Fgfr/pd-1 combination therapy for the treatment of cancer

Patent metadata

Field	Value
Publication number	US-2016287699-A1
Application number	US-201615079136-A
Country	US
Kind code	A1
Filing date	Mar 24, 2016
Priority date	Apr 3, 2015
Publication date	Oct 6, 2016
Grant date	—

Abstract

Provided herein are combination therapies for the treatment of cancer. In particular, the disclosed methods are directed to treatment of cancer in a patient comprising administering an antibody that blocks the interaction between PD-1 and PD-L1 and an FGFR inhibitor, wherein the antibody that blocks the interaction between PD-1 and PD-L1 and the FGFR inhibitor are administered if one or more FGFR variants are present in a biological sample from the patient.

First claim

What is claimed:

1 . A method of treating cancer in a patient, comprising:
administering to the patient a pharmaceutically effective amount of an antibody that blocks the interaction between PD-1 and PD-L1 and a pharmaceutically effective amount of an FGFR inhibitor, wherein the antibody that blocks the interaction between PD-1 and PD-L1 and the FGFR inhibitor are administered if one or more FGFR variants are present in a biological sample from the patient.

2 . The method of claim 1 , further comprising evaluating the presence of one or more FGFR variants in the biological sample before the administering step.

3 . The method of claim 1 or 2 , further comprising evaluating PD-L1 expression in the biological sample.

4 . The method of any one of the previous claims, wherein the biological sample is blood, lymph fluid, bone marrow, a solid tumor sample, or any combination thereof.

5 . The method of any one of the previous claims, wherein the administering step is performed if PD-L1 expression is low in the biological sample.

6 . The method of any one of the previous claims, wherein the cancer is lung cancer, bladder cancer, gastric cancer, breast cancer, ovarian cancer, head and neck cancer, esophageal cancer, glioblastoma, or any combination thereof.

7 . The method of claim 6 , wherein the lung cancer is non-small cell lung cancer (NSCLC) adenocarcinoma, NSCLC squamous cell carcinoma, small cell lung cancer, or any combination thereof.

8 . The method of any one of the previous claims, wherein the one or more FGFR variants comprise an FGFR mutation, an FGFR amplification, an FGFR fusion gene, or a combination thereof.

9 . The method of claim 8 , wherein the FGFR fusion gene is FGFR2:AFF3; FGFR2:BICC1; FGFR2:CASP7; FGFR2:CCDC6; FGFR2:OFD1; FGFR3:BAIAP2L1; FGFR3:TACC3-Intron; FGFR3:TACC3V1; FGFR3:TACC3V3; or a combination thereof.

10 . The method of any one of the previous claims, wherein the antibody that blocks the interaction between PD-1 and PD-L1 is an anti-PD-1 antibody, an anti-PD-L1 antibody, or a combination thereof.

11 . The method of any one of the previous claims, wherein the FGFR inhibitor is the compound of formula (I):

or a pharmaceutically acceptable salt thereof.

12 . A method of treating cancer in a patient comprising:
administering to the patient a pharmaceutically effective amount of an antibody that blocks the interaction between PD-1 and PD-L1; monitoring the efficacy of the antibody; and if the antibody is not efficacious,
evaluating a biological sample from the patient for a presence of one or more FGFR variants; and
administering to the patient a pharmaceutically effective amount of an FGFR inhibitor if the one or more FGFR variants are present in the sample.

13 . The method of claim 12 , wherein the evaluating step further comprises measuring an expression level of PD-L1 in the biological sample and wherein the second administering step comprises administering the FGFR inhibitor if the expression level of PD-L1 is low.

14 . The method of claim 12 or 13 , wherein the biological sample is blood, lymph fluid, bone marrow, a solid tumor sample, or any combination thereof.

15 . The method of any one of claims 12 - 14 , wherein the cancer is lung cancer, bladder cancer, gastric cancer, breast cancer, ovarian cancer, head and neck cancer, esophageal cancer, glioblastoma, or any combination thereof.

16 . The method of claim 15 , wherein the lung cancer is non-small cell lung cancer (NSCLC) adenocarcinoma, NSCLC squamous cell carcinoma, small cell lung cancer, or any combination thereof.

17 . The method of any one of claims 12 - 16 , wherein the one or more FGFR variants comprise an FGFR mutation, an FGFR amplification, an FGFR fusion gene, or a combination thereof.

18 . The method of claim 17 , wherein the FGFR fusion gene is FGFR2:AFF3; FGFR2:BICC1; FGFR2:CASP7; FGFR2:CCDC6; FGFR2:OFD1; FGFR3:BAIAP2L1; FGFR3:TACC3-Intron; FGFR3:TACC3V1; FGFR3:TACC3V3; or a combination thereof.

19 . The method of any one of claims 12 - 18 , wherein the antibody that blocks an interaction between PD-1 and PD-L1 is an anti-PD-1 antibody, an anti-PD-L1 antibody, or a combination thereof.

20 . The method of any one of claims 12 - 19 , wherein the FGFR inhibitor is the compound of formula (I):

or a pharmaceutically acceptable salt thereof.

Assignees

• Janssen Pharmaceutica Nv

Inventors

• Karkera Jayaprakash
• Platero Suso Jesus
• Verona Raluca
• Lorenzi Matthew V

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• C07K16/2818

  against CD28 or CD152 · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title