本多中心、开放标签、Ib/II期临床试验评估了胰岛素样生长因子（IGF）1/2中和抗体xentuzumab加艾赛替胺治疗转移性去势抵抗的前列腺癌（mCRPC）。该试验包括Ib期逐步增加和扩大部分以及随机分组的II期部分，对比艾赛替胺单独治疗。Ib期逐步增加、Ib期扩大和II期部分的主要终点是最大可耐受剂量（MTD）、前列腺特异性抗原反应和调查员评估的无进展生存期（PFS）。Ib期逐步增加和II期部分患者在多塞他赛/阿比特龙治疗后或疾病进展后。在Ib期逐步增加阶段（n = 10），未报告剂量限制性毒性，确定xentuzumab每周1000mg加艾赛替胺每日160mg（Xe1000+En160）为MTD并建议进行II期剂量。在Ib期扩大阶段（n = 24），中位PFS为8.2个月，并且有一名患者出现持久反应。在II期（n = 86）中，Xe1000+En160和En160组的中位PFS分别为7.4和6.2个月。亚组分析显示，对IGF1 mRNA或PTEN蛋白水平较高的患者采用Xe1000+En160组有可能受益。总体而言，该联合治疗方案耐受性良好。无选择性的mCRPC患者中，xentuzumab加艾赛替胺的耐受性良好，但缺乏抗肿瘤活性。EudraCT编号2013-004011-41。© 2023. 作者。

This multicentre, open-label, Phase Ib/II trial evaluated the insulin-like growth factor (IGF) 1/2 neutralising antibody xentuzumab plus enzalutamide in metastatic castrate-resistant prostate cancer (mCRPC).The trial included Phase Ib escalation and expansion parts and a randomised Phase II part versus enzalutamide alone. Primary endpoints in the Phase Ib escalation, Phase Ib expansion and Phase II parts were maximum tolerated dose (MTD), prostate-specific antigen response and investigator-assessed progression-free survival (PFS), respectively. Patients in the Phase Ib escalation and Phase II parts had progressed on/after docetaxel/abiraterone.In the Phase Ib escalation (n = 10), no dose-limiting toxicities were reported, and xentuzumab 1000 mg weekly plus enzalutamide 160 mg daily (Xe1000 + En160) was defined as the MTD and recommended Phase 2 dose. In the Phase Ib expansion (n = 24), median PFS was 8.2 months, and one patient had a confirmed, long-term response. In Phase II (n = 86), median PFS for the Xe1000 + En160 and En160 arms was 7.4 and 6.2 months, respectively. Subgroup analysis suggested trends towards benefit with Xe1000 + En160 in patients whose tumours had high levels of IGF1 mRNA or PTEN protein. Overall, the combination was well tolerated.Xentuzumab plus enzalutamide was tolerable but lacked antitumour activity in unselected patients with mCRPC.EudraCT number 2013-004011-41.© 2023. The Author(s).