METHODS OF TREATING CNS TUMORS WITH TESETAXEL

1 . A method of treating a cancer in the central nervous system (CNS) of a human patient, comprising administering a therapeutically effective amount of tesetaxel systemically.

2 . The method of claim 1 , wherein the tesetaxel is administered orally.

3 . The method of claim 1 or 2 , wherein the cancer comprises a metastatic tumor.

4 . The method of claim 3 , wherein the metastatic tumor is a metastasis of a primary cancer selected from breast cancer.

5 . The method of claim 4 , wherein the breast cancer is hormone receptor positive.

6 . The method of any one of claims 4 - 5 , wherein the patient has previously received endocrine therapy.

7 . The method of any one of claims 4 - 6 , wherein the breast cancer is estrogen receptor positive.

8 . The method of any one of claims 4 - 7 , wherein the breast cancer is progesterone receptor positive.

9 . The method of any one of claims 4 - 8 , wherein the breast cancer is human epidermal growth factor receptor 2 (HER2) negative.

10 . The method of any one of claims 4 - 9 , wherein the breast cancer is hormone receptor positive and HER2-negative.

11 . The method of any of claim 4 , wherein the breast cancer is hormone receptor (HR) negative and HER2-negative.

12 . The method of claim 3 , wherein the metastatic tumor is a metastasis of a primary lung cancer, such as non-small cell lung cancer or small cell lung cancer.

13 . The method of claim 1 or 2 , wherein the cancer comprises a primary CNS tumor.

14 . The method of claim 13 , wherein the primary CNS tumor is an acoustic neuroma, astrocytoma, chordoma, CNS lymphoma, craniopharyngioma, glioma, medulloblastoma, meningioma, oligodendroglioma, pituitary tumor, primitive neuroectodermal or schwannoma.

15 . The method of any one of the preceding claims, comprising administering the tesetaxel on day 1 of a 21-day cycle.

16 . The method of any one of the preceding claims, further comprising administering a therapeutically effective amount of capecitabine.

17 . The method of claim 16 , comprising administering 14 daily doses of capecitabine starting on day 1 of the 21-day cycle.

18 . The method of any one of claims 15 - 17 , comprising repeating the 21-day cycle at least once.

19 . The method of claim 18 , comprising repeating the 21-day cycle until the cancer progresses or until unacceptable toxicity is observed.

20 . The method of any one of claims 15 - 18 , wherein administering a therapeutically effective amount of tesetaxel comprises administering 18-31 mg/m 2 of tesetaxel on day 1 of the 21-day cycle.

21 . The method of any one of claims 15 - 20 , wherein administering a therapeutically effective amount of tesetaxel comprises administering 27 mg/m 2 of tesetaxel on day 1 of the 21-day cycle.

22 . The method of any one of the preceding claims, further comprising administering a therapeutically effective amount of an inhibitor of programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1), such as nivolumab, pembrolizumab, or atezolizumab.

23 . The method of claim 22 , wherein the inhibitor of PD-1 or PD-L1 is administered on day 1 of a 21-day cycle.

24 . The method of claim 23 , wherein the inhibitor is administered by intravenous infusion.

25 . The method of claim 24 , wherein the intravenous infusion occurs over 30 minutes.

26 . The method of claim 24 , wherein the intravenous infusion occurs over 60 minutes.

27 . The method of any one of claims 16 - 26 , wherein administering a therapeutically effective amount of capecitabine comprises administering 14 daily doses of capecitabine at twice-daily intervals.

28 . The method of any one of claims 16 - 26 , wherein administering a therapeutically effective amount of capecitabine comprises administering capecitabine in 28 doses at twice-daily intervals beginning on day 1 of the 21-day cycle.

29 . The method of claim 28 , wherein administering a therapeutically effective amount of capecitabine comprises administering a first dose of capecitabine on day 1 of the 21-day cycle and administering a final 28 th dose on day 15 of the 21-day cycle.

30 . The method of any one of claims 16 - 29 , wherein administering a therapeutically effective amount of capecitabine comprises administering 14 daily doses of 300-2,000 mg/m 2 of capecitabine beginning on day 1 of the 21-day cycle.

31 . The method of any one of claims 16 - 30 , wherein administering a therapeutically effective amount of capecitabine comprises administering 14 daily doses of 1,650 mg/m 2 of capecitabine beginning on day 1 of the 21-day cycle.

32 . The method of claim 31 , wherein administering a therapeutically effective amount of capecitabine comprises administering 825 mg/m 2 of capecitabine at twice-daily intervals for 14 consecutive 24-hour periods beginning on day 1 of the 21-day cycle.

33 . The method of any one of claims 16 - 30 , wherein administering a therapeutically effective amount of capecitabine comprises administering 14 daily doses of 1,750 mg/m 2 of capecitabine beginning on day 1 of the 21-day cycle.

34 . The method of claim 33 , wherein administering a therapeutically effective amount of capecitabine comprises administering 875 mg/m 2 of capecitabine at twice-daily intervals for 14 consecutive 24-hour periods beginning on day 1 of the 21-day cycle.

35 . The method of any one of claims 16 - 30 , wherein administering a therapeutically effective amount of capecitabine comprises administering 28 doses of 150-1,000 mg/m 2 capecitabine at twice-daily intervals.

36 . The method of claim 35 , wherein administering a therapeutically effective amount of capecitabine comprises administering 28 doses of 150-1,000 mg/m 2 of capecitabine at twice-daily intervals beginning with the first dose on day 1 of the 21-day cycle and ending with the 28 th dose on day 15 of the 21-day cycle.

37 . The method of claim 35 , wherein administering a therapeutically effective amount of capecitabine comprises administering 28 doses of 825 mg/m 2 capecitabine at twice-daily intervals.

38 . The method of any one of claims 16 - 26 , wherein administering a therapeutically effective amount of capecitabine comprises administering 28 doses of 825 mg/m 2 of capecitabine at twice-daily intervals beginning with the first dose on day 1 of the 21-day cycle and ending with the 28 th dose on day 15 of the 21-day cycle.

39 . The method of claim 16 - 26 , wherein administering a therapeutically effective amount of capecitabine comprises administering 28 doses of 875 mg/m 2 capecitabine at twice-daily intervals.

40 . The method of claim 39 , wherein administering a therapeutically effective amount of capecitabine comprises administering 28 doses of 875 mg/m 2 of capecitabine at twice-daily intervals beginning with the first dose on day 1 of the 21-day cycle and ending with the 28 th dose on day 15 of the 21-day cycle.

41 . The method of any one of claims 1 - 40 , wherein the patient has previously been treated with a taxane.

42 . The method of any one of claims 1 - 40 , wherein the patient has not previously been treated with a taxane.

43 . The method of claim 41 , wherein the patient has previously been treated with a taxane in the neoadjuvant or adjuvant setting.

44 . The method of claim 41 or 43 , wherein the taxane is paclitaxel, docetaxel or albumin-bound paclitaxel.