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.
Expert Rev Anticancer Ther
; 24(9): 893-904, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-38946484
ABSTRACT
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-A201-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 ANDMETHODS:
This phase 1 multicenter, open-label, dose escalation trial (NCT04272203) enrolled adult patients with relapsed/refractory AML or NSCLC with an HLA-A201 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Antigen, T-Cell
/
Leukemia, Myeloid, Acute
/
CD3 Complex
/
Antibodies, Bispecific
/
Carcinoma, Non-Small-Cell Lung
/
Dose-Response Relationship, Drug
/
Lung Neoplasms
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Expert Rev Anticancer Ther
Journal subject:
NEOPLASIAS
/
TERAPEUTICA
Year:
2024
Document type:
Article
Affiliation country: