Swedish pharmaceutical company Medivir has started patient enrolment in a Phase I/II clinical trial of its product candidate birinapant in combination with Merck’s anti-PD-1 therapy Keytruda (pembrolizumab) for treatment-refractory solid tumours.
Designed for parenteral administration, birinapant is a bivalent peptidomimetic of the second mitochondria-derived activator of caspases (SMAC) protein that binds to and degrades inhibitors of apoptosis proteins (IAPs).
The multi-centre, single arm, open-label, two-part Phase I/II trial is designed to assess the safety, tolerability and preliminary efficacy of the combination therapy, initially in the US.
Medivir chief medical officer John Öhd said: “The approval of immune checkpoint inhibitors constituted a remarkable leap forward for many cancer patients, but there still remains a substantial opportunity to improve outcomes.
“Recent preclinical data has provided a strong scientific rationale for combining birinapant with immune checkpoint inhibitors such as Keytruda.”
The Phase I dose escalation part of the trial will involve administration of increasing doses of birinapant in combination with Keytruda’s approved dose in around six subjects to determine the recommended Phase II dose of birinapant.
To be conducted in multiple patient cohorts, the subsequent Phase II part will evaluate the safety and tolerability of the combination as the primary objective, while the main secondary objective is its preliminary efficacy.
In the Phase II part, each cohort will involve subjects with the same treatment-refractory tumour type.
Birinapant is claimed to possess the potential to improve cancer treatment when given in combination with other drugs such as checkpoint inhibitors and DNA-damaging agents.