ATOR-1015: Tumor-localizing bispecific CTLA-4 antibody with dual immunostimulatory function

ATOR-1015 binds to two different immunomodulatory receptors – the CTLA-4 inhibitory receptor, and an OX40 costimulatory receptor. In preclinical studies, the biospecificity has been shown to cause a significant increase in the immunostimulatory effect and is expected be achieved mainly in environments where both of the target molecules are expressed at high levels, such as in a tumor. This means that ATOR-1015 may have potent immunostimulatory effects in the tumor environment, but not in the rest of the body, with the goal of reducing the side effects while maintaining efficacy.

1. ATOR-1015 binds to CTLA-4 and OX40 on the regulatory T cells, the cells which restrain the immune system.
2. The macrophages are activated to kill Tregs, removing the inhibitory effect of Tregs on the beneficial T cells.
3. The effector T cells (light green) are multiplied in number and are activated to kill the tumor cells.

Project status

The ongoing dose escalation study in patients with metastatic cancer is planned to comprise up to 53 patients. The principal investigator is Dr Jeffrey Yachnin from the Department of Oncology at Karolinska University Hospital in Stockholm. The primary endpoint of the study is to investigate the safety and tolerability of ATOR-1015 and to determine the recommended dose for subsequent Phase II studies.

The study commenced in March 2019 with a titration phase using a single patient per dose level. This phase was then followed by the standard 3+3-design, where a cohort of at least three patients per dose level are treated before escalating to a higher dose. The study is progressing well and in February 2020 evaluation of 400 mg dosing, about 6 mg/kg given every two weeks, was initiated. Current dosing has reached a level that is likely to produce both benefits and side effects.

For further information, refer to https://www.clinicaltrials.gov/ct2/show/NCT03782467?term=1015&rank=1.