Purpose Trop-2, expressed in most solid cancers, may be a target for antibody-drug conjugates (ADCs) in non-small-cell lung cancer (NSCLC). We studied sacituzumab govitecan (IMMU-132), a Trop-2 ADC, for the targeting of SN-38. Patients and Methods We evaluated IMMU-132 in a single-arm multicenter trial in patients with pretreated metastatic NSCLC who received either 8 or 10 mg/kg on days 1 and 8 of 21-day cycles. The primary end points were safety and objective response rate (ORR). Progression-free survival and overall survival were secondary end points. Results Fifty-four patients were treated. In the response-assessable study population (n = 47), which had a median of three prior therapies (range, two to seven), the ORR was 19%; median response duration, 6.0 months (95% CI, 4.8 to 8.3 months); and clinical benefit rate (complete response + partial response + stable disease ≥ 4 months), 43%. ORR in the intention-to-treat (ITT) population was 17% (nine of 54). Responses occurred with a median onset of 3.8 months, including patients who had relapsed or progressed after immune checkpoint inhibitor therapy. Median ITT progression-free survival was 5.2 months (95% CI, 3.2 to 7.1 months) and median ITT overall survival, 9.5 months (95% CI, 5.9 to 16.7 months). Grade 3 or higher adverse events included neutropenia (28%), diarrhea (7%), nausea (7%), fatigue (6%), and febrile neutropenia (4%). One patient developed a transient immune response, despite patients receiving a median of 10 doses. More than 90% of 26 assessable archival tumor specimens were highly positive (2+, 3+) for Trop-2 by immunohistochemistry, which suggests that Trop-2 is not a predictive biomarker for response. Conclusion IMMU-132 was well-tolerated and induced durable responses in heavily pretreated patients with metastatic NSCLC. This ADC should be studied further in this disease and in other patients with Trop-2-expressing tumors.

中文翻译：

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使用 SN-38-Anti-Trop-2 药物偶联物 Sacituzumab Govitecan 治疗晚期非小细胞肺癌

目的 Trop-2 在大多数实体癌中表达，可能是非小细胞肺癌 (NSCLC) 中抗体-药物偶联物 (ADC) 的靶标。我们研究了 Sacituzumab govitecan (IMMU-132)，一种 Trop-2 ADC，用于靶向 SN-38。患者和方法 我们在一项单臂多中心试验中评估了 IMMU-132，这些患者在接受 8 或 10 mg/kg 治疗的转移性非小细胞肺癌患者中，在 21 天周期的第 1 天和第 8 天接受了 8 或 10 mg/kg 的治疗。主要终点是安全性和客观反应率（ORR）。无进展生存期和总生存期是次要终点。结果共治疗54例。在可评估反应的研究人群（n = 47）中，先前治疗的中位数为三种（范围，2 到 7 种），ORR 为 19%；中位反应持续时间，6.0 个月（95% CI，4.8 至 8.3 个月）；临床获益率（完全缓解+部分缓解+病情稳定≥4个月）43%。意向治疗 (ITT) 人群的 ORR 为 17%（54 人中有 9 人）。出现反应的中位起始时间为 3.8 个月，包括在免疫检查点抑制剂治疗后复发或进展的患者。中位 ITT 无进展生存期为 5.2 个月（95% CI，3.2 至 7.1 个月），中位 ITT 总生存期为 9.5 个月（95% CI，5.9 至 16.7 个月）。3 级或更高级别的不良事件包括中性粒细胞减少 (28%)、腹泻 (7%)、恶心 (7%)、疲劳 (6%) 和发热性中性粒细胞减少 (4%)。尽管患者接受了 10 个剂量的中位数，但一名患者出现了短暂的免疫反应。通过免疫组织化学，26 个可评估的存档肿瘤标本中超过 90% 对 Trop-2 呈高度阳性（2+、3+），这表明 Trop-2 不是反应的预测生物标志物。结论 IMMU-132 在接受过大量治疗的转移性 NSCLC 患者中具有良好的耐受性并诱导持久的反应。应在该疾病和其他表达 Trop-2 的肿瘤患者中进一步研究该 ADC。