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, Hamid Omid
John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ 07601, USA.
Louisiana State University (LSU) Health Sciences Center, New Orleans, LA 70112, USA.
Oncologist. 2025 Jul 4;30(7). doi: 10.1093/oncolo/oyaf144.
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.
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).
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).
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.
含T细胞免疫球蛋白和粘蛋白结构域蛋白3（TIM-3）是一种免疫检查点受体，在癌症的抗程序性死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）免疫治疗期间上调。TIM-3阻断可能会提高PD-1/PD-L1抑制的抗肿瘤活性。这项1期研究评估了INCAGN02390，一种新型的、完全人源化的经Fc工程改造的抗TIM-3抗体。
在经预处理的患有特定晚期/转移性免疫原性实体瘤的患者中，以10 - 1600 mg的剂量递增进行评估，每14天为一个周期（每2周一次[Q2W]）静脉输注INCAGN02390。目标包括评估安全性/耐受性和最大耐受剂量（MTD）（主要目标）、药代动力学、初步抗肿瘤活性、药效学和免疫原性（次要目标）。
40名患者入组并接受了INCAGN02390治疗；60%的患者此前接受过≥3线的全身治疗。48%的患者曾接受过先前的免疫检查点抑制剂治疗（抗PD-1/PD-L1治疗，43%；抗细胞毒性T淋巴细胞相关蛋白4治疗，23%）。未观察到剂量限制性毒性（DLT），也未达到MTD。12名患者（30%）发生了与治疗相关的不良事件（TRAEs），最常见的是疲劳和瘙痒（各n = 3）；3名患者（8%）发生了≥3级TRAEs。4名患者（10%）经历了申办方评估的免疫相关不良事件（irAEs）。1名患者（3%）获得部分缓解（持续时间，5.7个月），6名患者病情稳定（所有患者≥56天，2名患者>18个月）。
在这个经过大量预处理的人群中，未报告DLT，且显示出一定疗效。选择每2周一次400 mg的剂量用于II期研究，将INCAGN02390作为晚期癌症联合免疫治疗的一部分进行研究。
