Efficacy and safety results of GX-188E, a therapeutic DNA vaccine, combined with pembrolizumab administration in patients with HPV 16- and/or 18- positive advanced cervical cancer: Phase II interim analysis results (KEYNOTE-567).
Authors: Park Jong Sup , Hur Soo-Young , Lim Myong Cheol , Kim Yong Man , No Jae Hong , Kim Byoung-Gie , Cho Chi Heum , Kim Sung Hoon , Jeong Dae Hoon , Lee Jae-Kwan , Kim Kyungun , Choi Yoon-Jeong , Suh You Suk , Woo Jung Won , Sung Young Chul 
Published: June 2021

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Background: Pembrolizumab was approved for the treatment of recurrent or metastatic cervical cancer, based on 14.3% of objective response rate (ORR) in patients with PD-L1 expression (CPS≥1). GX-188E vaccination has been shown to induce human papillomavirus (HPV) E6- and E7-specific T-cell responses. We aimed to investigate whether a combination of GX-188E (Tirvalimogene teraplasmid) therapeutic DNA vaccine plus pembrolizumab showed antitumor activity against recurrent or advanced cervical cancer. Methods: In this open-label, single-arm, phase 2 trial, patients with recurrent or advanced cervical cancer, who were aged over 18 years with ECOG PS of 0 or 1, HPV-16 or HPV-18 and histologically confirmed positive cervical cancer, and who had progressed after standard-of-care therapy were recruited from nine hospitals 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 the Best Overall Response Rate assessed by the investigator using RECIST version 1.1. Results: To date, a total of 52 patients have been enrolled and received at least one study treatment, and this interim analysis was performed after obtaining at least one post-baseline tumor assessment data from 48 patients. Median age was 52 (range, 27-79) years and 46.2% had ECOG PS 1. At the data cutoff date on January 11, 2021, median follow-up duration was 6.2 months (range; 1.7- 24.2 months). According to investigator evaluation, 15 (31.3%) of 48 patients achieved best overall response; 5 (10.4 %) patients had a complete response (CR) and 10 (20.8 %) had a partial response (PR). Especially, this combination treatment showed higher response rate, 48.0 %, in patients with PD-L1 positive, HPV-16 and squamous cell carcinoma. Median PFS was 4.1 months (range; 1.3-24.2) and median OS was 16.7 months (range; 1.7-24.2). In this clinical trial with cervical cancer patients, GX-188E in combination with pembrolizumab has shown an improved median PFS and OS than the monotherapy of pembrolizumab (KEYNOTE-158). 17 (32.7%) of 52 patients had treatment-related adverse events of any grade and two (3.8%) had grade 3 or 4 treatment-related adverse events; increased aspartate aminotransferase or alanine aminotransferase. No treatment-related deaths were reported. Conclusions: GX-188E vaccine combined with pembrolizumab in recurrent/advanced cervical cancer was safe and tolerable, and showed an enhanced clinical response rate compared with pembrolizumab alone in particular in patients with PD-L1 positive, HPV-16 and squamous cell carcinoma. The combination therapy could represent a new potential treatment option for this patient population. Clinical trial information: NCT03444376.