Boehringer Ingelheim and OSE Immunotherapeutics SA announce that the first patient has been dosed in the expansion phase of the Phase 1 clinical trial evaluating BI 765063, a first-in-class monoclonal antibody antagonist of SIRPa, in combination with ezabenlimab, an anti-PD1 monoclonal antibody (BI 754091) in patients with microsatellite stable (MSS) advanced endometrium or colorectal cancer. Both tumors are with a high unmet medical need. BI 765063 is a first-in-class SIRPa inhibitor on the CD47/SIRPa “Don’t eat me” pathway being developed under collaborative agreement between OSE Immunotherapeutics and Boehringer Ingelheim. The dose escalation part of the Phase 1 trial (Step 1), evaluating BI 765063 alone and in combination with ezabenlimab, has been completed with a total of 18 patients enrolled in combination. Patients with advanced solid tumours and who failed or were not eligible for standard therapy were enrolled from two prespecified groups: (1) patients who are genetically SIRPa homozygous (V1/V1) or (2) heterozygous (V1/V2). Two dose levels of BI 765063 (18 and 24 mg/kg IV every 3 weeks) were evaluated in combination with ezabenlimab (240 mg IV every 3 weeks). During the dose escalation, BI 765063 alone or in combination was well tolerated with no haematologic toxicity and the maximum tolerated dose (MTD) was not reached. The recommended Phase 2 dose (24 mg/kg) and optimal treatment schedule of BI 765063 was established with assays determining full receptor occupancy from cycle 1 and using a once every three week dosing schedule. In addition, promising early efficacy of BI 765063 was observed both alone and in combination, especially in advanced hepatocellular carcinoma, endometrium and colorectal cancer, including microsatellite stable (MSS) tumors. Promising early efficacy was observed with one partial response (PR) in monotherapy in a patient with advanced hepatocellular carcinoma and three partial responses in combination in patients with MSS advanced endometrium or colorectal cancer. The trial expansion aims to further assess preliminary efficacy of BI 765063 in combination with ezabenlimab in two selected tumor types of V1/V1 homogygous patients from whom a clinical benefit has been observed: MSS advanced colorectal cancer (around 30 patients) and MSS advanced endometrium cancer (around 10 patients) whose disease relapsed after standard of care and who received no prior anti-PD-L1 inhibitors. The study is being conducted by OSE Immunotherapeutics as part of a collaboration and license agreement under which Boehringer Ingelheim obtained exclusive rights to BI 765063. Under the terms of the collaboration and license agreement, dosing of the first patient in expansion of this Phase 1 trial triggers a milestone payment of €8 million to OSE Immunotherapeutics from Boehringer Ingelheim. BI 765063 is a monoclonal antibody antagonist of the key myeloid cell checkpoint inhibitor SIRPa. BI 765063 prevents the SIRPa ligand CD47, from binding to SIRPa thereby preventing cellular signalling that can reduce the anti-tumorigenic properties of myeloid cells such as macrophages and dendritic cells. In March 2019, OSE Immunotherapeutics received Clinical Trial Authorization for a Phase 1 study by two health agencies (France and Belgium) to evaluate BI 765063 in patients with advanced solid tumors. The study is conducted by OSE Immunotherapeutics as part of a collaboration and license agreement under which Boehringer Ingelheim obtained exclusive rights to BI 765063, originally signed in April 2018.