LBA32 - 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

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.

Editorial acknowledgement

Legal entity responsible for the study

Genexine, Inc.

Funding

Sponsor: Genexine, Inc. Government funding: National Cancer Center Onco-Innovation Unit. Supply of pembrolizumab: Merck Sharp & Dohme, a subsidiary of Merck & Co.

Disclosure

S. Lee: Financial Interests, Institutional, Other, Sub-investigator: Catholic University of Korea, Seoul St. Mary's Hospital. M. Lim: Financial Interests, Institutional, Principal Investigator: National Cancer Center. Y.M. Kim: Financial Interests, Institutional, Principal Investigator: Asan Medical Center. J.H. No: Financial Interests, Institutional, Principal Investigator: Seoul National University Bundang Hospital. B. Kim: Financial Interests, Institutional, Principal Investigator: Samsung Medical Center. C.H. Cho: Financial Interests, Institutional, Principal Investigator: Keimyung University Dongsan Medical Center. S.H. kim: Financial Interests, Institutional, Principal Investigator: Yonsei University College of Medicine. D.H. Jeong: Financial Interests, Institutional, Principal Investigator: Inje University Busan Paik Hospital. J. lee: Financial Interests, Institutional, Principal Investigator: Korea University Guro Hospital. J.S. Park: Non-Financial Interests, Institutional, Full or part-time Employment: Genexine, Inc.; Financial Interests, Institutional, Sponsor/Funding, Genexine, Inc.: Genexine, Inc.; Financial Interests, Institutional, Stocks/Shares: Genexine, Inc.. Y. Choi: Non-Financial Interests, Institutional, Full or part-time Employment: Genexine, Inc.; Financial Interests, Institutional, Project Lead: Genexine, Inc.; Financial Interests, Institutional, Sponsor/Funding: Genexine, Inc.. K.O. Jeon: Non-Financial Interests, Institutional, Full or part-time Employment: Genexine, Inc.; Financial Interests, Institutional, Sponsor/Funding: Genexine, Inc.. J.W. Woo: Non-Financial Interests, Institutional, Member of the Board of Directors: Genexine, Inc.; Financial Interests, Institutional, Stocks/Shares, Genexine, Inc.: Genexine, Inc.; Financial Interests, Institutional, Sponsor/Funding: Genexine, Inc.. Y.C. Sung: Non-Financial Interests, Institutional, Advisory Board: Genexine, Inc.; Financial Interests, Institutional, Stocks/Shares: Genexine, Inc.. S. Hur: Financial Interests, Institutional, Principal Investigator: Catholic University of Korea, Seoul St. Mary's Hospital.