First-in-Human Phase I Study of Aprutumab Ixadotin, a Fibroblast Growth Factor Receptor 2 Antibody–Drug Conjugate (BAY 1187982) in Patients with Advanced Cancer

Abstract

Background

Fibroblast growth factor receptor (FGFR) 2 is overexpressed in several tumor types, including triple-negative breast cancer and gastric cancer, both of which have a high unmet medical need. Aprutumab ixadotin (BAY 1187982) is the first antibody–drug conjugate (ADC) to target FGFR2 and the first to use a novel auristatin-based payload.

Objective

This first-in-human trial was conducted to determine the safety, tolerability, and maximum tolerated dose (MTD) of aprutumab ixadotin in patients with advanced solid tumors from cancer indications known to be FGFR2-positive.

Patients and Methods

In this open-label, multicenter, phase I dose-escalation trial (NCT02368951), patients with advanced solid tumors received escalating doses of aprutumab ixadotin (starting at 0.1 mg/kg body weight), administered intravenously on day 1 of every 21-day cycle. Primary endpoints included safety, tolerability, and the MTD of aprutumab ixadotin; secondary endpoints were pharmacokinetic evaluation and tumor response to aprutumab ixadotin.

Results

Twenty patients received aprutumab ixadotin across five cohorts, at doses of 0.1–1.3 mg/kg. The most common grade ≥ 3 drug-related adverse events were anemia, aspartate aminotransferase increase, proteinuria, and thrombocytopenia. Dose-limiting toxicities were thrombocytopenia, proteinuria, and corneal epithelial microcysts, and were only seen in the two highest dosing cohorts. The MTD was determined to be 0.2 mg/kg due to lack of quantitative data following discontinuations at 0.4 and 0.8 mg/kg doses. One patient had stable disease; no responses were reported.

Conclusions

Aprutumab ixadotin was poorly tolerated, with an MTD found to be below the therapeutic threshold estimated preclinically; therefore, the trial was terminated early.

ClinicalTrials.gov Identifier

NCT02368951.

Electronic supplementary material

The online version of this article (10.1007/s11523-019-00670-4) contains supplementary material, which is available to authorized users.