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. RESULTS: = 51). 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.
Authors
- Toshihiko Doi (ORCID: https://orcid.org/0000-0003-2042-6829)
- Luija Wang
- Ki Young Chung (ORCID: https://orcid.org/0000-0001-6586-2013)
- Victor Moreno (ORCID: https://orcid.org/0000-0001-6099-4236)
- Philippe Alexandre Cassier (ORCID: https://orcid.org/0000-0003-3857-1688)
- Wu‐Chou Su (ORCID: https://orcid.org/0000-0003-2953-4105)
- Maulik R Patel (ORCID: https://orcid.org/0000-0003-3749-0122)
- Jaehyung Hong (ORCID: https://orcid.org/0009-0005-7898-3670)
- Marc Oliva (ORCID: https://orcid.org/0000-0001-5352-8130)
- Sonali Jindal (ORCID: https://orcid.org/0000-0002-3911-6815)
- John Engelhardt (ORCID: https://orcid.org/0009-0009-5205-4581)
- Tolga Turan (ORCID: https://orcid.org/0000-0002-3333-3851)
- Agostina Stradella (ORCID: https://orcid.org/0000-0002-2307-8869)
- Christophe Le Tourneau (ORCID: https://orcid.org/0000-0001-9772-4686)
- Amani Makkouk (ORCID: https://orcid.org/0000-0002-5212-0181)
- Alexander Dimitrios Colevas (ORCID: https://orcid.org/0000-0003-3849-4264)
- Amita Patnaik (ORCID: https://orcid.org/0000-0002-4144-2193)
- Michael A. McDevitt (ORCID: https://orcid.org/0000-0003-0031-5881)
- Martha Elizabeth Blaney
- John D. Powderly (ORCID: https://orcid.org/0000-0002-7608-0380)
- Chia-Chi Lin
- Alexander I. Spira
- Toshio Shimizu
- Padmanee Sharma
Institutions
- Prisma Health (US)
- The University of Texas MD Anderson Cancer Center (US)
- Université Paris-Saclay (FR)
- AbbVie (United States) (US)
- Carolina BioOncology Institute (US)
- Centre Léon Bérard (FR)
- Institut Català d'Oncologia (ES)
- South Texas Accelerated Research Therapeutics (US)
- Virginia Cancer Specialists (US)
- Hospital Universitario Fundación Jiménez Díaz (ES)
- National Taiwan University Hospital (TW)
- National Cancer Center Hospital East (JP)
- National Cheng Kung University Hospital (TW)
- Stanford Cancer Institute (US)
- National Cancer Center Hospital (JP)
- Stanford University (US)
Publication Details
- Journal
- Future Oncology
- Published
- 2026-10-29
- DOI
- https://doi.org/10.1080/14796694.2026.2736946
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- AbbVie