Efficacy And Safety Results Of Pembrolizumab Combined With Gx-188e, A Therapeutic Dna Vaccine Administration In Patients With Hpv 16-And/Or 18-Positive Advanced Cervical Cancer: Phase Ii Interim Analysis Results

Purpose: Pembrolizumab was approved for the treatment of patients with relapsed or metastatic cervical cancer with disease progression on or after chemotherapy, whose tumors express PD-L1 (CPS≥1), with a 14.3% objective response rate (ORR) by the U.S. FDA in 2018 (KEYNOTE-158). Combination of pembrolizumab with GX-188E, a DNA vaccine targeting HPV 16 and 18 types is expected to show synergistic anti-tumor effects presumably by antigen-specific CD8+ T cell responses induced by GX-188E DNA vaccine. The objectives of this interim analysis are to assess preliminary anti-tumor efficacy, safety and tolerability. Patients and Design: This is a prospective, open-label, phase II study in patients with advanced, inoperable or metastatic cervical cancer, ECOG PS 0-1, positivity for HPV 16 and/or 18 types who have failed all available standard-of-care (SoC) therapies including surgery, chemotherapy and radiotherapy or who have refused those (≥2 lines). Patients received GX-188E 2 mg intramuscularly, seven times at weeks 1, 2, 4, 7, 13, 19, and 46, with pembrolizumab 200 mg IV every three weeks for up to 2 years or until progression. This interim analysis was performed after obtaining at least one post baseline tumor assessment data from 22 patients (approximately 50% of total patients to be enrolled in Phase II). Results: Among 24 patients treated, 22 patients were evaluable for anti-tumor efficacy. Median age was 52 (range, 27-68) years and 37.5% had ECOG PS 1. As of the Dec 11, 2019 data cutoff, the median follow-up duration was 5.3 months (range; 0.9-16.3 months). ORR was 45.5%, with 5 CRs and 5 PRs. Additionally, one patient had SD at week 14. Median PFS was 4.1 months (range; 1.7-not reached). Median DoR and OS have not been reached. Treatment related AEs occurred in 54.2% of patients with grade 1 or 2 and 12.5% of patients with grade 3-4. The most common treatment related AEs classified by system organ class were gastrointestinal disorders (20.8%) and respiratory, thoracic and mediastinal disorders (16.7%), which were similar to those of pembrolizumab monotherapy. In contrast to pembrolizumab monotherapy, combined therapy showed therapeutic effect in PD-L1 negative tumor. Conclusions: Pembrolizumab combined with GX-188E demonstrated a higher response rate than pembrolizumab monotherapy in patients with cervical cancer showing great synergy regardless of PD-L1 expression. The safety profile was manageable and similar to that of pembrolizumab monotherapy. Further evaluation of anti-tumor response and antigen specific immune response is ongoing in a larger number of patients with and without PD-L1 expression. Citation Format: Sooyoung Hur, Jong Sup Park, Yong-Man Kim, Myong Cheol Lim, Jae Hong No, Byoung-Gie Kim, Jae-Kwan Lee, Chi Heum Cho, Yoon-Jeong Choi, You Suk Suh, Jung Won Woo, Young Chul Sung. Efficacy and safety results of pembrolizumab combined with GX-188E, a therapeutic DNA vaccine administration in patients with HPV 16- and/or 18- positive advanced cervical cancer: Phase II interim analysis results [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT033.