Document Type
Article
Publication Date
7-9-2025
Publication Title
Oncologist
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.
PubMed ID
40631773
Volume
30
Issue
7
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Gutierrez, Martin E.; Tang, Shou Ching; Powderly, John D.; Balmanoukian, Ani S.; Hoyle, Paul E.; Dong, Zhiwan; Cheng, Lulu; Gong, Xiaohua; Janik, John E.; Bourayou, Nawel; and Hamid, Omid, "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" (2025). School of Medicine Faculty Publications. 3929.
https://digitalscholar.lsuhsc.edu/som_facpubs/3929
10.1093/oncolo/oyaf144
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