Combination therapy of MDNA55 and a vascular endothelial growth factor a (VEGF-A)
Methods for treating a central nervous system (CNS) tumor in a subject, comprising administering to the subject MD-NA55 in combination with a vascular endothelial growth factor A (VEGF-A) inhibitor administered at a subtherapeutic level.
1 . A method of treating a central nervous system (CNS) tumor in a subject, comprising administering to the subject MDNA55 (SEQ ID NO: 1) in combination with a vascular endothelial growth factor A (VEGF-A) inhibitor administered at a subtherapeutic level,
wherein the VEGF-A inhibitor is administered at least two weeks apart from the MDNA55;
wherein the VEGF-A inhibitor is bevacizumab or a biosimilar of bevacizumab; and
wherein the CNS tumor is an IL-4 receptor (IL-4R)-positive CNS tumor.
2 . A method of inhibiting a central nervous system (CNS) tumor in a subject that is characterized by IL-4 receptor (IL-4R) expression, comprising:
a) contacting the CNS tumor with MDNA55 (SEQ ID NO: 1); and
b) contacting the CNS tumor with a subtherapeutic level of a vascular endothelial growth factor A (VEGF-A) inhibitor at least two weeks apart from the contact with the MDNA55,
wherein the VEGF-A inhibitor is bevacizumab or a biosimilar of bevacizumab.
3 . The method according to claim 1 , wherein the CNS tumor is a recurrent CNS tumor or a newly diagnosed CNS tumor.
4 . The method according to claim 3 , wherein the CNS tumor is a recurrent or refractory glioblastoma.
5 . The method according to claim 1 , wherein the CNS tumor is selected from the group consisting of glioma, glioblastoma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglia, meningioma, meningioma, neuroblastoma, and retinoblastoma.
6 . The method according to claim 1 , wherein the MDNA55 is administered as a single dose of about 90 μg, about 180 μg, or about 240 μg.
7 . The method according to claim 6 , wherein the MDNA55 is administered as a single dose of about 1.5 μg/mL in 60 mL, about 4.5 μg/mL in 40 mL or 3 μg/mL in 60 mL, or about 6 μg/mL in 40 mL or 4 μg/mL in 60 mL.
8 . The method according to claim 1 , wherein the MDNA55 is formulated in an artificial cerebral spinal fluid (CSF) solution and albumin.
9 . The method according to claim 1 , wherein the MDNA55 is administered intratumorally.
10 . The method according to claim 9 , wherein the intratumoral administration comprises intracranial administration.
11 . The method according to claim 1 , wherein the MDNA55 is administered via an intracranial catheter or by convection-enhanced delivery (CED), optionally wherein the MDNA55 is administered via one or more intracranial catheters.
12 . The method according to claim 11 , wherein the MDNA55 is administered through the catheter with a flow rate of about 5 μL/min/catheter to about 20 μL/min/catheter or a flow rate of about 15 μL/min/catheter.
13 . The method according to claim 1 , wherein the biosimilar of bevacizumab is selected from bevacizumab-awwb, bevacizumab-bvzr, Aybintio, MYL-14020, FKB238, BCD-021, BCD500, Krabeva, BAT1706, BI 695502, CT-P16, CHS-5217, DRZ_BZ, Lumiere, Cizumab, IBI-305, MIL60, Bevax, ONS-1045, HD204, Bevacirel, HLX04, and TX16.
14 . The method according to claim 1 , wherein the subtherapeutic dose of the VEGF-A inhibitor is below 10 mg/kg, or from 1 mg/kg to 7.5 mg/kg.
15 . The method according to claim 1 , wherein the VEGF-A inhibitor is administered after the MDNA55.
16 . The method according to claim 1 , wherein the VEGF-A inhibitor is administered before the MDNA55.
17 . The method according to claim 1 , wherein the VEGF-A inhibitor is administered at least two weeks apart from the MDNA55 for a period of at least 12 weeks, 16 weeks, 20 weeks, 24 weeks, 30 weeks, 36 weeks, 40 weeks, 44 weeks, 48 weeks, 52 weeks or more.