ADU-1604 is a humanized IgG1 monoclonal antibody in development for use as monotherapy or in combination with other anti-cancer therapies. It targets a novel epitope on the validated inhibitory receptor, CTLA-4. ADU-1604 was characterized in vitro and shown to bind to human CTLA-4, block binding of CD80 and CD86 to CTLA-4, and stimulate IL-2 production by activated lymphocytes. ADU-1604 enhanced T cell dependent hepatitis B surface antigen vaccine-induced antibody responses in cynomolgus monkeys and demonstrated anti-tumor activity in a non-small cell lung cancer patient-derived xenograft humanized mouse model. The primary objective of the first-in-human study is to determine the recommended phase 2 dose (RP2D) by evaluating the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ADU-1604 administered as an intravenous (IV) infusion.
This first-in-human, open-label, multicenter, dose-escalation study is conducted in adults with metastatic melanoma without further established treatment options. The study includes two parts: 1) Dose Escalation starts with 0.3 mg/kg of ADU-1604 IV infusion in 3-6 subjects and dosing is escalated until the RP2D is defined (represented by the dose tolerated while not exceeding the maximum tolerated dose or maximum dose (10 mg/kg)). 2) In Dose Confirmation, 7-10 additional subjects receive ADU-1604 at the RP2D until the maximum number of planned doses are administered (4 treatment cycles), disease progression is confirmed, or consent is withdrawn, whichever occurs first. The end of the study is defined as the date when all subjects have completed the final protocol-specified safety assessment and/or discontinued study participation. Primary endpoints include incidence of dose limiting toxicity, treatment-emergent adverse events (TEAEs), and changes from baseline in safety parameters. Secondary endpoints include severity of TEAEs, serious adverse events, changes from baseline in safety assessments, serum concentration-time profiles and PK parameters (including Cmax, AUC), and incidence of anti-ADU-1604 antibodies. This study is designed to provide the RP2D of ADU-1604 based on the totality of PK-PD, as well as clinical responses and safety.
NCT03674502.
Aduro Biotech Europe.
Aduro Biotech Europe.
M. Hendriks, E. de Cock, K. Maplestone, H. Namini, A. van Elsas: Employee of and holds stock in Aduro Biotech Europe at the time of this work.