ADC-1013 is a human, monospecific, agonistic, IgG1 antibody intended for immunotherapy of cancer. The drug candidate targets the co-stimulatory receptor CD40, which is expressed on, for example, antigen-presenting dendritic cells. The dendritic cells reside in blood vessels and various tissues where they discover and digest proteins from viruses, bacteria or cancer cells. Next, the digested proteins are presented to so-called T-cells which are activated and kill the infected cells or the cancer cells. ADC-1013 activates CD40 on dendritic cells, enabling them to activate T-cells more effectively and thereby increasing the immune system's attack of the cancer. This is the primary mechanism of action of this drug candidate. In addition, since some cancer cells express CD40 on the surface, ADC-1013 may also act through a secondary mechanism of action by directly killing cancer cells.
The figure illustrates the cancer immunity cycle, describing how the immune system attacks tumors. The primary mechanism of action of ADC-1013 is activation of dendritic cells by the stimulation of the co-stimulatory receptor CD40. Dendritic cells that are activated by stimulation with ADC-1013 can effectively instruct the T-cells to find and kill tumor cells in the whole body. Since some tumor cells express CD40 on the surface, ADC-1013 may also act through a secondary mechanism of action by directly killing such tumor cells.
Preclinical studies indicate that agonistic CD40 antibody therapy can be used for treatment of several tumor types such as lymphoma, melanoma, hepatocellular carcinoma, osteosarcoma, renal cell carcinoma, breast cancer, colorectal cancer, lung cancer and bladder cancer.
A phase I study (ClinicalTrials.gov: NCT02379741) of ADC-1013 was initiated in April 2015 and completed in March 2017. The study is a dose-escalation study involving intratumoral and intravenous administration of ADC-1013 at five clinical sites in Sweden, Denmark and the UK (ClinicalTrials.gov: NCT02379741). The study is sponsored by Alligator and includes 24 patients and ten different tumor types. Study data will be presented in November 2017 at the scientific conference Society for Immunotherapy of Cancer 32nd Annual Meeting (SITC).
In August 2015, Alligator outlicensed the global development and commercialization rights of ADC-1013/JNJ-64457107 to Janssen Biotech Inc. In October 2016, Janssen Biotech started a second phase I clinical study (ClinicalTrials: NCT02829099). This study is ongoing and to date, approximately 50 patients have been enrolled in the study. Additional combination studies are planned.
The main goal of both phase I studies is to identify a safe, tolerable and biologically effective dose level for ADC-1013/JNJ-64457107.