Department of Immunotherapeutics, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan
Department of Immunotherapeutics, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan.
J Immunother Cancer. 2020 Sep;8(2). doi: 10.1136/jitc-2020-001185.
Not all non-small cell lung cancer (NSCLC) patients possess drug-targetable driver mutations, and response rates to immune checkpoint blockade therapies also remain unsatisfactory. Therefore, more effective treatments are still needed. Here, we report the results of a phase 2 clinical trial of adoptive cell therapy using zoledronate-expanded autologous Vγ9Vδ2 T-cells for treatment-refractory NSCLC.
NSCLC patients who had undergone at least two regimens of standard chemotherapy for unresectable disease or had had at least one treatment including chemotherapy or radiation for recurrent disease after surgery were enrolled in this open-label, single-arm, multicenter, phase 2 study. After preliminary testing of Vγ9Vδ2 T-cell proliferation, autologous peripheral blood mononuclear cells were cultured with zoledronate and IL-2 to expand the Vγ9Vδ2 T-cells. Cultured cells (>1×10) were intravenously administered every 2 weeks for six injections. The primary endpoint of this study was progression-free survival (PFS), and secondary endpoints included overall survival (OS), best objective response rate (ORR), disease control rate (DCR), safety and immunomonitoring. Clinical efficacy was defined as median PFS significantly >4 months.
Twenty-five patients (20 adenocarcinoma, 4 squamous cell carcinoma and 1 large cell carcinoma) were enrolled. Autologous Vγ9Vδ2 T-cell therapy was administered to all 25 patients, of which 16 completed the foreseen course of 6 injections of cultured cells. Median PFS was 95.0 days (95% CI 73.0 to 132.0 days); median OS was 418.0 days (179.0-479.0 days), and best overall responses were 1 partial response, 16 stable disease (SD) and 8 progressive disease. ORR and DCR were 4.0% (0.1%-20.4%) and 68.0% (46.5%-85.1%), respectively. Severe adverse events developed in nine patients, mostly associated with disease progression. In one patient, pneumonitis and inflammatory responses resulted from Vγ9Vδ2 T-cell infusions, together with the disappearance of a massive tumor.
Although autologous Vγ9Vδ2 T-cell therapy was well tolerated and may have an acceptable DCR, this trial did not meet its primary efficacy endpoint.
UMIN000006128.
并非所有非小细胞肺癌（NSCLC）患者都具有可靶向药物的驱动突变，免疫检查点阻断疗法的反应率也仍然不尽如人意。因此，仍需要更有效的治疗方法。在这里，我们报告了使用唑来膦酸扩增自体 Vγ9Vδ2 T 细胞进行治疗难治性 NSCLC 的过继细胞治疗的 2 期临床试验结果。
该开放标签、单臂、多中心、2 期研究纳入了至少接受过两种标准化疗方案治疗不可切除疾病的 NSCLC 患者，或在手术后至少接受过一次包括化疗或放疗在内的治疗后复发的患者。在初步检测 Vγ9Vδ2 T 细胞增殖后，用唑来膦酸和 IL-2 培养自体外周血单核细胞以扩增 Vγ9Vδ2 T 细胞。培养的细胞（>1×10）每 2 周静脉注射一次，共 6 次。该研究的主要终点是无进展生存期（PFS），次要终点包括总生存期（OS）、最佳客观缓解率（ORR）、疾病控制率（DCR）、安全性和免疫监测。临床疗效定义为中位 PFS 显著>4 个月。
共纳入 25 例患者（20 例腺癌、4 例鳞癌和 1 例大细胞癌）。所有 25 例患者均接受了自体 Vγ9Vδ2 T 细胞治疗，其中 16 例完成了预期的 6 次培养细胞注射疗程。中位 PFS 为 95.0 天（95%CI 73.0-132.0 天）；中位 OS 为 418.0 天（179.0-479.0 天），最佳总体反应为 1 例部分缓解，16 例疾病稳定（SD）和 8 例疾病进展。ORR 和 DCR 分别为 4.0%（0.1%-20.4%）和 68.0%（46.5%-85.1%）。9 例患者发生严重不良事件，大多与疾病进展有关。在 1 例患者中，Vγ9Vδ2 T 细胞输注后出现肺炎和炎症反应，同时大量肿瘤消失。
尽管自体 Vγ9Vδ2 T 细胞治疗耐受性良好，DCR 可能可以接受，但本试验未达到主要疗效终点。
UMIN000006128。
