Medivir announced the first patient has been enrolled in the company's phase I/II study of birinapant in combination with the anti-PD-1 therapy KEYTRUDA (pembrolizumab), which is marketed by MSD. The objectives of the study are to evaluate the safety, tolerability and preliminary efficacy of this combination in 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. This is to be achieved by administering increasing doses of birinapant in combination with the approved dose of KEYTRUDA to cohorts of up to 6 patients with refractory solid tumors.
Once the recommended phase II dose has been identified, the second part of the study will begin. The primary objective of the phase II part is to evaluate the safety and tolerability of birinapant in combination with KEYTRUDA in several cohorts. Each cohort will be made up of patients with the same treatment refractory tumor type. An important secondary objective in the phase II part is the preliminary evaluation of the efficacy of the combination in each of the cohorts.
Under the terms of the agreement between Medivir and MSD, MSD will provide KEYTRUDA for this study at no cost to Medivir. Medivir retains full rights to birinapant. Additional details were not disclosed.
"The approval of immune check-point inhibitors constituted a remarkable leap forward for many cancer patients, but there still remains a substantial opportunity to improve outcomes. Recent preclinical data have provided a strong scientific rationale for combining birinapant with immune checkpoint inhibitors such as KEYTRUDA,” said John Öhd, Chief Medical Officer at Medivir. “We are therefore very pleased to enrol the first patient in this combination study, which will allow us to determine its safety and tolerability, as well as its potential efficacy, in patients with solid tumors who have no further treatment options."
Birinapant is a parenterally administered bivalent peptidomimetic of the SMAC protein (Second Mitochondria-derived Activator of Caspases) and is therefore known as a SMAC mimetic compound. Birinapant binds to and degrades Inhibitors of Apoptosis Proteins (IAPs), which both enables apoptosis (programmed cell death) in tumor cells, and activates the immune system, enhancing its attack on the tumor. Birinapant has the potential, through its actions on tumor cells and cells of the immune system, to improve the treatment of several types of cancer when used in combination with other drugs including checkpoint inhibitors and DNA damaging agents.