An open-label, phase Ib trial of the SIRPα inhibitor BI 765063 in combination with the PD-1 inhibitor ezabenlimab and cetuximab in patients (pts) with head and neck squamous cell carcinoma.

Abstract

6019 Background: BI 765063 is a first-in-class, humanized IgG4 monoclonal antibody that binds the V1 allele of signal regulatory protein α (SIRPα) and blocks the ‘don’t eat me’ signal of the SIRPα/CD47 axis. This leads to reactivation of innate antitumor responses, restoring phagocytosis and antigen presentation. In a Phase Ia/Ib trial in pts with advanced solid tumors (NCT03990233), BI 765063 ± ezabenlimab was well tolerated with no dose-limiting toxicities and preliminary efficacy was observed (Kotecki et al, ESMO 2021). This Phase Ib study (NCT05249426) is investigating the efficacy and safety of BI 765063 in combination with ezabenlimab + cetuximab (Cohort A) or ezabenlimab + chemotherapy (Cohort B) in pts with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), or in combination with ezabenlimab ± BI 836880 (anti-VEGF/Ang2) in pts with hepatocellular carcinoma. Here, we focus on pts with HNSCC who received BI 765063 combined with ezabenlimab + cetuximab (Cohort A). Methods: In Cohort A, adult pts with R/M HNSCC who had received 1 previous systemic therapy (excluding immune checkpoint inhibitors) were eligible. Other inclusion criteria included SIRPα V1/V1 homozygosity (detected in plasma), ≥1 measurable lesion (RECIST v1.1) and ECOG performance status of 0/1. Pts received BI 765063 (24 mg/kg every 3 weeks [q3w]), ezabenlimab (240 mg q3w) and cetuximab (per local guidelines). Primary endpoint was confirmed objective response (OR; RECIST v1.1). Secondary endpoints included disease control (DC) and treatment-emergent adverse events (TEAEs). Results: At data cut-off (Dec 2, 2024), 18 pts had been enrolled to Cohort A and received BI 765063 plus ezabenlimab + cetuximab (1 pt was subsequently found to be ineligible). Of the 17 eligible pts, median age was 51 years (range, 33–81), 88% were male and all had received 1 prior therapy. Eight pts (47%) achieved a confirmed OR (3 complete and 5 partial responses) and a further 7 (41%) achieved stable disease to give a DC rate of 88%. Median duration of DC was 7.6 months. TEAEs were reported in all 17 pts. Most common TEAEs were acneiform dermatitis (any grade/grade ≥3, 53%/0%), anemia (35%/24%), hypokalemia (29%/6%), hypothyroidism (29%/0%) and rash (29%/0%). Most common BI 765063 treatment-related AEs (TRAEs) were hypothyroidism (24%) and acneiform dermatitis (18%), all grade 1/2. Grade 3 TRAEs (asthenia, cardiac failure, epistaxis, hypoalbuminemia, lymphopenia, mouth hemorrhage, post-procedural hemorrhage and suspected drug-induced liver injury) were each reported in 1 pt. There were no grade 4/5 TRAEs. Conclusions: These preliminary data indicate that BI 765063 in combination with ezabenlimab and cetuximab has a manageable safety profile and promising efficacy as second-line treatment in pts with R/M HNSCC. Biomarker data will be presented at the meeting. Clinical trial information: NCT05249426 .