Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Second-Line Treatment of Patients With NSCLC: Results From an Expansion Cohort of a Phase 1 Trial.
Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Second-Line Treatment of Patients With NSCLC: Results From an Expansion Cohort of a Phase 1 Trial.
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DOI：
10.1016/j.jtho.2020.03.003
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发表时间：
2020-07
期刊：
影响因子：
--
通讯作者：
Cho BC
中科院分区：
文献类型：
--
作者：
Paz-Ares L;Kim TM;Vicente D;Felip E;Lee DH;Lee KH;Lin CC;Flor MJ;Di Nicola M;Alvarez RM;Dussault I;Helwig C;Ojalvo LS;Gulley JL;Cho BC
在晚期NSCLC患者中评价了bintrafusp alfa的安全性和疗效，bintrafusp alfa是一种由转化生长因子β（TGF-β）受体II（TGF-β“陷阱”）的胞外结构域与阻断程序性死亡配体1（PD-L1）的人免疫球蛋白G1抗体融合组成的首个双功能融合蛋白。NCT 02517398的这一扩展队列是一项正在进行的I期开放标签试验，纳入了80例在铂类双药治疗或含铂辅助或新辅助治疗后进展的晚期NSCLC患者，以及既往未接受过免疫治疗的患者。患者以一比一的比例随机接受bintrafusp alfa 500 mg或推荐的II期剂量1200 mg，每2周一次。主要终点是最佳总体缓解（根据独立审查委员会裁定的实体瘤疗效评价标准1.1），并通过客观缓解率（ORR）进行评估。共80例患者随机接受bintrafusp alfa 500或1200 mg（各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%（17/80）。500 mg剂量和1200 mg剂量（推荐的II期剂量）的ORR分别为17.5%（7/40）和25.0%（10/40）。在1200 mg剂量下，PD-L1阳性和PD-L1高（肿瘤细胞表达≥80%）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%）分级为≥ 3级。在80例患者中，8例（10%）发生了导致治疗中止的治疗相关不良事件;未发生治疗相关死亡。Bintrafusp alfa在既往接受过铂类药物治疗的NSCLC患者中具有令人鼓舞的疗效和可管理的耐受性。
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.
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影响因子：
45.3
作者：
Horn, Leora;Spigel, David R.;Eberhardt, Wilfried E. E.
通讯作者：
Eberhardt, Wilfried E. E.
DOI：
10.1016/s1470-2045(16)30364-3
发表时间：
2016-10
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Kaufman HL;Russell J;Hamid O;Bhatia S;Terheyden P;D'Angelo SP;Shih KC;Lebbé C;Linette GP;Milella M;Brownell I;Lewis KD;Lorch JH;Chin K;Mahnke L;von Heydebreck A;Cuillerot JM;Nghiem P
通讯作者：
Nghiem P
影响因子：
3.7
作者：
Morris JC;Tan AR;Olencki TE;Shapiro GI;Dezube BJ;Reiss M;Hsu FJ;Berzofsky JA;Lawrence DP
通讯作者：
Lawrence DP
影响因子：
7.2
作者：
Knudson KM;Hicks KC;Luo X;Chen JQ;Schlom J;Gameiro SR
通讯作者：
Gameiro SR
影响因子：
64.8
作者：
Mariathasan S;Turley SJ;Nickles D;Castiglioni A;Yuen K;Wang Y;Kadel EE III;Koeppen H;Astarita JL;Cubas R;Jhunjhunwala S;Banchereau R;Yang Y;Guan Y;Chalouni C;Ziai J;Şenbabaoğlu Y;Santoro S;Sheinson D;Hung J;Giltnane JM;Pierce AA;Mesh K;Lianoglou S;Riegler J;Carano RAD;Eriksson P;Höglund M;Somarriba L;Halligan DL;van der Heijden MS;Loriot Y;Rosenberg JE;Fong L;Mellman I;Chen DS;Green M;Derleth C;Fine GD;Hegde PS;Bourgon R;Powles T
通讯作者：
Powles T