Combination therapy using MEK inhibitors for cancer treatment

Abstract

The present invention relates to a combination of Omomyc or a functionally equivalent variant thereof, a conjugate comprising Omomyc or a functionally equivalent variant thereof, a polynucleotide encoding the polypeptide, a vector comprising the polynucleotide, and a cell capable of secreting the polypeptide or the conjugate, and a MEK inhibitor. The present invention also relates to a pharmaceutical composition comprising the combination of the present invention, and its medical use, in particular, its use in the treatment of cancer.

Claims

1. i) The group consisting of the following: a) A polypeptide comprising the sequence of Sequence ID No. 1 or a functionally equivalent variant thereof, b) A conjugate comprising a polypeptide containing the sequence of SEQ ID NO: 1 or a functionally equivalent variant thereof, and a chemical moiety that promotes intracellular uptake of the polypeptide or a functionally equivalent variant thereof. c) Polynucleotides encoding the polypeptide of a) or the conjugate of b), d) A vector containing the polynucleotides of c), and e) Cells that can secrete the polypeptide of a) or the conjugate of b) into the culture medium. A first component selected from, ii) The second component is a MEK inhibitor and A combination that includes [something].

2. The combination according to claim 1, wherein the first component is a polypeptide containing the sequence of sequence number 1.

3. The combination according to claim 1, wherein a functionally equivalent variant of Sequence ID No. 1 is selected from the group consisting of Sequence ID No. 4, Sequence ID No. 5, Sequence ID No. 6, Sequence ID No. 7, Sequence ID No. 8, Sequence ID No. 9, and Sequence ID No.

10.

4. The combination according to any one of claims 1 or 3, wherein the chemical portion that promotes intracellular uptake of the polypeptide or a functionally equivalent modified thereof is a cell membrane permeable peptide sequence, and further, the cell membrane permeable peptide sequence and the polypeptide or a functionally equivalent modified thereof form a fusion protein.

5. The combination according to any one of claims 1 or 3 to 4, wherein the conjugate further comprises a further nuclear localization signal.

6. The combination according to any one of claims 1 to 5, wherein the MEK inhibitor is selected from the group consisting of trametinib, pimacertib, and selumetinib.

7. The combination according to claim 6, wherein the MEK inhibitor is trametinib.

8. A pharmaceutical composition comprising a pharmaceutically effective amount of the combination described in any one of claims 1 to 7 and a pharmaceutically acceptable excipient.

9. A combination according to any one of claims 1 to 7 or a pharmaceutical composition according to claim 8, for use in medical settings.

10. A combination according to any one of claims 1 to 7 or a pharmaceutical composition according to claim 8 for use in the prevention and / or treatment of cancer.

11. The combination or pharmaceutical composition for use according to claim 10, wherein the cancer is selected from the group consisting of melanoma, colorectal cancer, and breast cancer.

12. The combination or pharmaceutical composition for use according to claim 11, wherein the cancer is melanoma.

13. The combination or pharmaceutical composition for use according to any one of claims 10 to 12, wherein the cancer is a cancer having a BRAF mutation.

14. The combination or pharmaceutical composition for use according to any one of claims 10 to 13, wherein the cancer is a cancer resistant to MEK inhibitors.

15. A combination or pharmaceutical composition for use according to any one of claims 9 to 14, wherein the first component is administered intravenously and the second component is administered orally.

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