Efficacy and safety of GX-188E, a therapeutic DNA vaccine, combined with pembrolizumab in HPV 16-and/or 18-positive advanced cervical cancer (phase II): Safe and effective in both PD-L1 positive and negative

Abstract

Background GX-188E (tirvalimogene teraplasmid) is a therapeutic DNA vaccine that encodes HPV-16 and HPV-18 E6 and E7 and induces HPV-specific T-cell responses. Pembrolizumab was approved for the treatment of advanced cervical cancer, based on an objective response rate (ORR) of 14.3% in patients with PD-L1 positive (CPS≥1). However, patients who were PD-L1 negative (CPS<1) showed no response to treatment with pembrolizumab. We aimed to investigate whether a combination of GX-188E plus pembrolizumab showed antitumor activity against advanced cervical cancer regardless of PD-L1 expression.

Methods In this open-label, single-arm, phase 2 trial, patients with HPV-16 or HPV-18 positive advanced cervical cancer, and who had progressed after standard-of-care therapy were recruited 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 ORR assessed by the blinded independent central reviewers (BICR) using RECIST v1.1.

Results A total of 65 patients have been enrolled and 60 patients were analyzed as efficacy population based on having at least one post-baseline tumor assessment. Among 60 patients, 36 patients had PD-L1 positive tumors and 24 patients were PD-L1 negative. According to BICR evaluation, 19 of 60 patients (31.7%) achieved best overall response; 6 patients had a complete response and 13 patients had a partial response. Especially, in PD-L1 negative population with 24 patients, this combination treatment showed significant efficacy (25.0% ORR). Median DOR was 12.3 months and median OS was 17.2 months. 22 of 65 patients (33.8%) had treatment-related adverse events (TRAEs) of any grade with three patients (4.6%) presenting with grade 3 or 4 TRAEs.

Conclusions GX-188E vaccine combined with pembrolizumab in advanced cervical cancer was safe and tolerable, and showed significant efficacy compared with pembrolizumab alone particularly in patients with PD-L1 negative. This combination therapy could represent a new potential treatment for this patient population.

Clinical trial identification NCT03444376