A phase 1/2 study with birinapant in combination with pembrolizumab.

TPS3131Background: Birinapant is a bivalent SMAC mimetic with activity against multiple members of the inhibitor of apoptosis protein (IAP) family including cIAP1 and has demonstrated tolerability with robust and durable target engagement in advanced cancers. Synergistic effects of combining birinapant with immune checkpoint inhibitors have been demonstrated in preclinical models, consistent with the reported role of cIAP1 in tumor cells and immune cells (Beug et al., 2017). Based on these observations, a phase 1/2 trial with birinapant and pembrolizumab has been initiated (NCT02587962). Methods: In the dose escalation part of this multi-center phase 1/2 study, patients > 18 years with advanced solid tumors without further suitable standard therapeutic options are eligible for inclusion. The primary objective is to determine the safety and tolerability of the recommended phase 2 dose (RP2D) of birinapant in combination with pembrolizumab using a standard 3+3 design. The secondary objective is to assess ef...