医学
转移性尿路上皮癌
内科学
耐受性
彭布罗利珠单抗
临床终点
化疗
养生
胃肠病学
肿瘤科
癌
实体瘤疗效评价标准
毒性
无进展生存期
外科
泌尿科
临床研究阶段
癌症
不利影响
免疫疗法
膀胱癌
尿路上皮癌
临床试验
作者
Sarmad Sadeghi,David I. Quinn,Tanya B. Dorff,Sumanta K. Pal,Susan Groshen,Denice Tsao‐Wei,Rahul Atul Parikh,Michael Devitt,Mamta Parikh,Alexandra Jackovich,Nora Ruel,Nicholas J. Vogelzang,Earle F. Burgess,Imran Siddiqi,Inderbir S. Gill,Primo N. Lara,Robert Dreicer,Parkash S. Gill
摘要
Patients with metastatic urothelial carcinoma have poor prognosis after failure of standard first-line chemotherapy. Immune check point programmed death 1-programmed death ligand 1 antibodies have low response rates and thus there exists a major unmet need.In this phase II trial, patients with metastatic urothelial carcinoma that recurred or progressed after platinum-based chemotherapy received soluble EphB4-human serum albumin (sEphB4-HSA) in combination with pembrolizumab. The primary end points were tolerability and overall survival (OS). The secondary end points were progression-free survival (PFS), objective response rate (ORR), duration of response, and toxicity. The expression of sEphB4-HSA target EphrinB2 was correlated with outcomes.Seventy patients were enrolled. The median follow up was 22.9 months (range, 1.3-54.7). The regimen had acceptable toxicity. In the intent-to-treat analysis (N = 70), the median OS was 14.6 months (95% CI, 9.2 to 21.5). Twenty-six (37%) patients had an objective response (95% CI, 26 to 48). The median PFS was 4.1 (95% CI, 1.5 to 5.7) months. Forty-six (66%) patients expressed EphrinB2, and among them, the median OS was 21.5 months (95% CI, 12.4 to not reached), the ORR was 52% (95% CI, 37 to 67), including a complete response rate of 24% (11 of 46; 95% CI, 12 to 36). The median PFS was 5.7 (95% CI, 2.7 to 27.9) months. Response was maintained at 6, 12, and 24 months in 88%, 74%, and 69% of the patients, respectively.The combination of sEphB4-HSA and pembrolizumab appears synergistic with improved OS and ORR compared with historical data for programmed death 1/programmed death ligand 1 monotherapy.
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