Abstract CT207: Phase 1 first-in-human study of ABBV-151 as monotherapy or in combination with budigalimab in patients with locally advanced or metastatic solid tumors
Authors: Powderly John , Shimizu Toshio , LoRusso Patricia , Razak Albiruni , Miller Kathy , Balar Arjun , Bruix Jordi , Michel Loren , Blaney Martha , Guan Xiaowen , Lacy Susan , Lally Satwant , Lambert Stacie , Leibman Rachel , Vosganian Gregory , Golan Talia , Tolcher Anthony 
Published: July 2021

Background Glycoprotein-A repetitions predominant (GARP) regulates membrane-bound 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 and blocks TGFβ1 release. Preclinical data demonstrated that targeting both GARP-TGFβ1 and programmed cell death protein 1 (PD-1) improved antitumor effects compared with anti-PD-1 alone. Combining ABBV-151 with the anti-PD-1 mAb budigalimab (ABBV-181) may enable a more effective antitumor immune response by reducing the immunosuppressive effect of TGFβ1. Trial design This is a multicenter phase 1, dose escalation and dose expansion study (NCT03821935) in patients (pts; ≥18 yr, Eastern Cooperative Oncology Group performance status 0-1) with locally advanced or metastatic solid tumors. The primary objective of dose escalation is to determine the recommended phase 2 dose (RP2D) of ABBV-151 as monotherapy or with budigalimab; dose expansion will assess the objective response rate of ABBV-151 ± budigalimab. Secondary/exploratory objectives include assessing preliminary efficacy, safety, tolerability, pharmacokinetics (PK), and evaluating potential pharmacodynamic and predictive biomarkers. Dose escalation of ABBV-151, guided by a Bayesian optimal interval design, will assess dose-limiting toxicities during the first 28-day cycle and will be utilized until the RP2D is defined. ABBV-151 + budigalimab (fixed dose) will start ≥2 dose levels below that proven safe for ABBV-151. Adverse events will be evaluated per National Cancer Institute Common Terminology Criteria v5.0. Response will be assessed using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 and iRECIST every 8 weeks. PK of ABBV-151 will be characterized. Saturation of GARP-TGFβ1 on platelets and PD-1 on CD4 T cells will be determined. Modulation of cytokines, chemokines, lymphocyte activity, and gene expression will be assessed in blood, while gene signatures and protein markers will be explored in tumor tissues. Baseline tumor characteristics will be retrospectively related to response. Enrollment initiated Mar 2019, with 37 pts enrolled as of May 2020.

Citation Format: John Powderly, Toshio Shimizu, Patricia LoRusso, Albiruni Razak, Kathy Miller, Arjun Balar, Jordi Bruix, Loren Michel, Martha Blaney, Xiaowen Guan, Susan Lacy, Satwant Lally, Stacie Lambert, Rachel Leibman, Gregory Vosganian, Talia Golan, Anthony Tolcher. Phase 1 first-in-human study of ABBV-151 as monotherapy or in combination with budigalimab in patients with locally advanced or metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT207.