Methods for treating cancer and pharmaceutical compositions thereof

Abstract

1. A method of treating cancer in a subject comprising administering to the subject a bispecific antibody having binding specificities for EGFR and HER3 and a therapeutic agent, wherein the therapeutic agent comprises a tyrosine kinase inhibitor (TKI), an alkylating agent, an antimetabolite, a microtubule inhibitor, an anti-neoplastic antibiotic, a topoisomerase inhibitor, a chemoprotectant, or a combination thereof.

Claims

1. A pharmaceutical composition for treating a target cancer, comprising a bispecific antibody having binding specificity to EGFR and HER3, or a therapeutic agent, used in combination therapy of a bispecific antibody having binding specificity to EGFR and HER3 and a therapeutic agent, wherein the bispecific antibody comprises three complementarity-determining regions (CDRs) of SEQ ID NO: 1, six CDRs of SEQ ID NO: 2, and three CDRs of SEQ ID NO: 4, and the therapeutic agent is selected from the group consisting of osimertinib; a combination of paclitaxel and carboplatin; and a combination of cisplatin and pemetrexed.

2. The pharmaceutical composition according to claim 1, wherein the bispecific antibody comprises a heavy chain variable region (VH) having an amino acid sequence having at least 98% sequence identity with SEQ ID NO: 1, a heavy chain scFv domain having an amino acid sequence having at least 98% sequence identity with SEQ ID NO: 2, and a light chain variable region (VL) having an amino acid sequence having at least 98% sequence identity with SEQ ID NO:

4.

3. The pharmaceutical composition according to claim 1, wherein the bispecific antibody comprises a heavy chain and a light chain, the heavy chain comprising an amino acid sequence having at least 98% sequence identity with SEQ ID NO: 3, and the light chain comprising an amino acid sequence having at least 98% sequence identity with SEQ ID NO:

5.

4. The pharmaceutical composition according to claim 1, wherein in the combination therapy, the bispecific antibody and the therapeutic agent are administered simultaneously or sequentially as a single treatment session.

5. The pharmaceutical composition according to claim 1, wherein in the combination therapy, the bispecific antibody and the therapeutic agent are administered separately to the subject in alternating treatment sessions.

6. In the aforementioned combination therapy, the bispecific antibody is administered in the first treatment session, the therapeutic agent is administered in the second treatment session, the antibody is administered once a week (Q1W), once every two weeks (Q2W), once every three weeks (Q3W), or once a week for two weeks every three weeks (D1D8, Q3W), and the antibody is administered in a fixed dose, mg / kg dose, or mg / m² dose. 2 A pharmaceutical composition according to claim 1, administered in a specified dose.

7. The pharmaceutical composition according to claim 6, wherein the duration of the first treatment session is approximately 7 to approximately 728 days.

8. The pharmaceutical composition according to claim 6, wherein the duration of the second treatment session is approximately 1 to approximately 728 days.

9. The pharmaceutical composition according to claim 6, wherein the interval between the first treatment session and the second treatment session is about 7 to about 21 days.

10. The pharmaceutical composition according to claim 1, wherein in the combination therapy, the bispecific antibody is administered in doses of at least about 0.3 mg / kg, about 1.2 mg / kg, about 3.0 mg / kg, about 6.0 mg / kg, about 9.0 mg / kg, about 12.0 mg / kg, about 14.0 mg / kg, about 16.0 mg / kg, about 21.0 mg / kg, or about 28.0 mg / kg.

11. The pharmaceutical composition according to claim 1, wherein in the combination therapy, the therapeutic agent is administered in a dose of about 6.0 mg / kg to about 28.0 mg / kg.

12. The pharmaceutical composition according to claim 1, wherein the therapeutic agent is osimertinib, and in the combination therapy, the osimertinib is administered in a dose of at least about 40 mg / kg, about 80 mg / kg, about 120 mg / kg, or about 160 mg / kg.

