Expert review of anticancer therapy · 2024
First-in-human clinical trial results with ABBV-184, a first-in-class T-cell receptor/anti-CD3 bispecific protein, in adults with previously treated AML or NSCLC.
СтатьяКлиническое исследование I фазыМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Peterlin Pierre, Saada-Bouzid Esma, Moskovitz Mor, Pigneux Arnaud, Yuda Junichiro, Sinnollareddy Mahipal, Henner William R, Chen Diana, Freise Kevin J, Leibman Rachel S, Avigdor Abraham, Shimizu Toshio
Аннотация
BACKGROUND: 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).
RESEARCH DESIGN AND METHODS: 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.
RESULTS: 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.
CONCLUSIONS: ABBV-184 was well tolerated and demonstrated preliminary evidence of CD3 engagement with transient cytokine increases and peripheral lymphocyte decreases.
CLINICAL TRIAL REGISTRATION: NCT04272203.
RESEARCH DESIGN AND METHODS: 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.
RESULTS: 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.
CONCLUSIONS: ABBV-184 was well tolerated and demonstrated preliminary evidence of CD3 engagement with transient cytokine increases and peripheral lymphocyte decreases.
CLINICAL TRIAL REGISTRATION: NCT04272203.