Date: 2016-11-10
Type of information: Clinical research agreement
Compound: GX-188E and Keytruda® (pembrolizumab)
Company: Genexine (Republic of Korea) Merck&Co (USA - NJ)
Therapeutic area: Cancer - Oncology
Type agreement: clinical research
Action mechanism: therapeutic vaccine/immunotherapy product/monoclonal antibody/immune checkpoint inhibitor. GX-188E is a HPV therapeutic DNA vaccine for cervical intraepithelial neoplasia (CIN) and HPV-induced cancers caused by persistent infection by high-risk HPV types, 16/18. A Phase I study demonstrated that GX-188E elicited significant E6/E7 specific IFN-?-producing T-cell responses in all CIN3 patients when administered intramuscularly by electroporation. Seven out of nine patients had complete regression of their CIN3 lesions, viral clearance, and exhibited enhanced antigen-specific polyfunctional CD8 T-cell responses within 36 weeks of follow-up. These results were published in October 2014 in Nature Communications. GX-188E is currently being developed in Phase 2 clinical trials (NCT02411019 and NCT02596243) Keytruda® (pembrolizumab - MK-3475) is a monoclonal anti-PD-1 antibody designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, pembrolizumab enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system. The pre-clinical and clinical evidence to date has suggested that IMP321 can treat cancer by activating Antigen Presenting Cells (APC) to sustain an anti-cancer immune response. This is a markedly different mechanism of action from the checkpoint inhibitors and suggests that the two approaches can be used synergistically in combination.
Disease: HPV-induced cancers
Details: * On November 10, 2016, Genexine announced that it has entered into a clinical research collaboration with Merck&Co for the assessment of Genexine’s GX-188E, HPV therapeutic DNA vaccine, in combination with MSD’s anti-PD-1 therapy, Keytruda® (pembrolizumab), for the treatment of patients with HPV-induced cancers. Under the terms of the agreement between Genexine and Merck&Co, Genexine will conduct a Phase 1b/2a clinical trial to access safety and efficacy of the combination therapy, and Merck&Co will provide clinical supplies of Keytruda® and offer support to the study. The agreement also includes provision for potential expansion to include Phase III registration studies in the same indication. Additional details were not disclosed. The purpose of the study is to investigate which combination modalities of treatment will work best in patients with advanced HPV-induced cervical cancer. An objective response rate (ORR) of 12.5% was observed in a Keytruda® clinical trial in patients with advanced cervical squamous cell cancer. Genexine expects that Keytruda is well suited to complement its HPV therapeutic DNA vaccine and that the combination with GX-188E can increase those response rates. Gleaning from the trial in CIN, the Phase 1b/2a cancer study is scheduled to begin in the first half of 2017 with plans to enroll up to 40 patients. GX-188E induces T cells specific to E6/E7 protein originated from HPV type 16 and 18 and preclinical results for the combination therapy show the potential that the induced disease-specific T cells will work synergistically with anti-PD1 Ab. The combination trial with Keytruda® and GX-188E will test to replicate animal POC in human to increase T cell specific immunotherapy.
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