Abstract 596TiP
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 I, 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 II 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.
Clinical trial identification
NCT03821935.
Editorial acknowledgement
Medical writing support was provided by Judith Land, PhD, from Aptitude Health, The Hague, the Netherlands, and funded by AbbVie.
Legal entity responsible for the study
AbbVie.
Funding
AbbVie Inc.
Disclosure
J. Powderly: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Carolina BioOncology Institute; Leadership role, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment, BioCytics is developing intellectual property for cellular immunotherapy: BioCytics; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca/MedImmune; Advisory/Consultancy: Curis; Advisory/Consultancy, Research grant/Funding (institution): TopAlliance Biosciences Inc.; Speaker Bureau/Expert testimony: Dendreon; Speaker Bureau/Expert testimony: Merck; Shareholder/Stockholder/Stock options: Lion Biotechnologies; Shareholder/Stockholder/Stock options: Juno Therapeutics; Shareholder/Stockholder/Stock options: Bluebird Bio; Shareholder/Stockholder/Stock options: Kite Pharma; Shareholder/Stockholder/Stock options: Ziopharm Oncology; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Lilly/ImClone; Research grant/Funding (institution): MacroGenics; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Corvus Pharmaceuticals; Research grant/Funding (institution): Curis. T. Shimizu: Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Takeda Oncology; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Chordia Therapeutics; Research grant/Funding (institution): 3D-Medicine; Research grant/Funding (institution): SymBio Pharmaceuticals; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): FivePrime; Research grant/Funding (institution): AstraZeneca; Honoraria (self), Regular member of IRB Scientific Review: the Consortium on Harmonization of Institutional Requirements for Clinical Research (CHAIR), HKSAR, China. P. Lorusso: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Genmab; Advisory/Consultancy: Genentech; Advisory/Consultancy: CytomX; Advisory/Consultancy: Takeda; Advisory/Consultancy: Cybrexa; Advisory/Consultancy: Agenus; Advisory/Consultancy: IQVIA; Advisory/Consultancy: TRIGR; Advisory/Consultancy: Pfizer; Advisory/Consultancy: I-Mab; Advisory/Consultancy: ImmunoMet; Advisory/Consultancy: Black Diamond; Advisory/Consultancy: GlaxoSmith Kline; Advisory/Consultancy: QED Therapeutics; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Shattuck; Advisory/Consultancy: Astellas; Advisory/Consultancy: Salarius; Advisory/Consultancy: Silverback; Advisory/Consultancy: MacroGenics; Advisory/Consultancy: Kyowa Kirin; Advisory/Consultancy: Kineta; Advisory/Consultancy: Zentalis; Advisory/Consultancy: Molecular Templates; Advisory/Consultancy, Data safety monitoring board: Agios; Advisory/Consultancy, Data safety monitoring board: FivePrime; Advisory/Consultancy, Data safety monitoring board: Halozyme; Advisory/Consultancy, Data safety monitoring board: Tyme; Advisory/Consultancy, Alliance member: Roche/Genentech; Advisory/Consultancy, Consultant: SOTIO. A. Razak: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: Merck; Research grant/Funding (institution): CASI Pharmaceuticals; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Deciphera; Research grant/Funding (institution): Karypharm Therapeutics; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Boston Biomedical; Research grant/Funding (institution): BMS; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Blueprint Medicines; Research grant/Funding (institution): Merck; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Adaptimmune. A.V. Balar: Honoraria (self), Advisory/Consultancy: Genentech/Roche; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Nektar; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy: Dragonfly Therapeutics; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Shareholder/Stockholder/Stock options, Officer/Board of Directors, Equity and SAB member: Epivax Oncology Inc.. J. Bruix: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Adaptimmune; Advisory/Consultancy: ArQule; Advisory/Consultancy: AstraZeneca/MedImmune; Advisory/Consultancy: Basilea; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, paid conference attendance: Bayer; Advisory/Consultancy: BioAlliance; Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, paid conference attendance: BTG; Honoraria (self), Advisory/Consultancy: Eisai; Advisory/Consultancy: Gilead; Advisory/Consultancy: Incyte; Advisory/Consultancy: Kowa; Advisory/Consultancy: Lilly; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Nerviano; Advisory/Consultancy: Novartis; Advisory/Consultancy: Quirem; Advisory/Consultancy: Roche; Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy: Sirtex; Honoraria (self), Advisory/Consultancy: Terumo; Honoraria (self), Travel/Accommodation/Expenses, paid conference attendance: Ipsen. M. Blaney: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. X. Guan: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. S. Lacy: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. S. Lally: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. S. Lambert: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. R. Leibman: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. G. Vosganian: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. T. Golan: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: AbbVie; Advisory/Consultancy: Teva; Advisory/Consultancy: Bayer; Speaker Bureau/Expert testimony: Bioline. A. Tolcher: Advisory/Consultancy: AbbVie. All other authors have declared no conflicts of interest.