DRUG SELECTION FOR NON-SMALL CELL LUNG CANCER THERAPY

• US 20160032403A1
• Filed: 07/29/2015
• Published: 02/04/2016
• Est. Priority Date: 02/05/2013
• Status: Active Grant

• Current Assignee: Societe des Produits Nestle SA (Nestle SA)
• Original Assignee: Nesec SA
• Inventors: Singh, Sharat, Kim, Phillip, Lockton, Steven
• Granted Patent: US 10,640,830 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2333/71 for growth factors; for growth regulators
• CPC Class Codes: G01N 2333/82 Translation products from oncogenes
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/57423 of lung
• CPC Class Codes: G01N 33/5748 involving oncogenic proteins

Abstract

The present invention provides methods for selecting a suitable anticancer drug for the treatment of patient with non-small cell lung cancer (NSCLC). The present invention also provides methods for determining drug resistance in NSCLC patients receiving EGFR inhibitor therapy.

Claims

1. A method for selecting a suitable anticancer drug for the treatment of non-small cell lung cancer (NSCLC) in a subject, the method comprising:

(a) determining and/or quantifying the activation and/or expression level of EGFR in a cellular extract produced from an isolated cancer cell from the subject;

(b) determining and/or quantifying the activation and/or expression level of c-Met in the cellular extract produced from an isolated cancer cell from the subject;

(c) calculating a EGFR/c-MET index based upon the measurement of steps (a) and (b); and

(d) selecting a suitable anticancer drug(s) for the treatment of NSCLC based upon the a EGFR/c-MET index.

2. The method of claim 1, wherein the expression levels of EGFR and cMet are used in calculating the EGFR/c-MET index.

3. The method of claim 1, wherein the activation levels of EGFR and cMet are used in calculating the EGFR/c-MET index.

4. The method of claim 1, wherein the expression levels and/or activation levels of EGFR and cMet are determined by CEER™

.

5. The method of claim 1, wherein the expression levels of EGFR and cMet are determined by mRNA.

6. The method of claim 5, wherein the mRNA levels are measured using Northern blotting, Reverse Transcriptase Polymerase Chain Reaction (RT-PCR), or quantitative RT-PCR (qRT-PCR).

7. The method of claim 1, wherein the EGFR/c-MET index is between 0-20.

8. The method of claim 7, wherein when the EGFR/c-MET index is between 2 and 20, the subject is administered an EGFR inhibitor.

9. The method of claim 8, wherein the EGFR inhibitor is selected from the group consisting of Cetaximab, Panitumumab, Matuzumab, Nimotuzumab, ErbB1 vaccine, Erlotinib, Gefitinib, EKB 569, CL-387-785 and a combination thereof.

10. The method of claim 8, wherein the level of pHER3 indicates EGFR inhibitor resistance.

11. The method of claim 7, wherein when the EGFR/c-MET index is between 0 and 2, the subject is administered a cMET inhibitor or a combination of a cMET inhibitor and an EGFR inhibitor.

12. The method of claim 11, wherein the c-MET inhibitor is selected from the group consisting of MAG102 and MetMab, ARQ197, XL184, PF-02341066, GSK1363089/XL880, MP470, MGCD265, SGX523, PF04217903, JNJ38877605, INCB28060, AMG-458, E7050, MK-2461, BMS-777607 and a combination thereof.

13. The method of claim 1, wherein a low EGFR/c-MET index indicates progressive disease in the subject.

14. The method of claim 1, wherein a high EGFR/c-MET index indicates prolonged progression-free survival compared to a low EGFR/c-MET index.

15. The method of claim 1, wherein a EGFR mutation indicates prolonged progression-free survival compared to wild type EGFR.

16. The method of claim 15, wherein the EGFR mutation is selected from the group consisting of E709D, E709Q, E709K, E709A, E709A, G719S, G719C, G719A, G719R, S768I, T790M, L858R, L858M, L861Q and L861R.

17. The method of claim 1 wherein determining and/or quantifying the expression of HGF is used in lieu of determining and/or quantifying the expression of cMET.

18. The method of claim 1, wherein determining and/or quantifying the expression of cMET together with HGF is used in lieu of determining and/or quantifying the expression of cMET alone.

19. A method for monitoring a NSCLC subject receiving an anticancer drug, the method comprising:

(a) detecting and/or quantifying the expression level and/or activation level of EGFR in a cellular extract produced from an isolated cancer cell from the subject;

(b) detecting and/or quantifying the expression level and/or activation level of cMet in a cellular extract produced from an isolated cancer cell from the subject;

(c) determining an EGFR/cMET index based on the activation and/or expression levels of EGFR and c-Met analytes in the cellular extracts at time point 1 (t₁);

(d) repeating steps (a) and (b) to determine a EGFR/cMET index later in time based on the activation and/or expression levels of EGFR and c-Met analytes in the cellular extracts at time point 2 (t₂); and

(e) comparing the EGFR/cMET index of the earlier time point (t₁) to the EGFR/cMET index at the later time point (t₂), to monitor the subject receiving the anticancer drug.

20. The method of claim 19, wherein an EGFR/cMET index at t₂ that is greater than at t₁ indicates prolonged progression-free survival (PFS) for the subject.

21-37. -37. (canceled)