Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignancies.
Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignancies.
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Bintrafusp Alfa是人乳头瘤病毒相关的恶性肿瘤患者的一种双功能融合蛋白，靶向TGF-β和PD-L1。
DOI：
10.1136/jitc-2020-001395
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发表时间：
2020-12
影响因子：
10.9
通讯作者：
Gulley JL
中科院分区：
文献类型：
--
作者：
Strauss J;Gatti-Mays ME;Cho BC;Hill A;Salas S;McClay E;Redman JM;Sater HA;Donahue RN;Jochems C;Lamping E;Burmeister A;Marté JL;Cordes LM;Bilusic M;Karzai F;Ojalvo LS;Jehl G;Rolfe PA;Hinrichs CS;Madan RA;Schlom J;Gulley JL
Bintrafusp alfa是一类双功能融合蛋白，由转化生长因子（TGF）-βRII（一种TGF-β“陷阱”）的胞外结构域与人IgG 1 mAb阻断程序性细胞死亡配体1融合而成。这是对接受bintrafusp alfa治疗的晚期、预治疗的人乳头瘤病毒（HPV）相关恶性肿瘤患者的最大分析。在这些I期（NCT 02517398）和II期试验（NCT 03427411）中，59例晚期、预治疗、检查点载体初治HPV相关癌症患者每2周一次静脉注射bintrafusp alfa，直至疾病进展、不可接受的毒性或停药。主要终点为根据实体瘤疗效评价标准（RECIST）V.1.1的最佳总体缓解;其他终点包括安全性。截至2019年4月17日（I期）和2019年10月4日（II期），在检查点通道初治的全分析人群中，根据RECIST V.1.1确认的客观缓解率为30.5%（95% CI，19.2%至43.9%; 5例完全缓解）; 8例患者病情稳定（疾病控制率，44.1%（95% CI，31.2%至57.6%））。此外，3例患者在初始疾病进展后出现延迟部分缓解，总临床缓解率为35.6%（95% CI，23.6%-49.1%）。另一例外阴癌患者的缓解未经证实。49例患者（83.1%）发生了治疗相关不良事件，其中16例患者（27.1%）为3/4级。未发生给药相关死亡。Bintrafusp alfa显示出临床活性和可管理的安全性，是HPV相关癌症的有希望的治疗方法。这些发现支持进一步研究bintrafusp alfa在晚期、预治疗的HPV相关癌症患者中的作用。
Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor (TGF)-βRII (a TGF-β ‘trap’) fused to a human IgG1 mAb blocking programmed cell death ligand 1. This is the largest analysis of patients with advanced, pretreated human papillomavirus (HPV)-associated malignancies treated with bintrafusp alfa. In these phase 1 (NCT02517398) and phase 2 trials (NCT03427411), 59 patients with advanced, pretreated, checkpoint inhibitor-naive HPV-associated cancers received bintrafusp alfa intravenously every 2 weeks until progressive disease, unacceptable toxicity, or withdrawal. Primary endpoint was best overall response per Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1; other endpoints included safety. As of April 17, 2019 (phase 1), and October 4, 2019 (phase 2), the confirmed objective response rate per RECIST V.1.1 in the checkpoint inhibitor-naive, full-analysis population was 30.5% (95% CI, 19.2% to 43.9%; five complete responses); eight patients had stable disease (disease control rate, 44.1% (95% CI, 31.2% to 57.6%)). In addition, three patients experienced a delayed partial response after initial disease progression, for a total clinical response rate of 35.6% (95% CI, 23.6% to 49.1%). An additional patient with vulvar cancer had an unconfirmed response. Forty-nine patients (83.1%) experienced treatment-related adverse events, which were grade 3/4 in 16 patients (27.1%). No treatment-related deaths occurred. Bintrafusp alfa showed clinical activity and manageable safety and is a promising treatment in HPV-associated cancers. These findings support further investigation of bintrafusp alfa in patients with advanced, pretreated HPV-associated cancers.
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影响因子：
6.4
作者：
de Martel C;Plummer M;Vignat J;Franceschi S
通讯作者：
Franceschi S
DOI：
10.1056/nejmoa1309748
发表时间：
2014-02-20
期刊：
The New England journal of medicine
影响因子：
--
作者：
Tewari KS;Sill MW;Long HJ 3rd;Penson RT;Huang H;Ramondetta LM;Landrum LM;Oaknin A;Reid TJ;Leitao MM;Michael HE;Monk BJ
通讯作者：
Monk BJ
影响因子：
8.8
作者：
Mehra R;Seiwert TY;Gupta S;Weiss J;Gluck I;Eder JP;Burtness B;Tahara M;Keam B;Kang H;Muro K;Geva R;Chung HC;Lin CC;Aurora-Garg D;Ray A;Pathiraja K;Cheng J;Chow LQM;Haddad R
通讯作者：
Haddad R
DOI：
10.1016/s1470-2045(17)30104-3
发表时间：
2017-04
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Morris VK;Salem ME;Nimeiri H;Iqbal S;Singh P;Ciombor K;Polite B;Deming D;Chan E;Wade JL;Xiao L;Bekaii-Saab T;Vence L;Blando J;Mahvash A;Foo WC;Ohaji C;Pasia M;Bland G;Ohinata A;Rogers J;Mehdizadeh A;Banks K;Lanman R;Wolff RA;Streicher H;Allison J;Sharma P;Eng C
通讯作者：
Eng C
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