Through the early-stage trial called DUET-3, Xencor will assess the safety and tolerability of XmAb23104 in an estimated 144 patients with selected advanced solid tumors.
The participants will be subjected to intravenous administration of the investigational drug. The advanced solid tumors for which XmAb23104 will be evaluated are melanoma, cervical carcinoma, pancreatic carcinoma, breast carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, hepatocellular carcinoma and others.
DUET-3 is a multiple-dose, dose-escalation study is also aimed at characterizing the pharmacokinetics, pharmacodynamics, immunogenicity and preliminary anti-tumor activity of XmAb23104.
The bispecific antibody is said to be capable of simultaneously targeting the immune receptors PD-1 and ICOS, and is designed to promote tumor-selective T-cell activation.
According to Xencor, its XmAb bispecific Fc domain serves as the scaffold for the two antigen binding domains. The XmAb bispecific Fc domain is said to have been engineered to prevent Fc gamma receptor (FcγR) binding, with the objective to block activation and/or depletion of T cells through engagement by FcγR-expressing cells.
Xencor senior vice president and chief medical officer Paul Foster said: “We designed XmAb23104 to improve anti-tumor responses through a novel mechanism of action that activates and induces proliferation of T cells through simultaneous checkpoint inhibition and co-stimulation.
“Both PD-1 and ICOS are more highly expressed on T cells in the tumor microenvironment than on those in the periphery, and through preferential targeting of cells that express both of these receptors, we hope to be able to drive a stronger anti-tumor response than anti-PD-1 monotherapy with improved tolerability for patients.”
Based in California, Xencor is a clinical-stage biopharma company focused on developing modified monoclonal antibodies for the treatment of cancer, autoimmune diseases, asthma and allergic diseases. Till date, 13 monoclonal antibodies, which have been engineered with the XmAb technology, are in clinical development stage internally and with partners.
The XmAb antibody engineering technology is said to enable minor changes to the structure of monoclonal antibodies in order to create new mechanisms of therapeutic action.