Apalutamide

我院正在开展一项“HRS-4357对比新型雄激素受体通路抑制剂用于PSMA阳性的进展性转移性去势抵抗性前列腺癌治疗的随机、开放、对照、多中心III期临床研究”。本研究的主要目的为HRS-4357对比新型雄激素受体通路抑制剂（ARPI）用于PSMA阳性的晚期转移性去势抵抗性前列腺癌（mCRPC）治疗的有效性。       该研究已经通过  浙江省肿瘤医院医学 伦理委员会审核批准。       HRS-4357注射液为天津恒瑞医药有限公司研发的一种经镥[177Lu]标记的PSMA靶点的放射性配体治疗药物，为1类新药，在境内外均未上市。本品预期可以在晚期前列腺癌患者人群中取得相当的临床获益，进一步改善晚期前列腺癌患者的预后。       本研究为随机、开放、对照、多中心III期临床研究，计划在全国50-60家中心，随机入组370例晚期mCRPC受试者。如果您符合以下条件，您可能符合该研究入组要求： 本研究招募受试者的主要条件如下： 1) 男性，年龄≥18岁； 2) 经组织学和/或细胞学证实的前列腺腺癌，且参考现行临床指南诊断为mCRPC； 3) 经PSMA PET/CT确认为至少存在一处PSMA阳性病灶且无PSMA阴性病灶； 4) 既往在HSPC或CRPC背景下接受过第二代ARPI（阿比特龙、 恩扎卢胺、达罗他胺、阿帕他胺或瑞维鲁胺等）且治疗期间仅出现过一次疾病进展（疾病进展定义同入选标准10），且经研究者评估为适合接受更换为另一种ARPI（适合接受阿比特龙或恩扎卢胺），允许既往接受过一代雄激素受体抑制剂治疗（例如比卡鲁胺、氟他胺）；在入选研究时，疾病发生进展。疾病进展定义为受试者血清睾酮处于稳定去势水平的同时，发生下列至少1项以上：①PSA进展：PSA值>1 ng/mL，间隔至少1周，连续2次PSA升高；②影像学进展：出现明确的新发病灶；骨扫描出现2处或以上新发骨病灶；CT或MRI提示病灶进展（RECIST v1.1）。       如果您符合上述的基本条件，经过您的书面同意后，您需要配合进行既往史问诊、体检、实验室检查等。相关检查费用均由申办方支付，如果评估后符合研究方案所有的入选标准，您就可以参加本临床研究。获得如下医疗服务： （1）研究期间的研究药物治疗； （2）研究期间按照方案进行的相关检查。 另外，您有咨询用药期间相关信息的权利和随时退出本研究的权利，您的隐私也将会得到保护。如果您想参加该项临床研究或想了解更多相关信息，可以通过以下方式咨询： 联系地址：  浙江省杭州市半山东路1号（浙江省肿瘤医院）  泌尿外科： 王宗平 门诊时间：周一全天、周三全天 电话：15068167208 汪奇波 门诊时间：周一下午 电话：18768115429 核医学科： 易贺庆 门诊时间：周三全天、周四下午 电话：18257152796 叶雪梅 门诊时间：周四全天  电话：13958151245 科室简介       浙江省肿瘤医院核医学科始建于1972年，是浙江省较早期设立的核医学科之一，省内最早建立起规范化核素治疗病房。现具备完善的放射性核素药物研发、临床转化体系以及多学科的研发和临床转化团队。核医学科目前开展肿瘤核素靶向治疗、核医学功能影像诊断和分子影像诊断、基于肿瘤的核医学相关基础科学研究并承担相关教学、住院医师规范化培训等工作。目前具有博士、硕士学位团队成员40余名，其中高级职称7名。科室开设治疗床位20张，全面开展肿瘤核素治疗，包括分化型甲状腺癌碘-131治疗（累积治疗超过15000人次）、肿瘤骨转移核素内放射治疗、碘-125粒子治疗、镭-223治疗等， 同时开展177Lu-PSMA前列腺癌治疗和177Lu-DOTATATE 等临床试验。科室拥有国际外先进的PET-CT 2台、PET-MR 1台、SPECT/CT 2台、小动物 PET/CT 1台、小动物SPECT/CT 1台、小动物PET/MR 1台以及回旋加速器等多台设备。开展全身骨显像、甲状腺显像、肾动态显像、唾液腺功能显像、心肌功能显像、碘-131全身及断层显像、18F-FDG PET-CT（PET-MR）肿瘤显像等核医学功能和分子影像检查项目。浙江省肿瘤医院核医学科诊疗设备齐全，技术力量雄厚，临床、科研、教学全面发展。

Pfizer (NYSE: PFE) reported positive Phase III results for Talzenan (talazoparib) plus enzalutamide in HRR-mutated metastatic castration-sensitive prostate cancer, marking the first late-stage evidence for a PARP inhibitor combination in this earlier disease setting. The TALAPRO-3 trial met its primary endpoint of radiographic progression-free survival, with an interim analysis suggesting a trend toward improved overall survival. Trial specifics The TALAPRO-3 trial (NCT04821622) is a multicenter, randomized, double-blind, placebo-controlled study that enrolled 599 patients with metastatic castration-sensitive prostate cancer (mCSPC) harboring alterations in one or more of 12 HRR genes. Patients had received no more than three months of androgen deprivation therapy, with or without an approved androgen receptor pathway inhibitor in the mCSPC setting, and were randomized to receive either talazoparib 0.5 mg daily plus enzalutamide 160 mg daily or placebo plus enzalutamide 160 mg daily. Sites spanned the United States, Canada, Europe, South America, and the Asia-Pacific region. The primary endpoint, investigator-assessed radiographic progression-free survival defined by RECIST 1.1 for soft tissue and PCWG3 criteria for bone, was met with a statistically significant reduction in the risk of disease progression or death for the talazoparib enzalutamide combination versus placebo plus enzalutamide. The company reported that the observed hazard ratio exceeded the pre-specified target of 0.63, and that the majority of patients in the trial remained progression-free at the time of analysis. Consistent rPFS benefit was observed across patients whose tumors harbored BRCA alterations and those with non-BRCA HRR gene mutations, according to the data. At the interim analysis, overall survival — a key secondary endpoint — showed what Pfizer described as a strong trend toward improvement, though the data were not yet