TREATMENT OF LUNG CANCER USING A COMBINATION OF AN ANTI-PD-1 ANTIBODY AND ANOTHER ANTI-CANCER AGENT

• US 20170158776A1
• Filed: 05/15/2015
• Published: 06/08/2017
• Est. Priority Date: 05/15/2014
• Status: Abandoned Application

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: FELTQUATE, David, CHEN, Allen C.
• Application Number:
  US15/311,409
• Publication Number:
  US 20170158776A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55 characterised by the host/recipient, e.g. newborn with maternal antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/282 Platinum compounds
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 16/3023 : Lung
• CPC Class Codes: C07K 16/32 : against translation products of oncogenes
• CPC Class Codes: C07K 2317/21 : from primates, e.g. man
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

This disclosure provides a method for treating a subject afflicted with a lung cancer, which method comprises administering to the subject therapeutically effective amounts of: (a) an anti-cancer agent which is an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity; and (b) another anti-cancer agent. The other anti-cancer agent can be a platinum-based doublet chemotherapy, an EGFR-targeted tyrosine kinase inhibitor, bevacizumab, an anti-Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) antibody, or any other therapy used to treat lung cancer in the art or disclosed herein.

Claims

1. A method for treating a subject afflicted with a lung cancer comprising administering to the subject a combination of therapeutically effective amounts of:

(a) an anti-cancer agent which is an antibody or an antigen-binding portion thereof that binds specifically to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity (“

an anti-PD-1 antibody or antigen-binding portion thereof”

); and

(b) another anti-cancer agent.

2. The method of claim 1, wherein the lung cancer is non-small cell lung cancer (NSCLC).

5. The method of claim 1, wherein the anti-PD-1 antibody or antigen-binding portion thereof cross-competes with nivolumab for binding to human PD-1.

8. The method of claim 1, wherein the anti-PD-1 antibody is nivolumab or pembrolizumab.

10. The method of claim 1, wherein the other anti-cancer agent is selected from:

a platinum-based doublet chemotherapy (PT-DC), an EGFR-targeted tyrosine kinase inhibitor (TKI), bevacizumab, and an antibody or an antigen-binding portion thereof that binds specifically to Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) and inhibits CTLA-4 activity (“

an anti-CTLA-4 antibody or antigen-binding portion thereof”

).

11. The method of claim 10, wherein the anti-PD-1 antibody or antigen-binding portion thereof is administered at (i) a dose ranging from 0.1 mg/kg to 10.0 mg/kg body weight once every 2, 3 or 4 weeks, or (ii) a dose of 5 mg/kg or 10 mg/kg body weight once every 3 weeks.

13. The method of claim 10, wherein the PT-DC was administered concurrently with the anti-PD-1 antibody or antigen-binding portion thereof for 4 doses of the anti-PD-1 antibody or antigen-binding portion thereof, followed by repeated administration of the anti-PD-1 antibody or antigen-binding portion thereof alone.

14. The method of claim 13, wherein the PT-DC is (i) a combination of gemcitabine and cisplatin;

(ii) a combination of pemetrexed and cisplatin;

or (iii) a combination of paclitaxel and carboplatin.

15. The method of claim 14, wherein (i) gemcitabine is administered at a dose of 1250 mg/m² in combination with cisplatin administered at a dose of 75 mg/m², (ii) pemetrexed is administered at a dose of 500 mg/m² in combination with cisplatin administered at a dose of 75 mg/m²;

or (iii) paclitaxel is administered at a dose of 200 mg/m² in combination with carboplatin administered at a target area under the curve of 6 mg/mL/min dose (AUC6).

21. The method of claim 10, wherein the EGFR-targeted TKI is erlotinib.

22. The method of claim 21, wherein the erlotinib is orally administered at a dose of 150 mg daily.

23. The method of claim 22, wherein the anti-PD-1 antibody or antigen-binding portion thereof is administered at a dose of 3 mg/kg body weight once every 2 weeks.

26. The method of claim 10, wherein the bevacizumab is intravenously administered at a dose of 15 mg/kg once every 3 weeks.

27. The method of claim 26, wherein the anti-PD-1 antibody or antigen-binding portion thereof is administered at a dose of 5 mg/kg body weight once every 3 weeks or at a dose of 3 mg/kg body weight once every 2 weeks.

