Improved efficacy of pembrolizumab combined with soluble EphB4-albumin in HPV-negative EphrinB2 positive head neck squamous cell carcinoma.

Q2 Medicine Oncotarget Pub Date : 2024-07-10 DOI:10.18632/oncotarget.28605
Alexandra Jackovich, Barbara J Gitlitz, Justin Wayne Wong Tiu-Lim, Vinay Duddalwar, Kevin George King, Anthony B El-Khoueiry, Jacob Stephen Thomas, Denice Tsao-Wei, David I Quinn, Parkash S Gill, Jorge J Nieva
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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.

Discussion: The combination of sEphB4-HSA and pembrolizumab has a favorable toxicity profile and favorable activity particularly among HPV-negative EphrinB2 positive patients with HNSCC.

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pembrolizumab联合可溶性EphB4-白蛋白对HPV阴性EphrinB2阳性头颈部鳞状细胞癌的疗效提高。
研究目的经过初次局部治疗后复发或转移的头颈部鳞状细胞癌(HNSCC)患者对西妥昔单抗、全身化疗或检查点抑制剂治疗的反应率较低。有可能改善 HNSCC 患者预后的新型联合疗法是一个尚未满足大量需求的领域:这是一项II期单臂临床试验,研究对象为局部晚期或转移性HNSCC患者,在接受铂类化疗和最多两线治疗后,使用可溶性EphB4-人血清白蛋白(sEphB4-HSA)融合蛋白和pembrolizumab联合治疗。主要终点是安全性和耐受性,主要疗效终点是总反应率(ORR)。次要终点包括无进展生存期(PFS)和总生存期(OS)。HPV状态和EphrinB2表达也是评估疗效的指标:共有 25 名患者入组。中位随访时间为 40.4 个月(9.8 - 40.4 个月)。有 6 例应答者(ORR 24%)。11例HPV阴性和EphrinB2阳性患者中有5例应答(ORR 45%),其中2例患者获得完全应答(CR)。HPV阴性/EphrinB2阳性患者的中位PFS为3.2个月(95% CI为1.1-7.3)。HPV阴性/EphrinB2阳性患者的中位OS为10.9个月(95% CI为2.0-13.7)。高血压、转氨酶和疲劳是最常见的毒性反应:讨论:sEphB4-HSA和pembrolizumab联合用药具有良好的毒性和活性,尤其是在HPV阴性EphrinB2阳性的HNSCC患者中。
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来源期刊
Oncotarget
Oncotarget Oncogenes-CELL BIOLOGY
CiteScore
6.60
自引率
0.00%
发文量
129
审稿时长
1.5 months
期刊介绍: Information not localized
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