Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Department of Oncology, University of Oxford, Oxford, UK.
Br J Cancer. 2023 Oct;129(6):965-973. doi: 10.1038/s41416-023-02380-1. Epub 2023 Aug 3.
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.
这项多中心、开放标签、Ib/II 期试验评估了胰岛素样生长因子 (IGF) 1/2 中和抗体 xentuzumab 联合恩扎卢胺在转移性去势抵抗性前列腺癌 (mCRPC) 中的作用。
该试验包括 Ib 期递增和扩展部分以及与恩扎卢胺单独治疗的随机 II 期部分。Ib 期递增、Ib 期扩展和 II 期部分的主要终点分别为最大耐受剂量 (MTD)、前列腺特异性抗原反应和研究者评估的无进展生存期 (PFS)。Ib 期递增和 II 期部分的患者在接受多西他赛/阿比特龙治疗后进展。
在 Ib 期递增部分 (n=10)，未报告剂量限制毒性，xentuzumab 1000mg 每周加恩扎卢胺 160mg 每日 (Xe1000+En160) 被定义为 MTD 和推荐的 II 期剂量。在 Ib 期扩展部分 (n=24)，中位 PFS 为 8.2 个月，1 例患者有确认的长期缓解。在 II 期 (n=86)，Xe1000+En160 和 En160 组的中位 PFS 分别为 7.4 和 6.2 个月。亚组分析表明，在 IGF1 mRNA 或 PTEN 蛋白水平高的患者中，Xe1000+En160 有获益趋势。总体而言，该联合治疗耐受性良好。
xentuzumab 联合恩扎卢胺在未选择的 mCRPC 患者中耐受良好，但缺乏抗肿瘤活性。
EudraCT 编号 2013-004011-41。
