Use of t-cell engaging proteins in the treatment of cancer

The T-cell engaging protein for use according to any of the preceding claims, comprising the step of determining or having determined that the subject exhibits at least a threshold of DLL3-positivity.

The T-cell engaging protein for use according to any of the preceding claims, wherein the threshold is at least about 10%, at least about 20% at least about 25%, at least about 30%, at least about 40%, at least about 50% or at least about 75%.

The T-cell engaging protein for use according to any of the preceding claims, wherein the threshold is at least about 25%, at least about 50%, or at least about 75%.

The T-cell engaging protein for use according to any one of the proceeding claims, wherein DLL3 positivity is determined using an immunohistochemical (IHC) assay.

The T-cell engaging protein for use according to any one of the proceeding claims, wherein DLL3 positivity is determined in a tissue sample from the subject, preferably in a formalin fixed paraffin embedded (FFPE) tissue sample.

The T-cell engaging protein for use according to any one of the preceding claims, wherein said Neuroendocrine Neoplasm (NEN) is a Neuroendocrine Carcinoma (NEC), preferably selected from the group consisting of Lung-NEC such as LCNEC of the lung, Extrapulmonary (ep) NEC including NEC with unknown primary site;

• small cell lung cancer (SCLC) including extensive-stage (ES)-SCLC, and limited-stage (LS) SCLC;
• or said NEN is a Neuroendocrine Tumor (NET) such as grade 3 NET.

The T-cell engaging protein for use according to any one of the preceding claims, wherein at least one further anti-cancer agent is to be administered, said further anti-cancer agent preferably being a chemotherapeutic agent and/or an immune-checkpoint inhibitor such as an anti-PD-1 antibody or an anti-PD-L1 antibody.

A method for selecting a subject suffering from a DLL3-positive cancer or a cancer selected from a Neuroendocrine Neoplasm (NEN), Merkel cell carcinoma (MCC), medullary thyroidal carcinoma and glioma for treatment with a T-cell engaging protein comprising a first antigen binding unit specifically binding to DLL3 and a second antigen binding unit specifically binding to CD3, the method comprising:

• (a) determining or having determined in a sample that the subject exhibits DLL3 positivity, wherein the subject is selected for treatment with said T-cell engaging protein when the DLL3-positivity exhibits at least a threshold, and
• wherein said T-cell engaging protein comprises a first antigen binding unit specifically binding to DLL3, comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:13 (CDR1), SEQ ID NO:14 (CDR2) and SEQ ID NO:15 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:16 (CDR1), SEQ ID NO:17 (CDR2) and SEQ ID NO:18 (CDR3) and a second antigen binding unit specifically binding to CD3 comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:55 (CDR1), SEQ ID NO:56 (CDR2) and SEQ ID NO:57 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:58 (CDR1), SEQ ID NO:59 (CDR2) and SEQ ID NO:60 (CDR3).