COMBINATION THERAPY
The invention generally relates to a combination therapy for treating cancer comprising administering at least two distinct therapeutic agents. Components of the combination therapy and methods of using the combination therapy are provided.
1 . A method of treating cancer of a subject, comprising administering: (A) a first component which comprises Component I, or a prodrug, derivative, or pharmaceutically-acceptable salt thereof; and (B) a second component which comprises Component II, or a prodrug, derivative, or a pharmaceutically-acceptable salt thereof, wherein
Component I is a conjugate comprising an active agent or prodrug thereof attached to a targeting moiety, wherein the active agent comprises a tubulin inhibitor or prodrug thereof; and
Component II is different from Component I.
2 . The method of claim 1 , wherein the targeting moiety of Component I binds to a somatostatin receptor (SSTR).
3 . The method of claim 2 , wherein the targeting moiety is selected from the group consisting of somatostatin, octreotide, seglitide, vapreotide, Tyr 3 -octreotate (TATE), cyclo(AA-Tyr-DTrp-Lys-Thr-Phe) where AA is α-N-Me lysine or N-Me glutamic acid, pasireotide, lanreotide, or analogs or derivatives thereof.
4 . (canceled)
5 . (canceled)
6 . The method of claim 1 , wherein Component I comprises TATE as the targeting moiety and DM1 as the active agent.
7 . The method of claim 1 , wherein Component I is Conjugate 1 having a structure of
8 . The method of claim 7 , wherein Conjugate 1 is administered in a pharmaceutical composition with a pH between about 4.0 to about 5.0.
9 . The method of claim 8 , wherein the pharmaceutical composition comprises acetate buffer.
10 . The method of claim 8 , wherein Conjugate 1 has a concentration of between about 2.0-about 5.0 mg/mL.
11 . The method of claim 8 , wherein the pharmaceutical composition further comprises mannitol.
12 . (canceled)
13 . The method of claim 8 , wherein the pharmaceutical composition further comprises polyoxyl 15 hydroxystearate.
14 . (canceled)
15 . (canceled)
16 . The method of claim 1 , wherein Component II is a checkpoint inhibitor.
17 . The method of claim 16 , wherein Component II comprises a CTLA-4 antagonist.
18 . The method of claim 16 , wherein Component II blocks the PD-1 and PD-L1/2 checkpoint pathway.
19 . The method of claim 18 , wherein Component II comprises a PD-1 antagonist or a PD-L1 antagonist.
20 . (canceled)
21 . The method of claim 1 , wherein Component II is an HDAC inhibitor.
22 . The method of claim 21 , wherein the HDAC inhibitor is vorinostat.
23 . The method of claim 1 , wherein Component II is octreotide or its derivative/analog.
24 . The method of claim 1 , wherein Component II comprises a radioactive agent.
25 . The method of claim 1 , wherein the subject further receives radiation therapy.
26 . The method of claim 1 , wherein Component II is a conjugate comprising an active agent or prodrug thereof attached to a targeting moiety, wherein the targeting moiety binds to heat shock protein 90 (HSP90).
27 . The method of claim 26 , wherein the targeting moiety of Component II is selected from the group consisting of ganetespib, geldanamycin, IPI-493, macbecins, tripterins, tanespimycins, 17-AAG, or a tautomer, analog, or derivative thereof.
28 . (canceled)
29 . The method of claim 26 , wherein the active agent of Component II is selected from the group consisting of SN-38, irinotecan, lenalidomide, vorinostat, 5-Fluorouracil (5-FU), abiraterone, bendamustine, crizotinib, doxorubicin, pemetrexed, fulvestrant, topotecan, Vascular Disrupting Agent (VDA), or a fragment, derivative, or analog thereof.
30 . The method of claim 26 , wherein Component II is Conjugate 2 having a structure of
or its tautomer.
31 . The method of claim 30 , wherein Conjugate 2 is administered in a pharmaceutical composition with a pH of above 8.0.
32 . The method of claim 31 , wherein Conjugate 2 is in its carboxylic acid salt form.
33 . The method of claim 31 , wherein the pharmaceutical composition further comprises sodium chloride.
34 . (canceled)
35 . The method of claim 1 , wherein Component I is Conjugate 1 and Component II is Conjugate 2.
36 . The method of claim 1 , wherein Component I is Conjugate 1 and Component II is vorinostat.
37 . The method of claim 36 , wherein vorinostat is administered before Conjugate 1.
38 . (canceled)
39 . (canceled)
40 . (canceled)
41 . The method of claim 1 , wherein the cancer is selected from a group consisting of lung cancer, breast cancer, colorectal cancer, ovarian cancer, pancreatic cancer, colorectal cancer, bladder cancer, prostate cancer, cervical cancer, renal cancer, leukemia, central nervous system cancers, myeloma, and melanoma.
42 . The method of claim 1 , wherein the cancer is a neuroendocrine cancer.
43 . The method of claim 1 , wherein the cancer is SSTR positive.
44 . The method of claim 1 , wherein the cancer is low in SSTR expression.