Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nat Med. 2023 Apr;29(4):898-905. doi: 10.1038/s41591-022-02170-x. Epub 2023 Mar 30.
There is a critical need for effective treatments for leptomeningeal disease (LMD). Here, we report the interim analysis results of an ongoing single-arm, first-in-human phase 1/1b study of concurrent intrathecal (IT) and intravenous (IV) nivolumab in patients with melanoma and LMD. The primary endpoints are determination of safety and the recommended IT nivolumab dose. The secondary endpoint is overall survival (OS). Patients are treated with IT nivolumab alone in cycle 1 and IV nivolumab is included in subsequent cycles. We treated 25 patients with metastatic melanoma using 5, 10, 20 and 50 mg of IT nivolumab. There were no dose-limiting toxicities at any dose level. The recommended IT dose of nivolumab is 50 mg (with IV nivolumab 240 mg) every 2 weeks. Median OS was 4.9 months, with 44% and 26% OS rates at 26 and 52 weeks, respectively. These initial results suggest that concurrent IT and IV nivolumab is safe and feasible with potential efficacy in patients with melanoma LMD, including in patients who had previously received anti-PD1 therapy. Accrual to the study continues, including in patients with lung cancer. ClinicalTrials.gov registration: NCT03025256 .
治疗脑膜疾病（LMD）需要有效的治疗方法。在这里，我们报告了一项正在进行的单臂、首例人体 1/1b 期研究的中期分析结果，该研究评估了黑色素瘤和 LMD 患者鞘内（IT）和静脉（IV）纳武利尤单抗联合治疗的安全性和推荐的 IT 纳武利尤单抗剂量。次要终点是总生存期（OS）。在第 1 周期中，患者单独接受 IT 纳武利尤单抗治疗，在随后的周期中加入 IV 纳武利尤单抗。我们使用 5、10、20 和 50mg 的 IT 纳武利尤单抗治疗了 25 名转移性黑色素瘤患者。在任何剂量水平均未观察到剂量限制毒性。推荐的 IT 纳武利尤单抗剂量为每 2 周 50mg（联合 IV 纳武利尤单抗 240mg）。中位 OS 为 4.9 个月，26 周和 52 周时的 OS 率分别为 44%和 26%。这些初步结果表明，鞘内和静脉纳武利尤单抗联合治疗具有安全性和可行性，对于 LMD 黑色素瘤患者具有潜在疗效，包括先前接受过抗 PD1 治疗的患者。该研究正在继续入组，包括肺癌患者。ClinicalTrials.gov 注册号：NCT03025256。
