Under the terms of the agreement, Genexine will conduct a Phase 1b/2a study to evaluate the effectiveness and safety of the combo treatment, while Merck will offer support to the trial and provide supplies of Keytruda, according to a press release.
The contract also includes pre-arrangements for a potential expansion to include Phase 3 registration clinical trials in HPV-induced cancers testing the same combination.
GX-188E is a therapeutic DNA vaccine encoding the fusion protein of human papillomavirus (HPV) subtypes 16 and 18 with an immune-enhancer. This fusion protein induces T-cells to recognize and kill HPV-positive tumor cells.
Keytruda blocks the interaction between the PD-1 receptor found on the surface of T-cells and its ligands PD-L1 and PD-L2, allowing for a proper T-cell activation and tumor targeting.
Preclinical data for the combination treatment suggests the induced disease-specific T-cells could work synergistically with anti-PD1 antibodies.
The clinical trial of the Keytruda and GX-188E combination seeks to reproduce these proof-of-concept studies in humans to increase T-cell specific immunotherapy.
The trial will evaluate which treatment combinations are more clinically beneficial for patients with advanced HPV-induced cervical cancer. In patients with advanced cervical squamous cell cancer, treatment with Keytruda resulted in an objective response rate of 12.5%.
Genexine anticipates that Keytruda will be a good immunotherapeutic agent to complement its GC-188E DNA vaccine, and that the combination will increase response rates.
Enrollment in the Phase1b/2a clinical trial should begin by mid-2017, with 40 patients expected to participate.
GX-188E’s safety, effectiveness, and maximum tolerated dose are currently being evaluated in four Phase 2 clinical trials (NCT02411019, NCT02100085, NCT02596243, NCT02139267) in specific patients with a diagnosis of HPV-positive cervical intraepithelial neoplasia (CIN) 2, 2/3 or 3.
In a Phase 1 clinical trial (NCT01634503), GX-188E caused significant E6/E7 specific interferon-gamma-producing T-cell responses in all CIN3 patients. At 36 weeks of follow-up, of the nine patients treated, seven achieved complete regressions of their lesions.