Ifinatamab Deruxtecan and B7-H3 in SCLC

Author(s):

Panelists discuss how the overexpression of B7-H3 plays a crucial prognostic role in small cell lung cancer, exploring the mechanisms by which ifinatamab deruxtecan targets this protein to overcome treatment resistance and enhance tumor selectivity, while also considering the potential for durable responses and the use of patient-derived xenograft models to advance drug development and assess B7-H3 expression.

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EP: 7.Adverse Event Management: CRS and ICANS with Tarlatamab

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EP: 9.Ifinatamab Deruxtecan and B7-H3 in SCLC

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Video content above is prompted by the following:

1. Dr Leal: Please provide an overview of the prognostic importance of overexpression of the B7-H3 (CD276) transmembrane immunoregulatory protein, which promotes protumorigenic functions in patients with small cell lung cancer (SCLC).

What unique mechanisms of action demonstrate the potential of ifinatamab deruxtecan to target B7-H3, a cell surface, immune checkpoint protein, for the treatment of extensive-stage (ES) SCLC that has relapsed after 1 or more prior lines of therapy, including platinum-based chemotherapy and immunotherapy?
How might ifinatamab deruxtecan address PD-L1 acquired resistance during treatment of ES-SCLC?
What properties of ifinatamab deruxtecan enhance selective tumor cell death, facilitate a bystander effect, and reduce systemic drug exposure?

2. Dr Iams: Please share your perceptions of the potential for durable response to ifinatamab deruxtecan in patients with previously treated, relapsed SCLC.

As reported in the phase I/II clinical trial, how encouraging was an ORR[RP1] of 52.4%,

a 5.9-month median duration of response, and a 12.2-month overall survival in the 21 patients with relapsed SCLC following a median 2 (range 1-9) prior lines of therapy?

3. Dr Sen: Currently, are we able to assay B7-H3 to determine individual expression levels?