5511 Background: Pembrolizumab was approved for the treatment of recurrent or metastatic cervical cancer, based on 14.3% of objective response rate (ORR) in patients with PD-L1 expression (CPS≥1). GX-188E vaccination has been shown to induce human papillomavirus (HPV) E6- and E7-specific T-cell responses. We aimed to investigate whether a combination of GX-188E (Tirvalimogene teraplasmid) therapeutic DNA vaccine plus pembrolizumab showed antitumor activity against recurrent or advanced cervical cancer. Methods: In this open-label, single-arm, phase 2 trial, patients with recurrent or advanced cervical cancer, who were aged over 18 years with ECOG PS of 0 or 1, HPV-16 or HPV-18 and histologically confirmed positive cervical cancer, and who had progressed after standard-of-care therapy were recruited from nine hospitals in South Korea. Patients received intramuscular 2 mg GX-188E at weeks 1, 2, 4, 7, 13, 19, and optional dose at week 46, and intravenous pembrolizumab 200 mg every 3 weeks for up to 2 years or until disease progression. The primary endpoint was the Best Overall Response Rate assessed by the investigator using RECIST version 1.1. Results: To date, a total of 52 patients have been enrolled and received at least one study treatment, and this interim analysis was performed after obtaining at least one post-baseline tumor assessment data from 48 patients. Median age was 52 (range, 27-79) years and 46.2% had ECOG PS 1. At the data cutoff date on January 11, 2021, median follow-up duration was 6.2 months (range; 1.7- 24.2 months). According to investigator evaluation, 15 (31.3%) of 48 patients achieved best overall response; 5 (10.4 %) patients had a complete response (CR) and 10 (20.8 %) had a partial response (PR). Especially, this combination treatment showed higher response rate, 48.0 %, in patients with PD-L1 positive, HPV-16 and squamous cell carcinoma. Median PFS was 4.1 months (range; 1.3-24.2) and median OS was 16.7 months (range; 1.7-24.2). In this clinical trial with cervical cancer patients, GX-188E in combination with pembrolizumab has shown an improved median PFS and OS than the monotherapy of pembrolizumab (KEYNOTE-158). 17 (32.7%) of 52 patients had treatment-related adverse events of any grade and two (3.8%) had grade 3 or 4 treatment-related adverse events; increased aspartate aminotransferase or alanine aminotransferase. No treatment-related deaths were reported. Conclusions: GX-188E vaccine combined with pembrolizumab in recurrent/advanced cervical cancer was safe and tolerable, and showed an enhanced clinical response rate compared with pembrolizumab alone in particular in patients with PD-L1 positive, HPV-16 and squamous cell carcinoma. The combination therapy could represent a new potential treatment option for this patient population. Clinical trial information: NCT03444376.中文翻译：
GX-188E（一种治疗性 DNA 疫苗）联合 pembrolizumab 治疗 HPV 16 和/或 18 阳性晚期宫颈癌患者的疗效和安全性结果：II 期中期分析结果（KEYNOTE-567）。5511 背景：基于 PD-L1 表达 (CPS≥1) 患者的客观缓解率 (ORR) 为 14.3%，派姆单抗被批准用于治疗复发性或转移性宫颈癌。GX-188E 疫苗接种已显示可诱导人乳头瘤病毒 (HPV) E6 和 E7 特异性 T 细胞反应。我们旨在研究 GX-188E (Tirvalimogene teraplasmid) 治疗性 DNA 疫苗联合 pembrolizumab 是否显示出对复发性或晚期宫颈癌的抗肿瘤活性。方法：在这项开放标签、单臂、2 期试验中，年龄超过 18 岁、ECOG PS 为 0 或 1、HPV-16 或 HPV-18 且组织学证实宫颈癌阳性的复发性或晚期宫颈癌患者从韩国的九家医院招募了癌症，并在标准护理治疗后取得了进展。患者在第 1、2、4、7、13、19 周接受肌肉注射 2 mg GX-188E，并在第 46 周接受可选剂量，以及每 3 周静脉注射派姆单抗 200 mg，持续长达 2 年或直至疾病进展。主要终点是研究者使用 RECIST 1.1 版评估的最佳总体反应率。结果：迄今为止，共有 52 名患者已入组并接受了至少一种研究治疗，该中期分析是在从 48 名患者中获得至少一项基线后肿瘤评估数据后进行的。中位年龄为 52（范围，27-79）岁，46.2% 的 ECOG PS 1。截至 2021 年 1 月 11 日的数据截止日期，中位随访时间为 6.2 个月（范围；1.7-24.2 个月）。根据研究者评估，48 名患者中有 15 名（31.3%）达到最佳总体反应；5（10。4 %) 患者获得完全缓解 (CR)，10 例 (20.8 %) 患者获得部分缓解 (PR)。特别是，这种联合治疗在 PD-L1 阳性、HPV-16 和鳞状细胞癌患者中显示出更高的反应率，达到 48.0 %。中位 PFS 为 4.1 个月（范围；1.3-24.2），中位 OS 为 16.7 个月（范围；1.7-24.2）。在这项针对宫颈癌患者的临床试验中，GX-188E 联合 pembrolizumab 的中位 PFS 和 OS 比 pembrolizumab 的单一疗法 (KEYNOTE-158) 有所改善。52 名患者中有 17 名（32.7%）出现任何级别的治疗相关不良事件，2 名（3.8%）出现 3 级或 4 级治疗相关不良事件；天冬氨酸氨基转移酶或丙氨酸氨基转移酶升高。没有报告与治疗相关的死亡。结论：GX-188E疫苗联合帕博利珠单抗治疗复发/晚期宫颈癌是安全和可耐受的，与单独使用帕博利珠单抗相比，临床反应率提高，特别是在PD-L1阳性、HPV-16和鳞状细胞癌患者中。对于该患者群体，联合疗法可能代表一种新的潜在治疗选择。临床试验资料：NCT03444376。