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

Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: National Cancer Center Onco-Innovation Unit, Korea.