31. The method of claim 10, wherein the anti-CTLA-4 antibody or antigen-binding portion thereof cross-competes with ipilimumab for binding to human CTLA-4.

34. The method of claim 10, wherein the anti-CTLA-4 antibody is ipilimumab or tremelimumab.

36. The method of claim 10, comprising:

(a) an induction phase, wherein the anti-PD-1 antibody or antigen-binding portion thereof and the anti-CTLA-4 antibody or antigen-binding portion thereof are administered in combination in 2, 4, 6, 8, or 10 doses, each dose ranging from 0.1 mg/kg to 10.0 mg/kg body weight administered at least once every 2, 3, or 4 weeks;

followed by

(b) a maintenance phase, wherein no anti-CTLA-4 antibody or antigen-binding portion thereof is administered and the anti-PD-1 antibody or antigen-binding portion thereof is repeatedly administered at a dose ranging from 0.1 mg/kg to 10 mg/kg at least once every 2, 3, or 4 weeks.

37. The method of claim 36, wherein:

(a) the induction phase comprises 4 combination doses administered at 3-week intervals, wherein;

(i) the anti-PD-1 antibody or antigen-binding portion thereof is administered at 3 mg/kg body weight and the anti-CTLA-4 antibody or antigen-binding portion thereof is administered at 1 mg/kg body weight;

(ii) the anti-PD-1 antibody or antigen-binding portion thereof is administered at 1 mg/kg body weight and the anti-CTLA-4 antibody or antigen-binding portion thereof is administered at 3 mg/kg body weight;

(iii) the anti-PD-1 antibody or antigen-binding portion thereof is administered at 1 mg/kg body weight and the anti-CTLA-4 antibody or antigen-binding portion thereof is administered at 1 mg/kg body weight;

or

(iv) the anti-PD-1 antibody or antigen-binding portion thereof is administered at 3 mg/kg body weight and the anti-CTLA-4 antibody or antigen-binding portion thereof is administered at 3 mg/kg body weight; and

(b) the maintenance phase comprises repeated administration of the anti-PD-1 antibody or antigen-binding portion thereof at a dose of 3 mg/kg every 2 weeks for as long as clinical benefit is observed or until unmanageable toxicity or disease progression occurs.

41. The method of claim 36, wherein

(a) the anti-PD-1 antibody or antigen-binding portion thereof and the anti-CTLA-4 antibody or antigen-binding portion thereof are administered within 30 minutes of each other,

(b) the anti-PD-1 antibody or antigen-binding portion thereof is administered before the anti-CTLA-4 antibody or antigen-binding portion thereof, or

(c) the anti-CTLA-4 antibody or antigen-binding portion thereof is administered before the anti-PD-1 antibody or antigen-binding portion thereof.

44. The method of claim 36, wherein the anti-PD-1 antibody or antigen-binding portion thereof is administered at a subtherapeutic dose, the anti-CTLA-4 antibody or antigen-binding portion thereof is administered at a subtherapeutic dose, or the anti-PD-1 antibody or antigen-binding portion thereof and the anti-CTLA-4 antibody or antigen-binding portion thereof are each administered at a subtherapeutic dose.

48. A kit for treating a subject afflicted with a lung cancer, the kit comprising:

(a) a dosage ranging from 0.1 mg/kg to 10 mg/kg body weight of an anti-cancer agent which is an antibody or an antigen-binding portion thereof that specifically binds to the PD-1 receptor and inhibits PD-1 activity (“

an anti-PD-1 antibody or antigen-binding portion thereof”

);

(b) a dosage of another anti-cancer agent which is

(i) a platinum-based doublet chemotherapy;

(ii) an EGFR-targeted tyrosine kinase inhibitor;

(iii) bevacizumab;

or

(iv) a dosage ranging from 0.1 mg/kg to 10 mg/kg body weight of an antibody or an antigen-binding portion thereof that specifically binds to and inhibits CTLA-4 (“

an anti-CTLA-4 antibody or antigen-binding portion thereof”

); and

(c) instructions for using the anti-PD-1 antibody or antigen binding portion thereof and the other anti-cancer agent in the method of claim 1.

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