ABBV-184 是一种新型生存素肽靶向 T 细胞受体 (TCR)/抗 CD3 双特异性蛋白，已证明对 HLA-A2:01 阳性肿瘤系具有临床前 T 细胞激活和细胞毒性。这项首次人体试验评估了 ABBV-184 单药治疗急性髓系白血病 (AML) 和非小细胞肺癌 (NSCLC) 患者的效果。这项 1 期多中心、开放标签、剂量递增试验 (NCT04272203) 招募了成年患者具有 HLA-A2:01 限制基因型的复发/难治性 AML 或 NSCLC。患者最初接受 0.07 ug/kg 剂量的 ABBV-184，剂量增加 2 至 3 倍。主要目标是确定 ABBV-184 推荐的 2 期剂量。次要目标包括安全性、耐受性、药代动力学和免疫原性评估。 15 名患者参加了剂量递增（8 名 AML 和 7 名 NSCLC）。 ABBV-184 剂量范围为 0.07mg/kg-0.7μg/kg，半衰期约为 13-29 小时。在所有剂量水平下均观察到短暂的细胞因子增加，并且在 NSCLC 患者中观察到短暂的外周血淋巴细胞减少。最常报告的治疗引起的不良事件（TEAE）是贫血、腹泻和头痛。报告了 1-2 级输注相关反应 (IRR) 和细胞因子释放综合征 (CRS) TEAE。ABBV-184 耐受性良好，并证明了 CD3 与短暂细胞因子增加和外周淋巴细胞减少有关的初步证据。NCT04272203。

ABBV-184, a novel survivin peptide-targeting T-cell receptor (TCR)/anti-CD3 bispecific protein, demonstrated preclinical T-cell activation and cytotoxicity toward HLA-A2:01-positive tumor lines. This first-in-human trial evaluated ABBV-184 monotherapy in patients with acute myeloid leukemia (AML) and non-small cell lung cancer (NSCLC).This phase 1 multicenter, open-label, dose escalation trial (NCT04272203) enrolled adult patients with relapsed/refractory AML or NSCLC with an HLA-A2:01 restricted genotype. Patients received ABBV-184 at 0.07 ug/kg initially, with 2- to 3-fold dose increases. The primary objective was determining the ABBV-184 recommended phase 2 dose. Secondary objectives included safety, tolerability, pharmacokinetics, and immunogenicity assessments.Fifteen patients enrolled in the dose escalation (8 AML and 7 NSCLC). ABBV-184 doses ranged from 0.07 mg/kg-0.7 µg/kg, with a half-life of approximately 13-29 hours. Transient cytokine increases were observed at all dose levels, and in patients with NSCLC, transient peripheral blood lymphocyte decreases were observed. The most frequently reported treatment-emergent adverse events (TEAEs) were anemia, diarrhea, and headache. Grade 1-2 infusion-related reaction (IRR) and cytokine release syndrome (CRS) TEAEs were reported.ABBV-184 was well tolerated and demonstrated preliminary evidence of CD3 engagement with transient cytokine increases and peripheral lymphocyte decreases.NCT04272203.