背景：本项II期临床试验旨在评估[¹⁷⁷Lu]Lu-PSMA-617（¹⁷⁷Lu-PSMA-617）在日本至少存在一处可测量病灶且病情进展的前列腺特异性膜抗原阳性（PSMA+）转移性去势抵抗性前列腺癌（mCRPC）患者中的疗效、耐受性和安全性。 方法：本研究包含四个部分；本文报告其中三个部分的数据。第一部分评估安全性和耐受性；第二部分（紫杉烷类治疗后）和第三部分（紫杉烷类治疗前/未接受过紫杉烷类治疗）评估总体缓解率（ORR；主要终点）、总生存期（OS）、影像学无进展生存期（rPFS）、疾病控制率（DCR）、无进展生存期（PFS）及安全性；第四部分为扩展部分。患者每6周接受一次7.4 GBq（±10%）的¹⁷⁷Lu-PSMA-617治疗，最多六个周期。 结果：在接受[⁶⁸Ga]Ga-PSMA-11（⁶⁸Ga-PSMA-11）PET/CT扫描的35例患者中，30例接受了¹⁷⁷Lu-PSMA-617治疗（紫杉烷类治疗后组，n=12；紫杉烷类治疗前组，n=18）。第一部分（n=3）未观察到剂量限制性毒性。紫杉烷类治疗后组和紫杉烷类治疗前组患者的中位治疗周期数分别为3个和5个。主要终点ORR达到预设阈值，紫杉烷类治疗后组和紫杉烷类治疗前组的90%置信区间（CI）下限分别高于5%和12%的阈值。紫杉烷类治疗后组和紫杉烷类治疗前组患者的ORR分别为25.0%（90% CI：7.2–52.7）和33.3%（90% CI：15.6–55.4）。两组患者的DCR分别为91.7%和83.3%，中位rPFS分别为3.71个月和12.25个月，中位PFS分别为3.71个月和5.59个月。中位OS分别为14.42个月和12.94个月。最常见的不良事件为便秘、食欲减退、血小板计数下降、贫血和恶心。 结论：主要终点（ORR）已达到。¹⁷⁷Lu-PSMA-617在日本mCRPC患者中的安全性特征与VISION和PSMAfore研究一致，未发现新的安全性信号。
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