Combination therapy comprising nivolumab and ipilimumab
This provides pharmaceutical compositions that comprise a combination of an anti-cancer agent which is an first antibody and a second antibody. In some embodiments, the first antibody is an anti-Programmed Death-1 (PD-1) antibody. In certain embodiments, the composition is a fixed dose formulation. In certain embodiments, the composition is administered as a flat-dose. The disclosure also provides a kit for treating a subject afflicted with a disease, the kit comprising a dosage of any composition disclosed herein and instructions for using the composition in any of the disclosed methods for treating a disease.
1. A method of treating a cancer in a patient in need thereof comprising administering to the patient a pharmaceutical composition comprising about 1.54 mg/ml nivolumab, about 4.62 mg/ml ipilimumab, about 18.46 mM Tris hydrochloride (HCl), about 1.54 mM sodium citrate dihydrate, about 1.15% mannitol, about 96.15 mM NaCl, about 93.85 pentetic acid, and about 0.012% PS80; wherein the cancer comprises a lung cancer, a metastatic melanoma, or a renal cell carcinoma.
2. The method of claim 1 , wherein the composition:
(i) is stable at about 5° C. for at least about 1 week;
(ii) is stable at about 40° C. for at least about 1 week; or
(iii) is stable at about 25° C. for at least about 1 week.
3. The method of claim 1 , wherein the pH of the composition is about 6.0, about 6.2, about 6.5, about 6.6, or about 7.0.
4. The method of claim 1 , wherein the pH of the composition is about 6.2.
5. The method of claim 1 , wherein the pH of the composition is 6.2.
6. The method of claim 1 , wherein the pH of the composition is 6.1.
7. The method of claim 1 , wherein the composition comprises 1.54 mg/mL nivolumab and 4.62 mg/ml ipilimumab.
8. The method of claim 1 , wherein the composition comprises about 30 mg nivolumab and about 90 mg ipilimumab.
9. The method of claim 1 , wherein the composition comprises about 40 mg nivolumab and about 120 mg ipilimumab.
10. The method of claim 1 , wherein the composition comprises 18.46 mM Tris hydrochloride (HCl).
11. The method of claim 1 , wherein the composition comprises 1.54 mM sodium citrate dihydrate.
12. The method of claim 1 , wherein the composition comprises 1.15% mannitol.
13. The method of claim 1 , wherein the composition comprises 96.15 mM NaCl.
14. The method of claim 1 , wherein the composition comprises 93.85 pentetic acid.
15. The method of claim 1 , wherein the composition comprises 0.012% PS80.
16. The method of claim 1 , wherein the composition comprises 18.46 mM Tris hydrochloride (HCl) and 1.54 mM sodium citrate dihydrate.
17. The method of claim 1 , wherein the composition comprises 1.15% mannitol, 96.15 mM NaCl, and 93.85 μM pentetic acid.
18. The method of claim 1 , wherein the composition comprises 18.46 mM Tris hydrochloride (HCl), 1.54 mM sodium citrate dihydrate, 1.15% mannitol, 96.15 mM NaCl, and 93.85 μM pentetic acid.
19. The method of claim 1 , wherein the composition comprises 18.46 mM Tris hydrochloride (HCl), 1.54 mM sodium citrate dihydrate, 1.15% mannitol, 96.15 mM NaCl, 93.85 μM pentetic acid, and 0.012% PS80.
20. The method of claim 19 , wherein the pH is 6.2 at 25° C.
21. The method of claim 1 , wherein the pH of the composition is between about 6.0 and about 7.0.
22. The method of claim 1 , wherein the composition:
(i) is stable at 5° C. for at least 1 week;
(ii) is stable at 40° C. for at least 1 week; or
(iii) is stable at 25° C. for at least 1 week.
23. A method of treating a cancer in a patient in need thereof comprising administering to the patient a pharmaceutical composition comprising 1.54 mg/ml nivolumab, 4.62 mg/ml ipilimumab, 18.46 mM Tris hydrochloride (HCl), 1.54 mM sodium citrate dihydrate, 1.15% mannitol, 96.15 mM NaCl, 93.85 μM pentetic acid, and 0.012% PS80; wherein the cancer comprises a lung cancer, a metastatic melanoma, or a renal cell carcinoma.
24. The method of claim 23 , wherein the pH of the composition is between about 6.0 and about 7.0.
25. The method of claim 23 , wherein the pH of the composition is 6.2 at 25° C.
26. The method of claim 23 , wherein the composition:
(i) is stable at 5° C. for at least 1 week;
(ii) is stable at 40° C. for at least 1 week; or
(iii) is stable at 25° C. for at least 1 week.
27. The method of claim 23 , wherein the composition comprises about 30 mg nivolumab and about 90 mg ipilimumab.
28. The method of claim 23 , wherein the composition comprises about 40 mg nivolumab and about 120 mg ipilimumab.
29. The method of claim 1 , wherein the lung cancer comprises non-small cell lung cancer (NSCLC).