HI2O-CNIO Haematological Malignancies Clinical Research Unit (Hospital Universitario 12 de Octubre-CNIO), Universidad Complutense & Ciberonc, Madrid, Spain.
Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
J Thorac Oncol. 2020 Jul;15(7):1210-1222. doi: 10.1016/j.jtho.2020.03.003. Epub 2020 Mar 13.
The safety and efficacy of bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the transforming growth factor β (TGF-β) receptor II (a TGF-β "trap") fused to a human immunoglobulin G1 antibody blocking programmed death-ligand 1 (PD-L1), was evaluated in patients with advanced NSCLC.
This expansion cohort of NCT02517398, an ongoing, phase 1, open-label trial, includes 80 patients with advanced NSCLC that progressed after platinum doublet therapy or after platinum-based adjuvant or neoadjuvant treatment and those who also have not received previous immunotherapy. Patients were randomized at a one-to-one ratio to receive either bintrafusp alfa 500 mg or the recommended phase 2 dosage of 1200 mg every 2 weeks. The primary end point was the best overall response (by Response Evaluation Criteria in Solid Tumors 1.1 as adjudicated by independent review committee) and was assessed by the objective response rate (ORR).
A total of 80 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% (17 of 80). The ORR was 17.5% (seven of 40) and 25.0% (10 of 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% (10 of 27) and 85.7% (six of seven), respectively. Treatment-related adverse events occurred in 55 of the 80 patients (69%) and were graded as greater than or equal to 3 in 23 of the 80 patients (29%). Of the 80 patients, eight (10%) had a treatment-related adverse event that led to treatment discontinuation; no treatment-related deaths occurred.
Bintrafusp alfa had encouraging efficacy and manageable tolerability in patients with NSCLC previously treated with platinum.
Bintrafusp alfa 是一种首创的双功能融合蛋白，由转化生长因子 β（TGF-β）受体 II 的细胞外结构域（TGF-β“陷阱”）与阻断程序性死亡配体 1（PD-L1）的人免疫球蛋白 G1 抗体融合而成，在晚期 NSCLC 患者中进行了评估。
本研究为 NCT02517398 的扩展队列，该试验是一项正在进行的、1 期、开放标签试验，纳入了 80 例铂类双药治疗后进展或铂类辅助或新辅助治疗后进展的晚期 NSCLC 患者，且这些患者也未接受过免疫治疗。患者按 1:1 的比例随机接受 bintrafusp alfa 500mg 或推荐的 2 期剂量 1200mg 每 2 周一次。主要终点是最佳总体缓解（由独立审查委员会判定的实体瘤反应评估标准 1.1），并通过客观缓解率（ORR）进行评估。
共有 80 例患者被随机分配至接受 bintrafusp alfa 500mg 或 1200mg（n=40 例）。中位随访时间为 51.9 周（IQR：19.6-74.0）。所有患者的 ORR 为 21.3%（17/80）。500mg 剂量和 1200mg 剂量（推荐的 2 期剂量）的 ORR 分别为 17.5%（7/40）和 25.0%（10/40）。在 1200mg 剂量下，PD-L1 阳性和 PD-L1 高表达（肿瘤细胞表达≥80%）的患者的 ORR 分别为 36.0%（10/27）和 85.7%（6/7）。80 例患者中有 55 例（69%）发生治疗相关不良事件，80 例患者中有 23 例（29%）发生≥3 级治疗相关不良事件。80 例患者中，有 8 例（10%）因治疗相关不良事件而停止治疗；无治疗相关死亡事件发生。
Bintrafusp alfa 在前铂类治疗的 NSCLC 患者中具有令人鼓舞的疗效和可管理的耐受性。
