GX-188E DNA vaccine plus pembrolizumab in HPV 16- and/or 18-positive recurrent or advance cervical cancer: a phase 2 trial

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.