Background: Dual PD-1/CTLA-4 inhibition shows promise in various malignancies. The SWOG S1609 DART trial presents initial results of ipilimumab/nivolumab in vulvar cancers. Methods: DART is a prospective/open-label/multicenter (1,016 US sites)/multi-cohort phase II clinical trial of ipilimumab (1mg/kg intravenously every 6 weeks) plus nivolumab (240mg intravenously every 2 weeks). The primary endpoint was objective response rate [ORR, confirmed complete and partial responses (CR and PR, respectively)] per RECISTv1.1; progression-free survival (PFS), overall survival (OS), clinical benefit rate [CBR; overall response plus stable disease (SD) ≥6 months], and toxicity are secondary endpoints. Results: Sixteen evaluable patients (median age, 55.5 years; 0-6 prior therapies; no prior immunotherapy) were analyzed, all of whom had squamous cell carcinoma histology. ORR was 18.8% (3/16), CBR was 25% (4/16), and CBR plus unconfirmed PR rate was 31% (5/16); PFS was 34.1, 16.7. 15.5, 7.2 and 7.0 months for these five patients. The median PFS and OS were 2.2 and 7.6 months. The most common adverse events were diarrhea, fatigue, pruritus, anorexia, and nausea (25%, n=4 each). Grade 3-4 adverse events occurred in 25% of patients (n=4). There was 1 grade 1-2 adverse event (6.7%) that led to discontinuation, and 1 (6.7%) grade 5 death adverse event. Conclusion: Ipilimumab plus nivolumab in vulvar cancers resulted in an objective response in three out of 16 patients, all of whom had durable responses lasting over one year. Notably, two additional patients experienced durable SD and unconfirmed PR. Correlative studies to determine response and resistance markers are ongoing.

中文翻译：

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罕见肿瘤双重抗 CTLA-4 和抗 PD-1 阻断的 II 期篮子试验 （DART） SWOG S1609：外阴癌


背景：双重 PD-1/CTLA-4 抑制在各种恶性肿瘤中显示出前景。SWOG S1609 DART 试验展示了 ipilimumab/nivolumab 治疗外阴癌的初步结果。方法： DART 是一项前瞻性/开放标签/多中心 （1,016 个美国站点）/多队列 II 期临床试验，研究 ipilimumab （1mg/kg，静脉注射，每 6 周一次） 加纳武利尤单抗 （240mg，静脉注射，每 2 周一次）。主要终点是 RECISTv1.1 的客观缓解率 [ORR，确认的完全缓解和部分缓解 （分别为 CR 和 PR）];无进展生存期 （PFS） 、总生存期 （OS） 、临床获益率 [CBR;总缓解加疾病稳定 （SD） ≥6 个月] 和毒性是次要终点。结果： 分析了 16 例可评估的患者 （中位年龄 55.5 岁;0-6 次既往治疗;既往无免疫治疗），均患有鳞状细胞癌组织学。ORR 为 18.8% （3/16），CBR 为 25% （4/16），CBR 加未经证实的 PR 率为 31% （5/16）;PFS 为 34.1 、 16.7。这五名患者分别为 15.5、7.2 和 7.0 个月。中位 PFS 和 OS 分别为 2.2 个月和 7.6 个月。最常见的不良事件是腹泻、疲劳、瘙痒、厌食和恶心 （25%，各 n=4）。3-4 级不良事件发生在 25% 的患者 （n=4）。有 1 例 1-2 级不良事件 （6.7%） 导致停药，1 例 （6.7%） 5 级死亡不良事件。结论： Ipilimumab 联合纳武利尤单抗治疗外阴癌，16 例患者中有 3 例出现客观反应，所有患者均具有持续一年以上的持久反应。值得注意的是，另有 2 例患者经历了持久的 SD 和未经证实的 PR。确定反应和耐药标志物的相关研究正在进行中。