542P Ezabenlimab (BI 754091) monotherapy in patients (pts) with advanced solid tumours

Abstract

Background: Ezabenlimab is a PD-1-targeting monoclonal antibody. Ezabenlimab is being investigated as monotherapy and in combination with other anti-cancer agents, and has been administered to >600 pts in combination settings. Here, we report results in pts who received 240 mg ezabenlimab monotherapy every 3 weeks (q3w).Methods: Data from two phase I dose escalation/expansion trials and a phase I imaging trial are presented. Dose escalation cohorts enrolled pts with any advanced solid tumours. Dose expansion included pts with: select advanced solid tumours (including NSCLC, bladder, melanoma, gastric, ovarian, triple-negative breast cancer and RCC); TMB-high tumours (excluding MSI-high); squamous cell cervical/anal/skin tumours and vaginal or vulvar squamous cell carcinoma. Prior anti-PD-1 therapy was permitted in dose escalation but not in expansion cohorts. Tumour response was evaluated as per RECIST 1.1. Safety was assessed by incidence and severity of adverse events (AEs).Results: 111 pts received ezabenlimab 240 mg q3w. 83 pts (75%) were female; median age, 62 yrs. At data cut-off (Nov 2020), 13 pts remain on treatment. Best overall confirmed response is shown in the table. Duration of response ranged from 43 to 570 days (response was ongoing in 9/16 pts at data cut-off). The most common AEs (all/G3) were fatigue (38.7%/3.6%), nausea (28.8%/0) and anaemia (21.6%/10.8%). The most common drug-related AE (all/G3) was fatigue (18.0%/0). 33 pts (29.7%) had immune-related AEs, most commonly hypothyroidism (7 pts [6.3%]). 38 pts (34.2%) had serious AEs (2 were considered treatment-related [G2 pyrexia and G3 rash]). There were no AEs leading to death. 2 pts had AEs leading to discontinuation (G2 colitis and G3 musculoskeletal pain). Anti-drug antibodies occurred infrequently and did not affect the PK profile of ezabenlimab.Conclusions: Ezabenlimab monotherapy showed anti-tumour activity similar to other checkpoint inhibitors and was well tolerated.

Two phase I studies of BI 836880, a vascular endothelial growth factor/angiopoietin-2 inhibitor, administered once every 3 weeks or once weekly in patients with advanced solid tumors

“…Ongoing studies will examine the safety and antitumor activity of BI 836880 and other anticancer agents given in combination with the PD-1 inhibitor ezabenlimab in advanced solid tumors (NCT03468426 and NCT03697304). 26 , 27 , 28 , 29 , 30 As ezabenlimab is given in a Q3W schedule, and the QW schedule of BI 836880 provided no advantage over the Q3W schedule in terms of target engagement in the current studies, BI 836880 Q3W will be investigated. Based on overall assessment of efficacy, safety, and PK/PD from the current studies, the following doses were selected for the dose-finding phase of the combination study: 360, 500, and 720 mg Q3W.…”

Phase II INTERACT-ION study: ezabenlimab (BI 754091) and mDCF (docetaxel, cisplatin, and 5-fluorouracil) followed by chemoradiotherapy in patients with Stage III squamous cell anal carcinoma

“…Ezabenlimab (BI 754091), an anti-PD-1 antibody, has been investigated as monotherapy and is currently being investigated in combination with other anti-cancer therapies. The recommended Phase II dose has been determined as 240 mg given intravenously every 3 weeks and data from early phase trials suggest that the efficacy and safety profile of ezabenlimab is consistent with that of other anti-PD-1 or anti-programmed death-ligand 1 (PD-L1) antibodies ( 21 ).…”