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5 Facts you should know about

Obrixtamig

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1

DLL3 is highly expressed in neuroendocrine cancers
DLL3 is commonly found on the surface of SCLC and other high-grade neuroendocrine tumors, with limited expression in most normal adult tissues — making it a selective investigational target.

2

Obrixtamig is a bispecific T-cell engager
One arm of the molecule binds DLL3 on tumor cells; the other binds CD3 on T cells — forming a direct bridge between the immune system and the cancer cell.

3

Designed to redirect immune cells
By simultaneously engaging DLL3 and CD3, obrixtamig is intended to bring T cells into close proximity with DLL3-expressing cancer cells and activate an immune response.

4

T-cell activation may trigger targeted tumor killing
Formation of an immune synapse may stimulate the release of cytotoxic molecules (perforin, granzymes) designed to destroy DLL3-positive tumor cells.

 

5

Multiple tumor types are under investigation
Clinical studies are evaluating obrixtamig in small cell lung cancer (SCLC), extrapulmonary neuroendocrine carcinomas (NECs), and pulmonary NECs including large cell neuroendocrine carcinoma (LCNEC).

References:
Saunders LR, Bankovich AJ, Anderson WC, et al. Sci Transl Med. DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor–initiating cells in vivo. Wermke M, Capdevila J, Morgensztern D, et al. J Clin Oncol. Phase I dose-escalation results for the delta-like ligand 3/CD3 IgG-like T-cell engager obrixtamig (BI 764532) in patients with DLL3+ small cell lung cancer or neuroendocrine carcinomas.Capdevila J, et al. J Clin Oncol. Efficacy and safety of the DLL3/CD3 T-cell engager obrixtamig in patients with extrapulmonary neuroendocrine carcinomas. Labrijn AF, Janmaat ML, Reichert JM, Parren PWHI. Nat Rev Drug Discov. Bispecific antibodies: a mechanistic review of the pipeline. Stinchcombe JC, Griffiths GM. Annu Rev Cell Dev Biol. Secretory mechanisms in cell-mediated cytotoxicity. ClinicalTrials.gov. Study of BI 764532 in DLL3-positive small cell lung cancer and neuroendocrine carcinoma (NCT04429087). Rudin CM, Pietanza MC, Bauer TM, et al. Clin Cancer Res. Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer. George J, Lim JS, Jang SJ, et al. Nature. Comprehensive genomic profiles of small cell lung cancer identify SOX2 as a frequently amplified gene and DLL3 as a therapeutic target.