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Background Increased transforming growth factor beta (TGFβ) signaling in the tumor microenvironment is associated with immune cell exclusion and poor clinical outcomes. CRB-601 is a humanized monoclonal antibody that targets integrin αvβ8, preventing activation of the latent TGFβ complex. In preclinical studies, CRB-601 exhibited dose-dependent antitumor activity, decreased TGFβ-1 signaling in the tumor microenvironment and enhanced the efficacy of programmed cell death protein-1 (PD-1) inhibitors. 1–3 Here, we report initial results from the first-in-human phase 1/2 study of CRB-601 (NCT06603844).Methods Adults with selected advanced or metastatic solid tumors and progressive disease after ≥1 line of therapy were enrolled in the dose-escalation stage of the trial. Patients received CRB-601 monotherapy at doses of 3, 10 or 30 mg/kg once every 2 weeks during 28-day cycles. A Bayesian Optimal Interval design was used to determine the maximum tolerated dose and/or the pharmacologically active dose range. Safety, antitumor activity, baseline avβ8 target levels and pharmacokinetics (PK) were also assessed.Results As of May 12, 2025, 25 patients had enrolled in the dose-escalation phase of the study and received CRB-601 (3 mg/kg, n=8; 10 mg/kg, n=10; 30 mg/kg, n=7), of whom 13 (52%) were female and 19 (76%) were White. The mean (standard deviation) age was 62.5 (±12.19) years, and the median (range) number of previous lines of therapy was 3 (1–9). The most common tumor types were head and neck squamous cell carcinoma (n=6), melanoma and ovarian cancer (each n=4). A total of 83 treatment-emergent adverse events (TEAEs) were reported in 21 patients. Nausea, anemia and vomiting were the most common TEAEs (all ≥ 15% of patients). Grade 3 TEAEs were reported in 8 patients, with only one event, pruritus, deemed related to CRB-601. There were no grade 4 or 5 TEAEs, or dose-limiting toxicities. Antitumor activity, biomarker and PK data will be presented at the congress.Conclusions Early phase 1/2 results suggest that CRB-601 is well tolerated with a favorable safety profile. These initial results suggest that further dose exploration with CRB-601 either alone or in combination with a PD-1 inhibitor is warranted.Trial Registration ClincalTrials.gov NCT06603844References Shinde V, Wang D, Memon D, et al. CRB-601, an integrin avβ8 blocking antibody entering phase I: pre-clinical and translational biomarkers for indication selection [Poster]. Presented at the 38th meeting of the Society for the Immunotherapy of Cancer, Nov 1–5, 2023, San Diego, CA, USA.Singh M, Wang D, Shinde V, et al. CRB-601, a selective integrin αvβ8-blocking antibody, prevents TGFβ activation, promotes immune cell remodeling, and exhibits potent antitumor activity [Poster]. Presented at the 38th meeting of the Society for the Immunotherapy of Cancer, Nov 1–5, 2023, San Diego, CA, USA.Wang D, Shinde V, Singh M, Brake R, Kolodziej A. CRB-601, an αvβ8 blocking antibody, prevents activation of TGFβ and exhibits anti-tumor activity associated with immune cell remodeling of the tumor microenvironment [Poster]. Presented at the annual meeting of the American Association of Cancer Research, April 14–19, 2023, Orlando, FL, USA.Ethics Approval Nebraska Hematology Oncology WCG 20243082 START - San Antonio Salus IRB START2023.01 Sarah Cannon - SCRI Oncology Partners Castle IRB IORG0010151 Sarah Cannon - OU Health Stephenson Cancer Center Castle IRB IORG0010151 AdventHealth Oncology Hematology WCG 20243082 Sarah Cannon - Florida Cancer Specialists/Lake Nona Castle IRB IORG0010151 University Hospital Cleveland University Hospitals IRB 20241088 Cedars-Sinai Medical Center Cedars-Sinai Office of Research Compliance and Quality Improvement 167906 UC San Diego WCG 20243082 The Clatterbridge Cancer Center NHS Foundation Trust UK London Bridge Research Ethics Committee 24/LO/0802 The University of Edinburgh - Western General Hospital - Edinburgh Cancer Research UK Centre London Bridge Research Ethics Committee 24/LO/0802