As reported in The Lancet Oncology by Youn et al, interim results of a Korean phase II trial indicated activity with the combination of pembrolizumab plus the therapeutic DNA vaccine GX-188E in patients with human papillomavirus (HPV)-16– or HPV-18–positive advanced cervical cancer.

GX-188E (tirvalimogene teraplasmid) is a therapeutic HPV DNA vaccine that encodes HPV-16 and HPV-18 E6 and E7.

As stated by the investigators, “Pembrolizumab has been approved for the treatment of recurrent or metastatic cervical cancer, with an overall response rate of 14.3%. GX-188E vaccination has been shown to induce HPV E6-specific and E7-specific T-cell responses and cervical lesion regression in patients with cervical precancer.”

Study Details

The multicenter trial enrolled 36 patients with recurrent or advanced HPV-16– or HPV-18–positive cervical cancer who had disease progression after available standard-of-care therapy between June 2018 and March 2020. Treatment consisted of intramuscular GX-188E at 2 mg at weeks 1, 2, 4, 7, 13, and 19 (with one optional dose at week 46 at investigator discretion), and pembrolizumab at 200 mg every 3 weeks for up to 2 years or until disease progression. The primary endpoint was investigator-assessed overall response rate within 24 weeks using Response Evaluation Criteria in Solid Tumors version 1.1 in patients who received at least 45 days of treatment with at least one postbaseline tumor assessment.

Responses

Among a total of 26 patients evaluable for interim activity, 11 (42%) had an objective response at 24 weeks, including complete response in 4 (15%). An additional four patients (15%) had stable disease, yielding a disease control rate of 58%. Response was observed in 10 (50%) of 20 patients with PD-L1–positive disease (combined positive core > 1), 1 (17%) of 6 with PD-L1–negative disease, 9 (45%) of 20 with HPV-16–positive disease and 2 (33%) of 6 with HPV-18–positive disease.

All patients with a complete response had ongoing responses at data cutoff, with durations ranging from 3.3 months to 13.6 months. Responses were ongoing at data cutoff in six of seven patients with partial response, with durations ranging from 1.3 months to 7.7 months. Among the 26 patients, median progression-free survival was 4.9 months (95% confidence interval = 2.1–6.7 months), with a 6-month rate of 35%. DNA vaccine–induced T-cell responses were observed in 18 (78%) of 23 response-evaluable patients.

Toxicity

Treatment-related adverse events of any grade occurred in 16 (44%) of 36 patients. Grade 3 or 4 treatment-related adverse events occurred in four patients (11%) and consisted of grade 3 increased aspartate aminotransferase, syncope, pericardial effusion, and hyperkalemia, and grade 4 increased alanine aminotransferase. Drug-related serious adverse events included one case of grade 3 pericardial effusion and one case of grade 2 pyrexia. Immune-related adverse events occurred in seven patients (19%; all grade 1 or 2), with the most common being hypothyroidism (4 patients, 11%). No treatment-related deaths were reported.

The investigators concluded, “Treatment with GX-188E therapeutic vaccine plus pembrolizumab for patients with recurrent or advanced cervical cancer was safe and treatment-related adverse events were manageable. This combination therapy showed preliminary antitumor activity in this interim analysis, which could represent a new potential treatment option for this patient population. This trial is ongoing.”

Young Chul Sung, PhD, of Genexine, Seongnam-si, South Korea, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by National OncoVenture. For full disclosures of the study authors, visit thelancet.com.