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Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: The combination of sEphB4-HSA and pembrolizumab has a favorable toxicity profile and favorable activity particularly among HPV-negative EphrinB2 positive patients with HNSCC.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: The combination of sEphB4-HSA and pembrolizumab has a favorable toxicity profile and favorable activity particularly among HPV-negative EphrinB2 positive patients with HNSCC.
摘要：
目的：初次局部治疗后复发或转移性头颈部鳞状细胞癌（HNSCC）的西妥昔单抗反应率低，全身化疗或检查点抑制剂治疗。具有改善HNSCC患者预后的潜力的新型联合疗法是高度未满足需求的领域。
方法：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，该患者接受可溶性EphB4-人血清白蛋白（sEphB4-HSA）融合蛋白和pembrolizumab的组合治疗后铂类化疗，并接受多达2种先前治疗。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表达的结果。
结果：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个反应者（ORR24%）。11例HPV阴性和EphrinB2阳性患者中有5名应答者，（ORR45%），其中2名患者达到完全缓解（CR）。HPV阴性/EphrinB2阳性患者的中位PFS为3.2个月(95%CI1.1,7.3)。HPV阴性/EphrinB2阳性患者的中位OS为10.9个月(95%CI2.0,13.7)。高血压,转氨酶和疲劳是最常见的毒性。
结论：sEphB4-HSA和pembrolizumab的组合具有良好的毒性和良好的活性，特别是在HPV阴性EphrinB2阳性的HNSCC患者中。
方法：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，该患者接受可溶性EphB4-人血清白蛋白（sEphB4-HSA）融合蛋白和pembrolizumab的组合治疗后铂类化疗，并接受多达2种先前治疗。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表达的结果。
结果：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个反应者（ORR24%）。11例HPV阴性和EphrinB2阳性患者中有5名应答者，（ORR45%），其中2名患者达到完全缓解（CR）。HPV阴性/EphrinB2阳性患者的中位PFS为3.2个月(95%CI1.1,7.3)。HPV阴性/EphrinB2阳性患者的中位OS为10.9个月(95%CI2.0,13.7)。高血压,转氨酶和疲劳是最常见的毒性。
结论：sEphB4-HSA和pembrolizumab的组合具有良好的毒性和良好的活性，特别是在HPV阴性EphrinB2阳性的HNSCC患者中。
