Phase 1a/1b study of first-in-class B7-H4 antibody, FPA150, as monotherapy in patients with advanced solid tumors.

Abstract

2529Background: B7-H4, a transmembrane protein of the B7 family, is a negative regulator of T cell function, expressed at high levels on several cancers, including approximately 50% of breast, ovarian and endometrial cancers. FPA150 is a fully human antibody against B7-H4 that blocks inhibition of T cell activity and has enhanced antibody-dependent cell-mediated cytotoxicity. It is the first therapeutic molecule targeting B7-H4 to enter the clinic. We report preliminary results from an ongoing phase 1a/1b study of FPA150 in advanced solid tumors. Methods: Phase 1a included dose escalation in which B7-H4-unselected patients with advanced solid tumors were treated with FPA150 at doses between 0.01 to 20 mg/kg every three weeks (Q3W) in an accelerated titration followed by 3+3 design and a separate dose exploration cohort in which B7-H4+ (H-score≥100) patients were treated at doses of 3 or 10 mg/kg Q3W with mandatory pre- and on-treatment biopsies. Results: As of 12/31/2018, 24 patients with a median of 3 prior therapies were treated with FPA150, 6 of whom were in the B7-H4+ dose exploration cohort. Seven patients from dose escalation were also retrospectively identified as B7-H4+. Most patients received FPA150 at 3 mg/kg (n=8) or 10 mg/kg (n=6). Median number of doses was 3 (range 1-11). No dose-limiting toxicities or treatment-related serious adverse events were reported, and there were no treatment-related AEs (TRAEs) leading to discontinuation of FPA150. Most TRAEs were Grade 1-2, with diarrhea and fatigue most common (16.7%). Grade 3 TRAE hypertension occurred in 1 patient. FPA150 displayed approximately dose-proportional exposure at doses ≥0.3 mg/kg with half-life of 1-2 weeks. Conclusions: FPA150 monotherapy demonstrated a favorable safety profile and evaluation of anti-tumor activity is ongoing. 20 mg/kg Q3W was selected as the recommended dose. Phase 1b enrollment of FPA150 monotherapy in patients with B7-H4+ breast, ovarian and endometrial cancer began in February 2019. We will present updated safety, PK, and preliminary biomarker and efficacy data. Clinical trial information: NCT03514121.