The results were presented in the “Clinical Plenary: Immunotherapy Clinical Trials 1” session of AACR 2020
During the AACR Annual Meeting 2020, in one of the first plenary sessions held this Monday, April 27th, an interesting study presented by Dr. Jung Won demonstrated that the combination of pembrolizumab with GX-188E proved to be effective and safe in the treatment of patients with metastatic or refractory cervical cancer caused by HPV types 16 and 18, after failure of two or more previous standard therapies.
GX-188E is a DNA vaccine designed to preferentially induce CD8 + T cell responses directed to HPV antigens types 16 and 18, which are responsible for 70% of cervical cancer cases.
Pembrolizumab monotherapy demonstrated a response rate of 14.6% in positive PD-L1 patients. The presented phase 2 study recruited 36 patients, who were treated with GX-188E at a dose of 2mg intramuscularly at weeks 1, 2, 4, 7, 13 and 19 (optional at week 46) and 200mg intravenous pembrolizumab every 3 weeks for up to 2 years or until progression.
The interim analysis showed that 53.6% of the patients had adverse events (AEs) of any degree and 10.7% of grades 3 and 4. As a comparison, pembrolizumab monotherapy had AEs of any degree in 65.3% of the patients and grades 3 and 4 by 12.2% on Keynote-158. There was no treatment-related death.
Efficacy was assessed in 26 patients, who received at least 45 days of treatment. The overall response rate was 42.3%, with 4 complete and lasting responses, and 7 partial responses. The response was higher in PD-L1 positive than negative patients (50% versus 28.6%, respectively) and with HPV-16 compared to HPV-18 (47.4% versus 28.6%, respectively).
Initial responses began to be seen from week 10 and became more intense over time. The current median progression-free survival is 5 months (range from 2.1 to not achieved) and the median follow-up is 6.3 months.
The study also analyzed the antigen-specific response of T cells, which was present in 78.3% of the patients, demonstrating the effectiveness of GX-188E in inducing the specific immune response. All patients with partial or complete response had an immune response associated with the clinical response.
The combined treatment of pembrolizumab and GX-188E was safe and well tolerated, it demonstrated a higher response rate (42.6%) compared to monotherapy with pembrolizumab, and it induced a specific immune response.