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First-in-human phase I open-label study of the anti–TIM-3 monoclonal antibody INCAGN02390 in patients with select advanced or metastatic solid tumors

The Oncologist, 2025

Gutierrez M., Tang S., Powderly J., Balmanoukian A., Hoyle P., Dong Z., Cheng L., Gong X., Janik J., Bourayou N., Hamid O.

Disease areaApplication areaSample typeProducts
Oncology
Immunotherapy
Pathophysiology
Plasma
Olink Target 96

Olink Target 96

Abstract

Background

T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) is an immune checkpoint receptor upregulated during anti-programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) immunotherapy for cancer. TIM-3 blockade may improve the antitumor activity of PD-1/PD-L1inhibition. This phase 1 study evaluated INCAGN02390, a novel, fully human Fc-engineered antibody against TIM-3.

Methods

INCAGN02390 was evaluated by dose escalation at 10-1600 mg infused in 14-day cycles (every 2 weeks [Q2W]) in pretreated patients with select advanced/metastatic immunogenic solid tumors. Objectives included evaluation of safety/tolerability and maximum tolerated dose (MTD) (primary), pharmacokinetics, preliminary antitumor activity, pharmacodynamics, and immunogenicity (secondary).

Results

Forty patients were enrolled and treated with INCAGN02390; 60% had previously received ≥3 lines of systemic therapy. Forty-eight percent had received a prior immune checkpoint inhibitor (anti−PD-1/PD-L1 therapy, 43%; anti-cytotoxic T-lymphocyte associated protein-4 therapy, 23%). No dose-limiting toxicities (DLTs) were observed and MTD was not reached. Twelve patients (30%) had treatment-related adverse events (TRAEs), most commonly fatigue and pruritus (n = 3 each); 3 (8%) had grade ≥3 TRAEs. Four patients (10%) experienced sponsor-assessed irAEs. One patient (3%) achieved partial response (duration, 5.7 months) and 6 had stable disease (≥56 days in all patients, >18 months in 2 patients).

Conclusions

In this heavily pretreated population, no DLTs were reported and modest efficacy was exhibited. A 400-mg Q2W dose was selected for phase II studies investigating INCAGN02390 as part of combination immunotherapies for advanced cancers.

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