Lim Myong Cheol, Choi Youn Jin, Hur Soo-Young, Kim Yong-Man, No Jae Hong, Kim Byoung-Gie, Cho Chi Heum, Kim Sung Hoon, Jeong Dae Hoon, Lee Jae-Kwan, Kim Ji Hyun, Choi Yoon-Jeong, Woo Jung Won, Sung Young Chul, Park Jong Sup
National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea.
Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
EClinicalMedicine. 2024 Jul 13;74:102716. doi: 10.1016/j.eclinm.2024.102716. eCollection 2024 Aug.
In an interim analysis of this phase 2 trial, adding the GX-188E vaccine to pembrolizumab resulted in manageable toxicity with antitumor activities in patients with recurrent or advanced cervical cancer. Here, we report the final safety and efficacy results after a long-term follow-up at the study's completion.
This open-label, single-arm, phase II trial was conducted in nine hospitals in South Korea (ClinicalTrials.gov identifier, NCT03444376). Eligible patients were aged ≥18 years with recurrent or advanced inoperable cervical cancer, Eastern Cooperative Oncology Group Performance status of 0 or 1, and positivity for HPV 16/18, who failed the available standard-of-care therapy. Patients received intramuscular 2 mg GX-188E at weeks 1, 2, 4, 7, 13, 19, and 46 and intravenous 200 mg pembrolizumab every 3 weeks for up to 2 years or until disease progression. The primary endpoint was the objective response rate (ORR) within 24 weeks.
Between June 19, 2018, and December 24, 2021, 65 patients were enrolled and received at least one dose of the study treatment. Sixty patients received combination treatment with GX-188E and pembrolizumab and underwent efficacy analysis. After a median follow-up of 14.72 months, the confirmed ORR was 35.0% (95% CI, 23.1-48.4). Five patients (8.3%) had a complete response, and 16 (26.7%) had a partial response. In addition, patients with PD-L1-positive and PD-L1-negative tumors had an ORR of 38.9% (95% CI, 23.1-56.5) and 29.2% (95% CI, 12.6-51.1), respectively. The median duration of response of all the patients was 12.3 months (95% CI, 5.3-not reached [NR]). For those with PD-L1-positive tumors, it was 12.3 months (95% CI, 3.5-NR), and for those with PD-L1-negative tumors, it was NR (95% CI, 2.4-NR). The median progression-free survival of the 60 patients was 4.4 months (95% CI, 2.1-8.3), and the median overall survival was 23.8 months (95% CI, 14.0-NR). 22 (33.8%) of 65 patients had treatment-related adverse events (TRAEs) of any grade and four (6.2%) had grade 3-4 TRAEs. No treatment-related deaths occurred.
The GX-188E vaccine combined with pembrolizumab in recurrent or advanced HPV-positive cervical cancer was safe and showed a promising overall survival and clinical response rate. This combination therapy might provide a new potential treatment option for patients with recurrent or advanced cervical cancer.
National Cancer Center Onco-Innovation Unit, Korea.
在这项2期试验的中期分析中，对于复发性或晚期宫颈癌患者，在帕博利珠单抗基础上加用GX-188E疫苗可产生可控的毒性，并具有抗肿瘤活性。在此，我们报告研究完成后的长期随访最终安全性和疗效结果。
这项开放标签、单臂、2期试验在韩国的9家医院进行（ClinicalTrials.gov标识符，NCT03444376）。符合条件的患者年龄≥18岁，患有复发性或晚期无法手术的宫颈癌，东部肿瘤协作组体能状态为0或1，且HPV 16/18呈阳性，这些患者对现有的标准治疗方案无效。患者在第1、2、4、7、13、19和46周接受2mg GX-188E肌肉注射，每3周接受200mg帕博利珠单抗静脉注射，持续2年或直至疾病进展。主要终点是24周内的客观缓解率（ORR）。
在2018年6月19日至2021年12月24日期间，65例患者入组并接受了至少一剂研究治疗。60例患者接受了GX-188E与帕博利珠单抗的联合治疗并进行了疗效分析。中位随访14.72个月后，确认的ORR为35.0%（95%CI，23.1-48.4）。5例患者（8.3%）完全缓解，16例（26.7%）部分缓解。此外，PD-L1阳性和PD-L1阴性肿瘤患者的ORR分别为38.9%（95%CI，23.1-56.5）和29.2%（95%CI，12.6-51.1）。所有患者缓解的中位持续时间为12.3个月（95%CI，5.3-未达到[NR]）。对于PD-L1阳性肿瘤患者，为12.3个月（95%CI，3.5-NR），对于PD-L1阴性肿瘤患者，为NR（95%CI，2.4-NR）。60例患者的中位无进展生存期为4.4个月（95%CI，2.1-8.3），中位总生存期为23.8个月（95%CI，14.0-NR）（65例患者中有22例（33.8%）发生任何级别的治疗相关不良事件（TRAEs），4例（6.2%）发生3-4级TRAEs。未发生与治疗相关的死亡。
GX-188E疫苗联合帕博利珠单抗用于复发性或晚期HPV阳性宫颈癌是安全的，且显示出有前景的总生存期和临床缓解率。这种联合治疗可能为复发性或晚期宫颈癌患者提供一种新的潜在治疗选择。
韩国国家癌症中心肿瘤创新部门。
