First-in-human phase I open-label study of the LAG-3 antagonist antibody INCAGN02385 in patients with select advanced or metastatic solid tumors
The Oncologist, 2025
Powderly J., Gutierrez M., Balmanoukian A., Hoyle P., Dong Z., Cheng L., Chen X., Janik J., Bourayou N., Hamid O.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Oncology Immunotherapy | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
Background
Immune checkpoint receptor lymphocyte-activation gene 3 (LAG-3) is an activation marker for CD4+ and CD8+ T cells. Prolonged LAG-3 expression downregulates T-cell activation; therefore, LAG-3 blockade may restore antitumor immune response. INCAGN02385 is a humanized monoclonal LAG-3-targeting antibody. This first-in-human phase I study evaluated INCAGN02385 for advanced/metastatic solid tumors.
Materials and Methods
In this dose escalation study, patients with select immunogenic advanced or metastatic solid tumors received a single INCAGN02385 infusion (25 mg to 750 mg) every 2 weeks (Q2W). Objectives included evaluation of safety/tolerability, maximum tolerated dose (MTD) (primary), pharmacokinetics (PK), antitumor activity (secondary).
Results
Twenty-two patients were enrolled and treated. Sixty-four percent had received ≥ 3 lines of systemic therapy. Sixty-eight percent had received prior immune checkpoint inhibitor (ICI) therapy; anti–programmed death protein-1/anti–programmed death ligand-1, 68%, anti–cytotoxic T-lymphocyte-associated protein-4 therapy, 18%. No dose-limiting toxicities occurred, and an MTD was not reached. Sixteen patients (73%) experienced treatment-related adverse events (TRAEs), most frequently fatigue (n = 7). Except for one grade 3 lymphopenia TRAE, all were grade 1/2 severity. Two patients experienced sponsor-assessed immune-related AEs (pneumonitis, peripheral sensory neuropathy [n = 1] patient each). INCAGN02385 PK parameters were dose proportional across all doses evaluated. Six patients achieved stable disease lasting ≥ 56 days (range, 57-413 days).
Conclusions
INCAGN02385 exhibited linear PK and preliminary evidence of disease control in this heavily pretreated population, consistent with other LAG-3-targeting monotherapies. A 350-mg Q2W dose was selected for phase II studies that will focus on combinations of INCAGN02385 with other ICIs.