mature. Benefits were also reported across other secondary endpoints, including objective response rate, duration of response, and time to PSA progression. Pfizer did not disclose the specific hazard ratio, median rPFS values, or the number of events in either arm. The absence of these quantitative details limits independent assessment of the magnitude of benefit, and the full dataset is expected at an upcoming medical congress. The safety profile of the combination was consistent with the known adverse event profiles of each agent and no new safety signals were identified. Combining PARP inhibition with androgen receptor blockade Talazoparib is an oral PARP inhibitor that blocks PARP enzyme activity and traps PARP proteins at sites of DNA damage, leading to the accumulation of double-strand breaks and cell death in tumors deficient in homologous recombination repair. Enzalutamide is an androgen receptor pathway inhibitor that blocks androgen binding, nuclear translocation, and transcriptional activity. The biological rationale for the combination rests on evidence that androgen receptor signaling supports DNA repair in prostate cancer cells; inhibiting this pathway may deepen the vulnerability of HRR-deficient tumors to PARP inhibition. This synthetic lethality concept has been validated in the mCRPC setting through the TALAPRO-2 trial, which led to the FDA approval of the combination in June 2023 for HRR gene-mutated mCRPC. Positioning and context No therapy is currently approved specifically for HRR gene-mutated mCSPC. Standard treatment for mCSPC generally consists of androgen deprivation therapy combined with an androgen receptor pathway inhibitor such as enzalutamide, apalutamide, or abiraterone, or with docetaxel — none of which are tailored to HRR mutation status. PARP inhibitor approvals in prostate cancer, including talazoparib plus enzalutamide and olaparib (Lynparza, AstraZeneca/Merck), are limited to the castration-resistant setting. The TALAPRO-3 results represent the first Phase III readout of a PARP inhibitor combination in mCSPC selected by HRR gene status. Data from the PROpel and MAGNITUDE trials established the activity of olaparib plus abiraterone and niraparib plus abiraterone, respectively, in mCRPC, but neither program has reported Phase III data in the castration-sensitive population with HRR selection. Cross-trial comparisons are limited by differences in study design, patient populations, comparator arms, and disease stage. Approximately 25% of metastatic prostate cancers harbor HRR gene alterations, according to Pfizer, and these patients face a worse prognosis and reduced responsiveness to current standards of care. Data suggest that 50% to 65% of mCSPC patients progress to castration-resistant disease within two years, with HRR-mutated patients at increased risk of early progression. Next steps, regulatory plans Pfizer stated that the TALAPRO-3 results will be submitted for presentation at an upcoming medical congress and discussed with global health authorities to support potential regulatory submissions for expanding the Talzenna indication to this earlier disease stage. The combination of Talzenna plus Xtandi is currently approved in 60 countries for mCRPC, with the US approval granted in June 2023 and the European Commission approval following in January 2024. If the overall survival data mature favorably, the combination could become the first precision therapy approved for HRR gene-mutated metastatic castration-sensitive prostate cancer, a population where no biomarker-directed treatment currently exists. Leave a Reply Cancel reply Your email address will not be published. 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