Talimogene Laherparepvec and Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY-232): A Multicenter, Phase 1b Study
Talimogene Laherparepvec and Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY-232): A Multicenter, Phase 1b Study
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DOI：
10.1158/1078-0432.ccr-20-1170
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发表时间：
2020-10-01
影响因子：
11.5
通讯作者：
Siu, Lillian L.
中科院分区：
文献类型：
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作者：
Harrington, Kevin J.;Kong, Anthony;Siu, Lillian L.
目的：复发性或转移性头颈部鳞状细胞癌(R/M HNSCC)患者预后较差，仅有少数患者受益于检查点免疫治疗。已被批准用于晚期黑色素瘤的溶瘤免疫疗法他立莫吉(T-VEC)与培溴利珠单抗联合使用可能比单用任何一种药物产生更强的抗肿瘤活性。患者和方法：这是一项Ib/III期多中心试验，测试T-VEC瘤内联合静脉注射培溴利珠单抗治疗对铂类化疗无效的R/M HNSCC。对于Ib期，主要终点是剂量限制性毒性(DLT)的发生率。关键的次要终点包括客观缓解率、无进展存活率、总存活率和安全性。结果：36例患者进入Ib期研究。数据截止日为2018年8月28日。中位随访期为5.8个月(0.3~24.2)。报道了一例T-VEC相关的致命性动脉出血的DLT。20例(55.6%)和21例(58.3%)患者发生了与T-VEC和培溴利珠单抗相关的不良事件(AE)。除DLT外，没有与治疗相关的致命不良反应。5例(13.9%)患者部分缓解。10例(27.8%)患者因早期死亡而无法评估疗效。中位PFS和OS分别为3.0个月[95%可信区间(CI)，2.0~5.8]和5.8个月(95%CI，2.9~11.4)。结论：T-VEC和Pembrolizumab联合治疗R/M HNSCC具有较好的安全性。联合用药的疗效与历史上HNSCC研究中单用培溴利珠单抗的疗效相似。这项研究的第三阶段没有进一步进行。
Purpose: The prognosis for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is poor, and only a minority of patients benefit from checkpoint immunotherapy. Talimogene laherparepvec (T-VEC), an oncolytic immunotherapy approved for advanced melanoma, in combination with pembrolizumab may yield enhanced antitumor activity over either agent alone.Patients and Methods: This was a phase Ib/III, multicenter trial testing intratumoral T-VEC combined with intravenous pembrolizumab in R/M HNSCC refractory to platinum-based chemotherapy. For phase Ib, primary endpoint was incidence of dose-limiting toxicity (DLT). Key secondary endpoints included objective response rate and progression-free survival per irRECIST, overall survival, and safety.Results: Thirty-six patients were enrolled into the phase Ib study. The data cut-off date was August 28, 2018. Median follow-up was 5.8 months (range, 0.3-24.2). One DLT of T-VEC-related fatal arterial hemorrhage was reported. Twenty (55.6%) and 21 (58.3%) patients experienced adverse events (AE) related to T-VEC and pembrolizumab, respectively. Besides the DLT, there were no treatment-related fatal AEs. A confirmed partial response was observed in 5 (13.9%) patients. Ten (27.8%) patients were unevaluable for response due to early death. Median PFS and OS were 3.0 months [95% confidence interval (Cl), 2.0-5.8] and 5.8 months (95% Cl, 2.9-11.4), respectively.Conclusions: The combination of T-VEC and pembrolizumab demonstrated a tolerable safety profile in R/M HNSCC. The efficacy with the combination was similar to that with pembrolizumab monotherapy in historical HNSCC studies. Phase III part of this study was not further pursued.