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Preclinical discovery and initial clinical data of WVT078, a BCMA × CD3 bispecific antibody.

Abstract: 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.

 Fuente: Leukemia, 2023, 37, 1349-1360

 Editorial: Nature Publishing Group

 Año de publicación: 2023

 Nº de páginas: 12

 Tipo de publicación: Artículo de Revista

 DOI: 10.1038/s41375-023-01883-3

 ISSN: 0887-6924,1476-5551

 Url de la publicación: https://doi.org/10.1038/s41375-023-01883-3

Autoría

RAAB, MARC S.

COHEN, YAEL C.

SCHJESVOLD, FREDRIK

AARDALEN, KIMBERLY

OKA, ADWAIT

SPENCER, ANDREW

WERMKE, MARTIN

SOUZA, ANITA D.

KAUFMAN, JONATHAN L.

CAFRO, ANNA MARIA

HENSON, KRISTIN

TRABUCCO, GINA

CARRION, ANA

BENDER, FLORENT C.

JUIF, PIERRE-ERIC

FESSEHATSION, ADONAI

FAN, LIQUIONG

STONEHOUSE, JEFFREY P.