Phase 1 study of OX40 agonist ABBV-368 as monotherapy or in combination with budigalimab in advanced solid tumors

AIMS: This first-in-human phase 1 trial evaluated the OX40 agonist antibody ABBV-368 as monotherapy and with the anti-programmed cell death protein (PD)-1 budigalimab in advanced solid tumors. PATIENTS AND METHODS: In dose escalation, patients with solid tumors received ABBV-368 monotherapy. In dose expansion, patients with relapsed/refractory triple-negative breast cancer (TNBC) received ABBV-368 monotherapy, and patients with anti-PD-(ligand)1-naive or relapsed/refractory head and neck squamous cell carcinoma (HNSCC) received ABBV-368 and budigalimab combination. A novel biomarker detecting active OX40 guided dose optimization. Primary objectives were safety, tolerability, and pharmacokinetics evaluation. Preliminary efficacy and biomarkers were examined. ABBV-368 exhibited dose-proportional pharmacokinetics, which were not altered by budigalimab coadministration. Treatment-related adverse events (AEs) occurred in 44% (escalation), 43% (TNBC), and 53% (HNSCC) of patients; immune-related AE rates were those expected for anti-PD-1 therapies; two patients had ABBV-368- and budigalimab-related serious AE of colitis. There were two complete and three partial confirmed responses. Biomarkers reflected CD8 T-cell activation and interferon-gamma (IFNγ)-induced activity. CONCLUSIONS: ABBV-368 with/without budigalimab was well tolerated and induced dose-specific immune cell activation in advanced solid tumors. Further combination or optimization strategies are required for meaningful clinical benefit.