13. The aforementioned therapeutic agent is a combination of paclitaxel and carboplatin, and in the aforementioned combination therapy, carboplatin is administered at a dose of at least approximately 200 mg / m². 2 , about 250 mg / m 2 , about 300 mg / m 2 , about 360 mg / m 2 , about 400 mg / m 2 The pharmaceutical composition according to claim 1, administered in a dose with an AUC of approximately 5 mg / ml / min, approximately 6 mg / ml / min, or approximately 7 mg / ml / min.

14. The therapeutic agent is a combination of cisplatin and pemetrexed, and in the combined treatment, cisplatin is administered at a dose of at least about 15 mg / m 2 , about 20 mg / m 2 , about 30 mg / m 2 , about 50 mg / m 2 , about 75 mg / m 2 , about 100 mg / m 2 , or about 120 mg / m 2 The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is administered at a dose of

15. The aforementioned therapeutic agent is a combination of cisplatin and pemetrexed, and in the aforementioned combination therapy, pemetrexed is administered at a dose of at least approximately 250 mg / m². 2 , about 500 mg / m 2 , or approximately 750 mg / m² 2 The pharmaceutical composition according to claim 1, administered in the dose of [amount].

16. The aforementioned therapeutic agent is a combination of paclitaxel and carboplatin, and in the aforementioned combination therapy, paclitaxel is at least about 40 mg / m². 2 , about 80 mg / m 2 , about 135 mg / m 2 , or approximately 175 mg / m² 2 The pharmaceutical composition according to claim 1, administered in the dose of [amount].

17. The pharmaceutical composition according to claim 1, wherein in the combination therapy, the bispecific antibody and the therapeutic agent are administered simultaneously and sequentially.

18. The pharmaceutical composition according to claim 1, wherein in the combination therapy, the bispecific antibody is administered at a time different from the therapeutic agent.

19. The pharmaceutical composition according to claim 1, wherein the cancer includes solid tumors that are positive for EGFR expression testing, and is selected from the group consisting of lung adenocarcinoma, head and neck squamous cell carcinoma, rectal cancer, colon cancer, lung squamous cell carcinoma, thyroid cancer, bladder cancer, melanoma, cervical cancer, prostate cancer, breast cancer, uterine / endometrial cancer, pancreatic cancer, ovarian cancer, and papillary renal cancer.

20. A pharmaceutical composition according to any one of claims 1 to 19, comprising the bispecific antibody.

21. A pharmaceutical composition according to any one of claims 1 to 19, comprising the therapeutic agent.

22. A cancer treatment composition comprising a combination of a bispecific antibody having binding specificity to EGFR and HER3 and a therapeutic agent, wherein the bispecific antibody comprises three complementarity-determining regions (CDRs) of SEQ ID NO: 1, six CDRs of SEQ ID NO: 2, and three CDRs of SEQ ID NO: 4, and the therapeutic agent is selected from the group consisting of osimertinib; a combination of paclitaxel and carboplatin; and a combination of cisplatin and pemetrexed.

23. The therapeutic composition according to claim 22, wherein the bispecific antibody and the therapeutic agent are in the form of a pharmaceutical formulation administered simultaneously, sequentially, or concurrently.

24. A kit for use in the treatment of cancer, comprising a first container, a second container, and an accompanying leaflet, The kit comprises: a first container comprising at least one dose of a first therapeutic composition comprising a bispecific antibody having binding specificity to EGFR and HER3; a second container comprising at least one dose of a second therapeutic composition comprising a therapeutic agent; and a package insert comprising instructions for treating a target cancer using the first and second therapeutic compositions; wherein the bispecific antibody comprises three complementarity-determining regions (CDRs) of SEQ ID NO: 1, six CDRs of SEQ ID NO: 2, and three CDRs of SEQ ID NO: 4; and the therapeutic agent being selected from the group consisting of osimertinib; a combination of paclitaxel and carboplatin; and a combination of cisplatin and pemetrexed.

25. The kit according to claim 24, wherein the instructions state that the first and second therapeutic compositions are intended for use in treating subjects having cancer that is positive for EGFR expression testing.

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