Genexine said its investigational DNA vaccine for cervical cancer has improved the response rate of immunotherapy Keytruda significantly.
The company released interim results of the local phase-1b/2 clinical trial on the combined therapy of GX-188E and MSD’s immunotherapy Keytruda (ingredient: pembrolizumab) at the online meeting of the American Association for Cancer Research (AACR) on Monday.
Genexine Vice President Woo Jung-won made an oral presentation of the interim results at the AACR’s plenary session.
Genexine’s trial evaluates the safety and efficacy of the combination therapy of GX-188E and Keytruda in cervical cancer patients with human papillomavirus (HPV) type 16 or 18 who did not respond to the standard treatment. Patients with HPV type 16 and 18 account for 70 percent of cervical cancer patients. The company has recruited 36 patients so far and released the results on 26 patients available for analysis.
The primary endpoint is the combo treatment’s objective response rate (ORR), compared to that of Keytruda alone.
The FDA approved Keytruda as a second-line treatment for cervical cancer patients with programmed death-ligand 1 (PD-L1) expression in 2018. However, the drug’s low response rate has been cited as its limitation. The KEYNOTE-158 trial showed that Keytruda’s ORR stood at only 14.6 percent in 98 cervical cancer patients.
According to the presentation, the combo of GX-188E and Keytruda achieved a significant increase in ORR, compared to Keytruda alone. The ORR of 26 patients available for evaluation was 42.3 percent, and the disease control rate (DCR) was 57.7 percent. In particular, four patients (15.6 percent) had complete remission (CR), and seven patients (26.9 percent), partial remission (PR). Four (15.4 percent) had stable disease (SD) reaction without cancer progression, and 11 (42.3 percent), progressive disease (PD) reaction with cancer progression.
The effect of the combo was particularly noticeable in patients with PD-L1 expression. Twenty patients whose PD-L1 expression was higher than 1 percent had 50 percent ORR. Complete remission appeared only in patients with PD-L1 expression.
The combo also worked in PD-L1 negative patients who did not respond to the Keytruda monotherapy. The ORR in PD-L1 negative patients recorded 16.7 percent.
The combined therapy showed a higher response (47.4 percent ORR) in HPV type 16 patients than those with HPV type 18 (28.6 percent ORR). Eighteen of the 23 patients (78.3 percent) demonstrated an antigen-specific T cells response, proving that GX-188E effectively induced the patients’ HPV 16/18 specific immune response, the company said.
Among the 28 patients treated with the combo therapy, 10.7 percent showed severe adverse reactions of Grade 3 or higher, which was similar to the proportion (12.2 percent) of patients treated with Keytruda alone.
“The combined therapy of GX-188E and Keytruda showed a safety profile similar to monotherapy of Keytruda,” Woo said. “The therapy significantly improved patients’ response rate to 42.3 percent. By showing clinical response in PD-L1 negative patients, too, the combined therapy proved its safety and effectiveness.”
Nina Bhardwaj, a professor of medicine and urology at Icahn School of Medicine at Mount Sinai, who led a debate at the conference, said that although there were some things to consider such as identifying biomarkers for responses and resistance to immunotherapy combinations, the combo therapy of GX-188E and Keytruda showed the potential of anticancer activity in both PD-L1 positive and negative patients.