增强对表皮生长因子耗竭免疫疗法的抗体反应：CIMAvax-EGF联合纳武单抗治疗晚期非小细胞肺癌的I期试验结果
Augmenting antibody response to EGF-depleting immunotherapy: Findings from a phase I trial of CIMAvax-EGF in combination with nivolumab in advanced stage NSCLC.
作者信息
Evans Rachel, Lee Kelvin, Wallace Paul K, Reid Mary, Muhitch Jason, Dozier Askia, Mesa Circe, Luaces Patricia L, Santos-Morales Orestes, Groman Adrienne, Cedeno Carlos, Cinquino Aileen, Fisher Daniel T, Puzanov Igor, Opyrchal Mateusz, Fountzilas Christos, Dai Tong, Ernstoff Marc, Attwood Kristopher, Hutson Alan, Johnson Candace, Mazorra Zaima, Saavedra Danay, Leon Kalet, Lage Agustin, Crombet Tania, Dy Grace K
机构信息
Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States.
Department of Medicine Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, United States.
出版信息
Front Oncol. 2022 Aug 3;12:958043. doi: 10.3389/fonc.2022.958043. eCollection 2022.
BACKGROUND
CIMAvax-EGF is an epidermal growth factor (EGF)-depleting immunotherapy which has shown survival benefit as a switch maintenance treatment after platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). The primary objective of this trial is to establish the safety and recommended phase II dose (RP2D) of CIMAvax-EGF in combination with nivolumab as second-line therapy for NSCLC.
METHODS
Patients with immune checkpoint inhibitor-naive metastatic NSCLC were enrolled using a "3+3" dose-escalation design. Toxicities were graded according to CTCAE V4.03. Thirteen patients (one unevaluable), the majority with PD-L1 0%, were enrolled into two dose levels of CIMAvax-EGF.
FINDINGS
The combination was determined to be safe and tolerable. The recommended phase 2 dose of CIMAvax-EGF was 2.4 mg. Humoral response to CIMAvax-EGF was achieved earlier and in a greater number of patients with the combination compared to historical control. Four out of 12 evaluable patients had an objective response.
背景
CIMAvax-EGF是一种消耗表皮生长因子（EGF）的免疫疗法，在晚期非小细胞肺癌（NSCLC）中作为铂类化疗后的转换维持治疗已显示出生存获益。本试验的主要目的是确定CIMAvax-EGF联合纳武单抗作为NSCLC二线治疗的安全性和推荐的II期剂量（RP2D）。
方法
采用“3+3”剂量递增设计纳入未接受过免疫检查点抑制剂治疗的转移性NSCLC患者。毒性按照CTCAE V4.03分级。13例患者（1例不可评估），大多数患者PD-L1为0%，被纳入两个剂量水平的CIMAvax-EGF治疗组。
结果
确定该联合治疗安全且可耐受。CIMAvax-EGF的推荐II期剂量为2.4mg。与历史对照相比，联合治疗时对CIMAvax-EGF的体液反应出现得更早，且有更多患者出现该反应。12例可评估患者中有4例出现客观反应。
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