MDX-124, a first-in-class annexin-A1 targeting antibody, in patients with locally advanced or metastatic solid malignancies: Data supporting RP2D from the dose escalation stage of a first-in-human phase Ib trial.

e15112 Background: Annexin-A1 overexpression correlates with tumor proliferation and poor prognosis in cancer making it a novel therapeutic target. MDX-124 is a first-in-class monoclonal antibody that targets annexin-A1. In preclinical models, MDX-124 significantly inhibits tumor growth and metastasis, induces antibody-dependent cellular cytotoxicity and has demonstrated synergy with several chemotherapeutics. Here we report safety and efficacy data from a first-in-human phase Ib study of MDX-124 in patients with advanced or metastatic solid malignancies. Methods: This modular, multi-arm, phase Ib study of MDX-124 is enrolling adult patients with solid tumors likely to overexpress annexin-A1. Module 1 is a single agent dose escalation using a BOIN (Bayesian Optimal Interval) design with an expansion cohort in which MDX-124 is administered Q2W at doses ranging from 1–30 mg/kg with a 21-day DLT period. The primary objective is to determine the recommended phase 2 dose (RP2D) of MDX-124 as monotherapy. Secondary objectives are to evaluate safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of MDX-124. Responses are evaluated according to RECIST v1.1. Adverse events are graded using CTCAE v5.0. Tumor and immunological biomarkers are exploratory endpoints. Module 2 will assess MDX-124 as monotherapy and in combination with SOC therapies in indication-specific arms using a standard 3+3 design. Results: At data cut-off, 21 patients received MDX-124 at doses ranging from 1–30 mg/kg (mean age 60 years, 10 primary tumor types and median of 3 prior treatment lines). A disease control rate of 55% (6/11) was observed in evaluable patients, including 3/4 cholangiocarcinoma patients with one confirmed partial response. No grade 3-4 treatment related adverse events (TRAEs) or DLTs were reported. TRAEs were reported in 62% patients with fatigue and nausea being most common (33%). PK data show dose proportional increase in serum concentration of MDX-124 across 1-30 mg/kg cohorts. Conclusions: Data indicate promising safety, tolerability, and anti-tumor activity of MDX-124. The RP2D for MDX-124 monotherapy was determined to be 20 mg/kg Q2W. Module 2 is currently enrolling. Clinical trial information: ISRCTN78740398.