INTRODUCTION The safety and efficacy of bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β "trap") fused to a human IgG1 antibody blocking PD-L1, was evaluated in patients with advanced non-small cell lung cancer (NSCLC). METHODS This expansion cohort of NCT02517398, an ongoing, phase 1, open-label trial, includes 80 patients with advanced NSCLC that progressed following platinum doublet therapy or after platinum-based adjuvant or neoadjuvant treatment who also have not received prior immunotherapy. Patients were randomized 1:1 to receive bintrafusp alfa 500 mg or the recommended phase 2 dose of 1200 mg every 2 weeks. Primary endpoint was best overall response (by RECIST 1.1 as adjudicated by Independent Review Committee) and assessed by objective response rate (ORR). RESULTS Eighty patients were randomized to receive bintrafusp alfa 500 or 1200 mg (n=40 each). Median follow-up was 51.9 weeks (IQR, 19.6-74.0). The ORR in all patients was 21.3% (n=17/80). The ORR was 17.5% (n=7/40) and 25.0% (n=10/40) for the 500-mg dose and the 1200-mg dose (recommended phase 2 dose), respectively. At the 1200-mg dose, patients with PD-L1-positive and PD-L1-high (≥80% expression on tumor cells) had ORRs of 36.0% (n=10/27) and 85.7% (n=6/7), respectively. Treatment-related adverse events (TRAEs) occurred in 55/80 patients (69%) and were grade ≥3 in 23/80 patients (29%). Of 80 patients, 8 (10%) had a TRAE that led to treatment discontinuation, and no treatment-related deaths occurred. CONCLUSIONS Bintrafusp alfa had encouraging efficacy and manageable tolerability in platinum-pre-treated NSCLC patients.

中文翻译：

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Bintrafusp alfa，一种靶向 TGF-β 和 PD-L1 的双功能融合蛋白，用于非小细胞肺癌患者的二线治疗：1 期试验扩展队列的结果

bintrafusp alfa 是一种首创的双功能融合蛋白，由 TGF-βRII 受体（TGF-β“陷阱”）的胞外结构域与阻断 PD-L1 的人 IgG1 抗体融合组成，其安全性和有效性已得到证实。在晚期非小细胞肺癌（NSCLC）患者中进行了评估。方法 NCT02517398 的扩展队列是一项正在进行的 1 期开放标签试验，包括 80 名晚期 NSCLC 患者，这些患者在铂类双联疗法或铂类辅助或新辅助治疗后出现进展，且之前未接受过免疫治疗。患者按照 1:1 的比例随机接受 bintrafusp alfa 500 mg 或每两周 1200 mg 的推荐 2 期剂量。主要终点是最佳总体缓解（根据独立审查委员会判定的 RECIST 1.1）并通过客观缓解率 (ORR) 进行评估。结果 80 名患者被随机分配接受 bintrafusp alfa 500 或 1200 mg（每组 n=40）。中位随访时间为 51.9 周（IQR，19.6-74.0）。所有患者的 ORR 为 21.3% (n=17/80)。500 mg 剂量和 1200 mg 剂量（推荐的 2 期剂量）的 ORR 分别为 17.5% (n=7/40) 和 25.0% (n=10/40)。在 1200 mg 剂量下，PD-L1 阳性和 PD-L1 高（肿瘤细胞表达≥80%）的患者的 ORR 分别为 36.0% (n=10/27) 和 85.7% (n=6/7) ）， 分别。55/80 名患者 (69%) 发生治疗相关不良事件 (TRAE)，23/80 名患者 (29%) 发生 ≥3 级。在 80 名患者中，8 名 (10%) 发生 TRAE 导致治疗停止，并且没有发生与治疗相关的死亡。结论 Bintrafusp alfa 对接受铂类治疗的 NSCLC 患者具有令人鼓舞的疗效和可控的耐受性。