770 Safety, efficacy, and pharmacokinetic results from a phase I first-in-human study of ABBV-151 with or without anti-PD1 mAb (budigalimab) in patients with locally advanced or metastatic solid tumors

作者：Anthony W. Tolcher, Desamparados Roda-Perez, Kai He, Vı́ctor Moreno, Carlos Gomez‐Roca, Jean‐Pascal Machiels, Albiruni R. Abdul Razak, Mohammad Sahtout, Xiaowen Guan, Stacy Jaryno-Daly, Rachel S. Leibman, Martha Blaney, James J. O’Brien, Patricia LoRusso, John D. Powderly, Talia Golan, Kathy D. Miller, Jordi Bruix · 发表于：Regular and Young Investigator Award Abstracts · 年份：2022 · DOI：10.1136/jitc-2022-sitc2022.0770 · 被引用次数：5 · 研究领域：Cancer Immunotherapy and Biomarkers、Colorectal Cancer Treatments and Studies、Pancreatic and Hepatic Oncology Research

Background Glycoprotein-A repetitions predominant (GARP) is expressed on regulatory T-cells and modulates release of active transforming growth factor β1 (TGFβ1), an immunosuppressive cytokine. ABBV-151 is a first-in-class monoclonal antibody (mAb) that binds to the GARP-TGFβ1 complex, blocking the release of active TGFβ1. Preclinical data demonstrate that blocking GARP-TGFβ1 and programmed cell death protein-1 (PD-1) improves antitumor efficacy compared with anti–PD-1 alone. Combining ABBV-151 with the anti–PD-1 mAb budigalimab may enable increased antitumor efficacy by reducing the immunosuppressive effects of TGFβ1. Herein, we report preliminary safety, efficacy, and pharmacokinetic (PK) results from a first-in-human, phase 1 study (NCT03821935) assessing ABBV-151 ± budigalimab in adult patients (≥18 years) with locally advanced/metastatic solid tumors. Results from the all-comer dose escalation (ESC) phase and two cohorts from the dose expansion (EXP) phase are available: anti-PD-1/PD-ligand (L)1 naïve hepatocellular carcinoma (HCC) and anti-PD-1/PD-L1 relapsed/refractory urothelial cancer (UC). Methods ESC patients must be refractory/intolerant to existing effective therapies; EXP cohorts have tumor-specific eligibility requirements. The primary ESC endpoint is the recommended phase II dose of ABBV-151 ± budigalimab. The primary EXP endpoint is preliminary efficacy of ABBV-151 + budigalimab, assessed by objective response rate per Response Evaluation Criteria in Solid...