Abstract：
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: ABBV-184 was well tolerated and demonstrated preliminary evidence of CD3 engagement with transient cytokine increases and peripheral lymphocyte decreases.
UNASSIGNED: NCT04272203.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: ABBV-184 was well tolerated and demonstrated preliminary evidence of CD3 engagement with transient cytokine increases and peripheral lymphocyte decreases.
UNASSIGNED: NCT04272203.
摘要：
■ABBV-184，一种新型的存活蛋白肽靶向T细胞受体（TCR）/抗CD3双特异性蛋白，证明了临床前T细胞活化和对HLA-A2：01阳性肿瘤系的细胞毒性。这项首次人体试验评估了ABBV-184单药治疗急性髓细胞性白血病（AML）和非小细胞肺癌（NSCLC）患者的疗效。
■这个阶段1多中心，开放标签，剂量递增试验(NCT04272203)纳入了具有HLA-A2:01限制性基因型的复发性/难治性AML或NSCLC的成年患者.患者最初接受0.07ug/kg的ABBV-184，2至3倍剂量增加。主要目标是确定ABBV-184推荐的2期剂量。次要目标包括安全，耐受性,药代动力学，和免疫原性评估。
■15例患者参加剂量递增（8例AML和7例NSCLC）。ABBV-184剂量范围为0.07mg/kg-0.7µg/kg，半衰期约为13-29小时。在所有剂量水平观察到短暂的细胞因子增加，在NSCLC患者中，观察到短暂的外周血淋巴细胞减少。最常报告的治疗紧急不良事件（TEAE）是贫血，腹泻,和头痛。报告1-2级输注相关反应(IRR)和细胞因子释放综合征(CRS)TEAE。
■ABBV-184具有良好的耐受性，并显示了CD3参与短暂细胞因子增加和外周淋巴细胞减少的初步证据。
■NCT04272203。
■这个阶段1多中心，开放标签，剂量递增试验(NCT04272203)纳入了具有HLA-A2:01限制性基因型的复发性/难治性AML或NSCLC的成年患者.患者最初接受0.07ug/kg的ABBV-184，2至3倍剂量增加。主要目标是确定ABBV-184推荐的2期剂量。次要目标包括安全，耐受性,药代动力学，和免疫原性评估。
■15例患者参加剂量递增（8例AML和7例NSCLC）。ABBV-184剂量范围为0.07mg/kg-0.7µg/kg，半衰期约为13-29小时。在所有剂量水平观察到短暂的细胞因子增加，在NSCLC患者中，观察到短暂的外周血淋巴细胞减少。最常报告的治疗紧急不良事件（TEAE）是贫血，腹泻,和头痛。报告1-2级输注相关反应(IRR)和细胞因子释放综合征(CRS)TEAE。
■ABBV-184具有良好的耐受性，并显示了CD3参与短暂细胞因子增加和外周淋巴细胞减少的初步证据。
■NCT04272203。
