Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
Division of Medical Oncology, University of Southern California, Los Angeles, CA 90007, USA.
Oncotarget. 2024 Jul 10;15:444-458. doi: 10.18632/oncotarget.28605.
Patients with relapsed or metastatic head and neck squamous cell carcinoma (HNSCC) after primary local therapy have low response rates with cetuximab, systemic chemotherapy or check point inhibitor therapy. Novel combination therapies with the potential to improve outcomes for patients with HNSCC is an area of high unmet need.
This is a phase II single-arm clinical trial of locally advanced or metastatic HNSCC patients treated with a combination of soluble EphB4-human serum albumin (sEphB4-HSA) fusion protein and pembrolizumab after platinum-based chemotherapy with up to 2 prior lines of treatment. The primary endpoints were safety and tolerability and the primary efficacy endpoint was overall response rate (ORR). Secondary endpoints included progression free survival (PFS) and overall survival (OS). HPV status and EphrinB2 expression were evaluated for outcome.
Twenty-five patients were enrolled. Median follow up was 40.4 months (range 9.8 - 40.4). There were 6 responders (ORR 24%). There were 5 responders in the 11 HPV-negative and EphrinB2 positive patients, (ORR 45%) with 2 of these patients achieving a complete response (CR). The median PFS in HPV-negative/EphrinB2 positive patients was 3.2 months (95% CI 1.1, 7.3). Median OS in HPV-negative/EphrinB2 positive patients was 10.9 months (95% CI 2.0, 13.7). Hypertension, transaminitis and fatigue were the most common toxicities.
The combination of sEphB4-HSA and pembrolizumab has a favorable toxicity profile and favorable activity particularly among HPV-negative EphrinB2 positive patients with HNSCC.
接受过原发性局部治疗后复发或转移性头颈部鳞状细胞癌（HNSCC）的患者，使用西妥昔单抗、系统化疗或检查点抑制剂治疗的反应率较低。对于 HNSCC 患者，有潜力改善治疗效果的新型联合治疗是一个高度未满足的需求领域。
这是一项针对局部晚期或转移性 HNSCC 患者的 II 期单臂临床试验，这些患者在铂类化疗后接受可溶性 EphB4-人血清白蛋白（sEphB4-HSA）融合蛋白和 pembrolizumab 联合治疗，最多接受过 2 线治疗。主要终点是安全性和耐受性，主要疗效终点是总缓解率（ORR）。次要终点包括无进展生存期（PFS）和总生存期（OS）。评估 HPV 状态和 EphrinB2 表达与结局的关系。
共纳入 25 例患者。中位随访时间为 40.4 个月（范围 9.8-40.4）。有 6 例患者应答（ORR 24%）。在 11 例 HPV 阴性和 EphrinB2 阳性患者中，有 5 例（ORR 45%）应答，其中 2 例患者达到完全缓解（CR）。HPV 阴性/EphrinB2 阳性患者的中位 PFS 为 3.2 个月（95%CI 1.1, 7.3）。HPV 阴性/EphrinB2 阳性患者的中位 OS 为 10.9 个月（95%CI 2.0, 13.7）。高血压、转氨血症和疲劳是最常见的毒性反应。
sEphB4-HSA 和 pembrolizumab 的联合治疗具有良好的毒性特征，在 HPV 阴性 EphrinB2 阳性的 HNSCC 患者中具有较好的活性。
