Arora Shaily, Balasubramaniam Sanjeeve, Zhang Wei, Zhang Lijun, Sridhara Rajeshwari, Spillman Dianne, Mathai Jaigi P, Scott Bradley, Golding Sarah J, Coory Michael, Pazdur Richard, Beaver Julia A
Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, Maryland.
Clin Cancer Res. 2020 Oct 1;26(19):5062-5067. doi: 10.1158/1078-0432.CCR-19-3979. Epub 2020 Apr 15.
On September 17, 2019, FDA granted accelerated approval to pembrolizumab plus lenvatinib for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation. The submission and review of this application was conducted through an FDA Oncology Center of Excellence initiative named Project Orbis whereby the FDA, the Australian Therapeutic Goods Administration, and Health Canada were able to simultaneously review and collaborate, rendering simultaneous approval decisions in all countries. Accelerated approval of the pembrolizumab plus lenvatinib combination was based on a single-arm trial of 94 patients, with previously treated metastatic endometrial cancer whose tumors were not MSI-H/dMMR. Efficacy was demonstrated on the basis of an objective response rate of 38.3% (95% confidence interval, 28.5%-48.9%) with 10 complete responses (10.6%) accompanied by supportive durations of response. Trials to confirm clinical benefit of this combination are ongoing. Here, we summarize the benefit-risk analysis supporting accelerated approval of the pembrolizumab plus lenvatinib combination and describe the methodology for the first Project Orbis review.
2019年9月17日，美国食品药品监督管理局（FDA）加速批准帕博利珠单抗联合乐伐替尼用于治疗非微卫星高度不稳定（MSI-H）或错配修复缺陷（dMMR）的晚期子宫内膜癌患者，这些患者在先前的全身治疗后出现疾病进展，但不适合进行根治性手术或放疗。该申请的提交和审查是通过FDA卓越肿瘤中心的一项名为“奥比斯计划”的倡议进行的，通过该倡议，FDA、澳大利亚治疗用品管理局和加拿大卫生部能够同时进行审查和协作，并在所有国家做出同步批准决定。帕博利珠单抗联合乐伐替尼的加速批准基于一项对94例患者的单臂试验，这些患者为先前接受过治疗的转移性子宫内膜癌，其肿瘤并非MSI-H/dMMR。根据客观缓解率38.3%（95%置信区间，28.5%-48.9%）以及10例完全缓解（10.6%）并伴有支持性缓解持续时间，证明了该联合用药的疗效。确认该联合用药临床获益的试验正在进行中。在此，我们总结了支持帕博利珠单抗联合乐伐替尼加速批准的获益-风险分析，并描述了首次“奥比斯计划”审查的方法。
