1076TiP First-in-human study of ABBV-514 as monotherapy and in combination with budigalimab in patients with advanced solid tumors

Regulatory T-cells (Tregs) are specialized T-cells that can inhibit antitumor immune responses, and high intratumoral Treg levels have been associated with negative outcomes in cancer. Chemokine receptor (CCR)8 is preferentially expressed on tumor-infiltrating Tregs, relative to peripheral blood Tregs and effector T cells. ABBV-514 is an afucosylated monoclonal antibody that binds CCR8 and is designed to enhance antibody-dependent cellular cytotoxicity to deplete tumor-infiltrating Tregs. This first-in-human trial evaluates safety, pharmacokinetics (PK), and preliminary efficacy of ABBV-514 as monotherapy and in combination with budigalimab (BDG), a PD-1–blocking antibody. This is a multicenter phase 1 dose-escalation/expansion study (NCT05005403). Eligible patients (≥18 years) have evaluable or measurable disease per RECIST v1.1 and ECOG performance status ≤1. Primary objectives are to assess safety, tolerability, and PK and to determine the maximum tolerated/maximum administered dose of ABBV-514 as monotherapy and in combination with BDG. Secondary and exploratory objectives are to evaluate immunogenicity of ABBV-514 as mono- or combination therapy, to assess preliminary efficacy (objective response rate per RECIST v1.1 criteria, clinical benefit rate, duration of response, progression-free survival), and to evaluate pharmacodynamics and predictive biomarkers. Patients are treated until disease progression or intolerable toxicity. Dose escalation will be guided by a Bayesian optimal interval design. Planned enrollment is 176 patients: up to 140 in dose escalation and 36 in dose expansion. In dose escalation, patients with relapsed/refractory (R/R) solid tumors will be enrolled in ABBV-514 monotherapy (N≤55) or ABBV-514 + BDG (N≤55) cohorts; up to 30 additional patients will be included in paired biopsy cohorts. In dose expansion, patients with R/R non-small cell lung cancer will be enrolled in ABBV-514 monotherapy (N=12) and ABBV-514 + BDG (N=12) cohorts, and patients with R/R head and neck squamous cell carcinoma in an ABBV-514 + BDG (N=12) cohort. Enrollment initiated in November 2021, with 30 patients enrolled as of April 2023. NCT05005403. Medical writing support was provided by Iratxe Abarrategui, PhD, CMPP, from Aptitude Health, The Hague, the Netherlands, and funded by AbbVie. AbbVie. AbbVie.