ABBV-368 is a novel humanized IgG1 agonist monoclonal antibody specific for human OX40, a TNF receptor superfamily member expressed on activated and memory T-cell subsets, as well as T regulatory cells. The proposed ABBV-368 therapeutic mechanism of action includes activation of T effector cells and inhibition of the suppressive capacity of T regulatory cells. This ongoing first-in-human, phase 1, two-part study (NCT03071757) is investigating the safety, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary antitumor activity of ABBV-368 in patients (pts) with advanced solid tumors.
Eligible pts include adults (≥18 years) with advanced or metastatic solid tumors. ABBV-368 was administered intravenously in a 3 + 3 dose-escalation design at doses ranging from 0.01 to 3.0 mg/kg every 2 weeks (4 cohorts). PK was assessed in cycle 1 and cycle 3. OX40 receptor saturation, Ki67 proliferation marker expression in peripheral blood immune cell subsets, and additional PD biomarkers were evaluated.
As of Feb 12, 2018, 38 pts with advanced or metastatic tumors were enrolled in dose-escalation cohorts. Median age was 65 years (range, 38–78). No dose-limiting toxicities were reported during dose escalation. Overall, 15 (39.5%) pts reported grade (Gr) ≥3 treatment-emergent adverse events (TEAEs). Three (7.9%) pts reported Gr ≥ 3 TEAEs related to ABBV-368. Two investigator-reported immune-related AEs were documented, including hypothyroidism; neither were serious. ABBV-368 PK was approximately dose-proportional from 0.1- to 3-mg/kg doses during cycle 1, with dose-dependent target saturation. Initial antitumor activity has been observed. Updated safety, PK, PD, and efficacy data will be reported.
ABBV-368 was well tolerated; a maximum tolerated dose was not reached. Antitumor activity was observed at doses predicted to be biologically active. Further evaluation of ABBV-368 is ongoing in pts with advanced solid tumors.
Clinical trial identification
Legal entity responsible for the study
Medical writing support was provided by Mary L. Smith, PhD, CMPP, from TRM Oncology, Atlanta, GA, and funded by AbbVie.
A. Spira: Consultant and Institutional research support: AbbVie. A. Patnaik: Research grants to institution: Merck & Co., Inc. LG; Advisory board member: Merck & Co., Inc., AstraZeneca, AbbVie, Pfizer, Genentech/Roche; Research grant: Bristol-Myers Squibb. A.W. Tolcher: Consultant: AbbVie. M.E. Blaney, A. Parikh, A. Reddy, W. Henner, M. McDevitt, D. Afar: Employee and may own stock: AbbVie. J. Powderly: Employee and leadership role: Carolina BioOncology Institute PLLC; Stock/ownership: Iovance, Juno, Bluebird Bio, Kite Pharma, ZioPharm; Speaker bureau: Genentech, Bristol-Myers Squibb, Merck; Research funding: AstraZeneca, Genentech, Clovis, Corvus, Incyte, AbbVie, Bristol-Myers Squibb, MacroGenics; Patent or intellectual property: Founder of BioCytics, developing T-cell immunotherapies. All other authors have declared no conflicts of interest.