Harsini Sara, Soleimani Maryam, Wilson Don, Uribe Carlos, Saprunoff Heather, Bloise Ingrid, Benard Francois
Department of Molecular Imaging and Therapy, BC Cancer, Vancouver, British Columbia, Canada.
Department of Medical Oncology, BC Cancer, Vancouver, British Columbia, Canada; and
J Nucl Med. 2025 Jul 1;66(7):1061-1067. doi: 10.2967/jnumed.124.269064.
Prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals, such as the novel [Lu]Lu-HTK03170, present a promising therapeutic option for metastatic castration-resistant prostate cancer (mCRPC). [Lu]Lu-HTK03170, being used in humans for the first time in this trial, was specifically designed to improve tumor specificity and minimize off-target toxicity, addressing the limitations of existing PSMA radiopharmaceutical therapies. This phase I/II clinical trial aims to evaluate the safety, dosimetry, and efficacy of [Lu]Lu-HTK03170 in patients with PSMA-positive mCRPC who have progressed on androgen receptor pathway inhibitors with or without taxane chemotherapy. This first-in-human, open-label, single-center phase I/II trial is designed to assess the safety and efficacy of [Lu]Lu-HTK03170. Phase I follows a traditional 3 + 3 dose-escalation design to determine the maximum tolerated injected activity of the first injection of [Lu]Lu-HTK03170, followed by personalized dosimetry to calculate the activity of each subsequent injection. Dose-limiting toxicities will be used to guide dose adjustments, with personalized dosimetry used to monitor absorbed doses to critical organs. Up to 18 patients are expected to be enrolled in phase I. Phase II, using a Simon 2-stage design, will evaluate the treatment's efficacy, with approximately 32 patients expected to enroll. Each participant will receive up to 7 treatment cycles administered every 8 wk. In phase I, the primary endpoints include determining the maximum tolerated injected activity and safety profile, which will be assessed by the occurrence of dose-limiting toxicities and the measurement of absorbed doses to normal organs. In phase II, the primary endpoint is the objective response rate as defined by RECIST 1.1. Secondary endpoints include prostate-specific antigen response rate, progression-free survival, overall survival, time to symptomatic skeletal events, and quality of life. Exploratory endpoints include evaluating circulating tumor DNA/RNA as potential biomarkers for treatment response. This ongoing first-in-human trial aims to establish the safety, dosimetry, and preliminary efficacy of [Lu]Lu-HTK03170 in patients with PSMA-positive mCRPC. The results of this study will inform the clinical development of [Lu]Lu-HTK03170 as a potential treatment option for mCRPC.
靶向前列腺特异性膜抗原（PSMA）的放射性药物，如新型的[镥]镥 - HTK03170，为转移性去势抵抗性前列腺癌（mCRPC）提供了一种有前景的治疗选择。[镥]镥 - HTK03170在本次试验中首次用于人体，其专门设计用于提高肿瘤特异性并将非靶向毒性降至最低，以解决现有PSMA放射性药物疗法的局限性。这项I/II期临床试验旨在评估[镥]镥 - HTK03170对在接受或未接受紫杉烷化疗的雄激素受体途径抑制剂治疗后病情进展的PSMA阳性mCRPC患者的安全性、剂量学和疗效。 这项首次人体、开放标签、单中心的I/II期试验旨在评估[镥]镥 - HTK03170的安全性和疗效。I期遵循传统的3 + 3剂量递增设计，以确定首次注射[镥]镥 - HTK03170的最大耐受注射活度，随后进行个体化剂量学计算以确定后续每次注射的活度。剂量限制毒性将用于指导剂量调整，个体化剂量学用于监测关键器官的吸收剂量。预计I期将招募多达18名患者。II期采用西蒙2阶段设计，将评估该治疗的疗效，预计将招募约32名患者。每位参与者将接受每8周一次的多达7个治疗周期。在I期，主要终点包括确定最大耐受注射活度和安全性概况，这将通过剂量限制毒性的发生以及正常器官吸收剂量的测量来评估。在II期，主要终点是根据RECIST 1.1定义的客观缓解率。次要终点包括前列腺特异性抗原缓解率、无进展生存期、总生存期、有症状骨骼事件发生时间和生活质量。探索性终点包括评估循环肿瘤DNA/RNA作为治疗反应的潜在生物标志物。 这项正在进行的首次人体试验旨在确定[镥]镥 - HTK03170对PSMA阳性mCRPC患者的安全性、剂量学和初步疗效。本研究结果将为[镥]镥 - HTK03170作为mCRPC潜在治疗选择的临床开发提供信息。
