Multispecific binding agents against cd40 and cd137 in therapy

The binding agent for use of any one of the preceding claims, wherein the suitable amount of the binding agent is about 0.04-2.5 mg/kg body weight or about 3-200 mg in total;

• and/or about 0.25×10−9-16.9×10−9 mol/kg body weight or about 20×10−9-1350×10−9 mol in total.

The binding agent for use of any one of the preceding claims, wherein the binding agent is administered systemically, preferably intravenously.

The binding agent for use of any one of the preceding claims, wherein the binding agent is a multispecific antibody, such as a bispecific antibody.

The binding agent for use of any one of the preceding claims, wherein the binding agent is in the format of a full-length antibody or an antibody fragment.

The binding agent for use of any one of the preceding claims, which comprises

• i) a first heavy chain and light chain comprising said antigen-binding region capable of binding to CD40, and
• ii) a second heavy chain and light chain comprising said antigen-binding region capable of binding CD137.

The binding agent for use of any one of the preceding claims, wherein said binding agent comprises

• i) a first heavy chain and light chain comprising said antigen-binding region capable of binding to CD40, the first heavy chain comprising a first heavy chain constant region and the first light chain comprising a first light chain constant region;
• and
• ii) a second heavy chain and light chain comprising said antigen-binding region capable of binding CD137, the second heavy chain comprising a second heavy chain constant region and the second light chain comprising a second light chain constant region.

The binding agent for use of any of the preceding claims, wherein said binding agent induces Fc-mediated effector function to a lesser extent compared to another antibody comprising the same first and second antigen binding regions and two heavy chain constant regions (CHs) comprising human IgG1 hinge, CH2 and CH3 regions.

The binding agent for use of any one of the preceding claims, wherein said binding agent comprises a kappa (κ) light chain constant region.

The binding agent for use of any one of the preceding claims, wherein said binding agent comprises a lambda (λ) light chain constant region.

The binding agent for use of any one of the preceding claims, wherein said first light chain constant region is a kappa (κ) light chain constant region or a lambda (λ) light chain constant region.

The binding agent for use of any one of the preceding claims, wherein said second light chain constant region is a lambda (λ) light chain constant region or a kappa (κ) light chain constant region.

The binding agent for use of any one of the preceding claims, wherein said first light chain constant region is a kappa (κ) light chain constant region and said second light chain constant region is a lambda (λ) light chain constant region or said first light chain constant region is a lambda (λ) light chain constant region and said second light chain constant region is a kappa (κ) light chain constant region.

The binding agent for use of any one of the preceding claims, wherein the binding agent is of an isotype selected from the group consisting of IgG1, IgG2, IgG3, and IgG4.

The binding agent for use of any one of the preceding claims, wherein the binding agent is a full-length IgG1 antibody.

The binding agent for use of any one of the preceding claims, wherein the binding agent is an antibody of the IgG1m(f) allotype.

The binding agent for use of any one of the preceding claims, wherein the subject is a human subject.

The binding agent for use of any one of the preceding claims, wherein the tumor or cancer is a solid tumor.

The binding agent for use of any one of the preceding claims, wherein the tumor or cancer is selected from the group consisting of melanoma, ovarian cancer, lung cancer (e.g., non-small cell lung cancer (NSCLC)), colorectal cancer, head and neck cancer, gastric cancer, breast cancer, renal cancer, urothelial cancer, bladder cancer, esophageal cancer, pancreatic cancer, hepatic cancer, thymoma and thymic carcinoma, brain cancer, glioma, adrenocortical carcinoma, thyroid cancer, other skin cancers, sarcoma, multiple myeloma, leukemia, lymphoma, myelodysplastic syndromes, ovarian cancer, endometrial cancer, prostate cancer, penile cancer, cervical cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, Merkel cell carcinoma and mesothelioma.

The binding agent for use of any one of the preceding claims, wherein the tumor or cancer is selected from the group consisting of lung cancer (e.g., non-small cell lung cancer (NSCLC)), melanoma, colorectal cancer, urothelial cancer (cancer of the bladder, ureter, urethra, or renal pelvis), endometrial cancer (EC), breast cancer (e.g., triple negative breast cancer (TNBC)), squamous cell carcinoma of the head and neck (SCCHN) (e.g., cancer of the oral cavity, pharynx or larynx) and cervical cancer.

The binding agent for use of any one of the preceding claims, wherein the tumor or cancer is selected from the group consisting of lung cancer, melanoma, and colorectal cancer.

The binding agent for use of any one of the preceding claims, wherein the binding agent is administered in at least one treatment cycle, each treatment cycle being three weeks (21 days).

The binding agent for use of any one of the preceding claims, wherein one dose is administered every third week (1Q3W).

The binding agent for use of any one of the preceding claims, wherein one dose is administered on day 1 of each treatment cycle.

The binding agent for use of any one of the preceding claims, wherein each dose is infused over a minimum of 30 minutes, such as over a minimum of 60 minutes, a minimum of 90 minutes, a minimum of 120 minutes or a minimum of 240 minutes.

A composition comprising a binding agent comprising a first binding region binding to human CD40 and a second binding region binding to human CD137, wherein the amount of binding agent in the composition is between about 3-200 mg or about 20×10−9-1350×10−9 mol.