Despite recent breakthroughs with immuno-oncology agents in cancer treatment, patients with certain types of solid tumors have few or no options and are in need of treatments to extend life. These patients have significant unmet medical needs.
Birinapant is being developed to enhance responses, and extend survival, of patients with solid tumors where existing treatments do not provide sufficient survival benefit, or where patients no longer have treatment options. Based on its unique design and mechanism, birinapant has the potential to enhance patients’ responses in combination with other treatments. Medivir’s initial focus is on developing birinapant in combination with an immuno-oncology agent.
Birinapant is a highly potent molecule that binds to and degrades cellular Inhibitor of Apoptosis Proteins (cIAPs), causing their degradation. Degradation of the cIAPs enables cell death in tumor cells, and augments the immune system response, enhancing its attack on the tumor. Through its actions on tumor cells and cells of the immune system, birinapant has the potential to improve the treatment of several types of cancer when used in combination with other drugs, including checkpoint inhibitors and DNA damaging agents.
In August 2017, Medivir initiated a clinical phase I/II study of birinapant in combination with Keytruda®, to clinically demonstrate birinapant’s effect as a combination treatment for patients with treatment-resistant solid tumors.
The multicenter, single arm, open label study, which is primarily being run in the US, will be conducted in two parts. In the initial dose escalation (phase I) part of the study, the objective is to identify the recommended phase II dose of birinapant for use in combination with Keytruda®. The second part of the study will evaluate the preliminary efficacy as well as the safety and tolerability of birinapant in combination with Keytruda® in several cohorts.
Medivir has an agreement with Merck & Co. under which Merck provides Keytruda® for this trial at no cost to Medivir and participates on a Joint Development Committee bringing their considerable immuno-oncology expertise. Medivir retains all rights to birinapant as well as the data generated. It is likely that after demonstrating clinical efficacy, Medivir would out-license birinapant to a partner with global development and commercialization capabilities within oncology, potentially prior to phase III. In order for birinapant to be further developed in combination with an immunotherapy-based treatment, a partner owning the rights to such treatments would be desirable.
Unmet medical need
To enhance responses, and extend survival, of patients with solid tumors.
Birinapant is a SMAC mimetic. Preclinical studies have established its potential to be combined with immunooncology drugs, and other classes of cancer drugs, to enhance responses in patients.
Start expansion studies, (phase II) portion of the phase I/II trial, once dose has been selected in dose-escalation part (phase I).