Genexine , a publicly traded, clinical-stage Korean biopharmaceutical company committed to the discovery and development of novel biologics for the treatment of unmet medical needs, recently announced that GX-188E, its first-in-class proprietary DNA vaccine, demonstrated potent efficacy and favorable safety in patients with advanced cervical cancer in a phase 2 study when given in combination with KEYTRUDA (pembrolizumab), MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy.
As per the source, a total of 60 patients with HPV 16- and/or 18- positive advanced cervical cancer were analyzed in the phase 2 treatment group. Top line results showed a Best Overall Response Rate (BORR) of 31.7% (19 of 60 patients). 6 patients (10.0%) had a complete response and 13 patients (21.7%) had a partial response. Median duration of response (DOR) was 12.3 months and overall survival (OS) was 17.2 months.
The BORR increased to 38.5% in PD-L1 positive patients with HPV 16+ and Squamous Cell Carcinoma. Importantly, PD-L1 negative patients showed an ORR of 25.0%, which is extremely encouraging for this patient population, as it demonstrates potential improvement in efficacy compared to monotherapy of immune checkpoint inhibitors, suggesting a beneficial effect of the combination therapy.
In the safety analysis (n=65) 22 of 65 patients (33.8%) had treatment-related adverse events (TRAEs) of any grade and three (4.6%) had grade 3 or 4 TRAEs. The combination therapy was found to be safe and tolerable with a similar safety profile to that of pembrolizumab monotherapy.
“There is an urgent need for better therapies for patients with advanced cervical cancer and the combination of a therapeutic DNA vaccine together with checkpoint inhibition could be a strong alternative,” said professor Sung-Jong Lee of the Catholic University of Korea, College of Medicine and Investigator in the trial. “The data are very encouraging and appear to show a clear efficacy signal and the product appears safe and well tolerated. I am particularly pleased to see a clear efficacy signal in all patients, regardless of PD-L1 expression. Genexine’s combination therapy has strong appeal from a mechanistic perspective. This approach of using checkpoint inhibition to restore immune system function combined with the vaccine’s effect of upregulating and increasing the influx of CD8+ and other immune cells into the tumor microenvironment, appears to result in a strong, beneficial effect as demonstrated by major outcome measures such as BORR (31.7%) and OS (17.2 months) through the elimination of tumor cells and tumors.”
“We are very pleased to have been invited to present our phase 2 top-line data at ESMO and encouraged by the efficacy and safety shown in this study,” said Neil Warma, President and CEO of Genexine. “The combination of GX-188E, our unique DNA vaccine, with pembrolizumab could represent a new standard of care for patients with HPV 16/18 related recurrent or metastatic cervical cancer, regardless of PD-L1 expression. We are encouraged by the ORR of over 31% but particularly excited by the efficacy signal observed in PD-L1 negative patients. This could open the door to a new therapy for this patient population that previously had limited treatment options available.”
The clinical trial was an open-label, single-arm, phase 2 trial conducted in South Korea in patients with HPV-16 or HPV-18 positive advanced cervical cancer, and who had progressed after standard-of-care therapy. 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 version 1.1.
