Preclinical discovery and initial clinical data of WVT078, a BCMA × CD3 bispecific antibody.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
29
08
2022
accepted:
20
03
2023
revised:
16
03
2023
medline:
8
6
2023
pubmed:
7
4
2023
entrez:
6
4
2023
Statut:
ppublish
Résumé
B-cell maturation antigen (BCMA) is an ideal target in multiple myeloma (MM) due to highly specific expression in malignant plasma cells. BCMA-directed therapies including antibody drug conjugates, chimeric antigen receptor-T cells and bispecific antibodies (BsAbs) have shown high response rates in MM. WVT078 is an anti-BCMA× anti-CD3 BsAb that binds to BCMA with subnanomolar-affinity. It was selected based on potent T cell activation and anti-MM activity in preclinical models with favorable tolerability in cynomolgus monkey. In the ongoing first-in-human phase I dose-escalation study (NCT04123418), 33 patients received intravenous WVT078 once weekly at escalated dosing. At the active doses of 48-250 µg/kg tested to date (n = 26), the overall response rate (ORR) was 38.5% (90% CI: 22.6-56.4%) and the complete response rate (CRR, stringent complete response + complete response) was 11.5%, (90% CI: 3.2-27.2%). At the highest dose level tested, the ORR was 75% (3 of 4 patients). 26 (78.8%) patients reported at least one Grade ≥3 AE and 16 of these AEs were suspected to be drug related. 20 patients (60.6%) experienced cytokine release syndrome. WVT078 has an acceptable safety profile and shows preliminary evidence of clinical activity at doses tested to date.
Identifiants
pubmed: 37024520
doi: 10.1038/s41375-023-01883-3
pii: 10.1038/s41375-023-01883-3
doi:
Substances chimiques
B-Cell Maturation Antigen
0
Immunoconjugates
0
Antibodies, Bispecific
0
Banques de données
ClinicalTrials.gov
['NCT04123418']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1349-1360Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
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