Quinoline derivative for treatment of nasopharyngeal carcinoma

1. A method for treating advanced and/or metastatic and/or recurrent nasopharyngeal carcinoma in a subject, the method comprising administering a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof to the subject in need thereof,

2. The method of claim 1 , wherein the nasopharyngeal carcinoma is keratinizing squamous cell carcinoma or non-keratinizing nasopharyngeal carcinoma.

3. The method of claim 2 , wherein the non-keratinizing nasopharyngeal carcinoma is differentiated or undifferentiated type.

4. The method of claim 1 , wherein the nasopharyngeal carcinoma is nasopharyngeal carcinoma in situ or infiltrating nasopharyngeal carcinoma.

5. The method of claim 4 , wherein the infiltrating nasopharyngeal carcinoma is squamous cell carcinoma, adenocarcinoma, microinvasive carcinoma, vesicular nucleus cell carcinoma, or undifferentiated nasopharyngeal carcinoma.

6. The method of claim 1 , wherein the nasopharyngeal carcinoma is advanced and/or metastatic nasopharyngeal carcinoma.

7. The method of claim 6 , wherein the subject has been treated with chemotherapy drug, monoclonal antibody, and/or radiotherapy.

8. The method of claim 1 , wherein the pharmaceutically acceptable salt of the compound of Formula (I) is a salt formed by the compound of Formula (I) with an acid selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, acetic acid, trifluoroacetic acid, propionic acid, caproic acid, heptanoic acid, cyclopentane propionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methyl sulfonic acid, ethyl sulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulphonic acid, benzenesulfonic acid, p-chlorobenzenesulfonic acid, p-toluenesulfonic acid, 3-phenylpropionic acid, trimethylacetic acid, t-butylacetic acid, dodecyl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, and stearic acid.

9. The method of claim 8 , wherein the pharmaceutically acceptable salt of the compound of Formula (I) is a hydrochloride salt.

10. The method of claim 1 , wherein the daily dose of the compound of Formula (I) or the pharmaceutically acceptable salt administered is selected from the group consisting of 2 mg to 20 mg, 5 mg to 20 mg, 10 mg to 16 mg, 10 mg to 14 mg, 8 mg, 10 mg, 12 mg, 14 mg, and 16 mg.

11. The method of claim 1 , wherein the compound of Formula (I) or a pharmaceutically acceptable salt thereof is administered by an interval administration regimen including administration periods and rest periods, and the ratio of the administration period to the rest period in days is 2:0.5-5, 2:0.5˜3, 2:0.5˜2, or 2:0.5˜1.

12. The method of claim 1 , wherein a compound of Formula (I) or the pharmaceutically acceptable salt thereof is administered by an interval administration regimen with a 14-day administration period and followed by a 7-day rest period.

13. The method of claim 1 , which further comprises administering to the subject another antitumor drug simultaneously or sequentially.

14. The method of claim 13 , wherein the another antitumor drug is selected from the group consisting of an alkylating agent, a platinum complex, a fluoropyrimidine derivative, camptothecin and a derivative thereof, anthraquinone antitumor antibiotic, taxane, and a monoclonal antibody.

15. A method for treating advanced and/or metastatic and/or recurrent nasopharyngeal carcinoma in a subject, the method comprising administering to the subject in need thereof an effective amount of a combined pharmaceutical composition comprising (i) a compound of Formula (I) or a pharmaceutically acceptable salt thereof; and (ii) at least one second therapeutic agent,

16. The method of claim 15 , wherein the combined pharmaceutical composition comprises:

(i) a pharmaceutical composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof and (ii) a pharmaceutical composition comprising at least one second therapeutic agent.

17. The method of claim 15 , wherein the second therapeutic agent is a chemotherapy drug, a small molecular targeted antitumor drug, an immunotherapy drug, or a macromolecular antibody.

18. The method of claim 17 , wherein the chemotherapy drug is selected from the group consisting of a platinum complex, fluoropyrimidine derivative, camptothecin and a derivative thereof, taxane, vinblastine and a derivative thereof, anthraquinone, antibiotic antitumor drug, podophyllum-based compound, antimetabolite antitumor drug, and a combination thereof.

19. The method of claim 17 , wherein the macromolecular antibody is selected from the group consisting of nivolumab, pembrolizumab, durvalumab, and toripalimab, centilimab, carrelizumab, tirelizumab, AK105, genolimzumab, livuzumab, HLX-10, BAT-1306, AK103, AK104, CS1003, SCT-I10A, F520, SG001, and GLS-010, and a combination thereof.

20. The method of claim 15 , wherein the combined pharmaceutical composition comprises one of the following:

(a) the compound of Formula (I) or pharmaceutically acceptable salt thereof, a platinum complex, and optionally combined with radiotherapy;

(b) the compound of Formula (I) or pharmaceutically acceptable salt thereof, a platinum complex, and Cetuximab, and optionally combined with radiotherapy;

(c) the compound of Formula (I) or pharmaceutically acceptable salt thereof, a platinum complex, and gemcitabine, and optionally combined with radiotherapy; and

(d) the compound of Formula (I) or pharmaceutically acceptable salt thereof, gemcitabine, paclitaxel, and optionally combined with radiotherapy.

21. The method of claim 1 , wherein the method for treating recurrent nasopharyngeal carcinoma.

22. The method of claim 15 , wherein the method for treating recurrent nasopharyngeal carcinoma.