Exploratory pharmacodynamics (PD) trial to investigate the mechanism of action of RG7160 (GA201), a novel dual-acting, monoclonal antibody (mAb) designed to enhance antibody-dependent cellular cytotoxicity (ADCC), compared with cetuximab (C) in neoadjuvant head and neck squamous cell carcinoma (HNSCC).

Abstract

5522 Background: GA201 efficacy was superior to C in orthotopic xenograft models in terms of activity and PD. In a phase I study, objective responses and long lasting stable disease were observed in heavily pre-treated patients (pts). Methods: HNSCC pts (T2-4, any N, M0) received i.v. neo-adjuvant 700/1400 mg GA201 or C (as per SPC), on D1 and 8. Tumor biopsies were taken at baseline (BL) and pre-surgery. The primary objective was determination of changes in tumor immune cell infiltration after treatment. Peripheral CD3+, CD16+, CD56+ cells, plasma cytokines, tumor EGFR and 18F-FDG-PET avidity were also studied. Results: To date, 39 pts (15/10 vs 14 pts for 700/1400 GA201 vs C, respectively) were evaluable for the primary objective and 4 pts are on-going. Patient characteristics at BL were as follows: median age, 57/62 vs 62 years; gender, 11/10 vs 12 male; tumor size ≤ 4 cm, 7/3 vs 3 pts. A greater proportion of pts receiving GA201 compared to C had metabolic tumor reduction (> 25% of SUVmax) (10/15 at 700 mg [1 pathological CR], 7/10 at 1400 mg GA201 vs 7/14 C pts) and symptomatic relief (6/12 at 700 mg, 6/7 at 1,400 mg GA201 vs 2/10 C pts). Table shows changes in PD markers. Conclusions: GA201 treatment, compared to C, exhibited more extensive tumor immune cell infiltration and a greater metabolic response. Consistent with the proposed mechanism of action of GA201, peripheral NK cells dropped and a unique cytokine profile was observed. The data support the immunomodulatory superiority of GA201 - a mAb designed to enhance ADCC compared to C. [Table: see text]