US 2020/0368238 A1 · SHP2 INHIBITOR COMPOSITIONS AND METHODS FOR TREATING CANCER

Abstract

The present invention is directed to compositions and methods of treating or preventing diseases or disorders with inhibitors of SHP2, alone, and in combination with other therapeutic agents such as RAS pathway inhibitors (e.g., MEK inhibitors); methods of establishing appropriate treatment plans for subjects based upon the expression of one or more biomarker indicative of SHP2 inhibitor sensitivity; and methods of determining sensitivity to a SHP2 inhibitor based on a phosphorylation status of SHP2.

Claims147

Dependent claims

A method of treating a subject having a disease or disorder comprising a cell containing a mutation encoding the KRASG12C variant, comprising providing to the subject an inhibitor of SHP2.

(canceled)

A method of treating a subject having a disease or disorder associated with a RAS pathway mutation in a cell of the subject that renders the cell at least partially dependent on signaling flux through SHP2, comprising providing to the subject an inhibitor of SHP2.

(canceled)

A method for treating a subject having a tumor comprising:

(a) determining whether a biological sample obtained from the subject is classified as a KRAS mutant;
and
(b) administering to the subject an inhibitor of SHP2 if the biological sample is classified as a KRASG12C mutant, a KRASG12D mutant, a KRASG12S mutant, or a KRASG12V mutant.

A method for treating a subject having a tumor comprising:

(a) determining whether a biological sample obtained from the subject is classified as an NF1LOF mutant;
and
(b) administering to the subject an inhibitor of SHP2 if the biological sample is classified as an NF1LOF mutant.

A method for treating a subject having a tumor comprising:

(a) determining whether a biological sample obtained from the subject is classified as an Class 3 BRAF mutant;
and
(b) administering to the subject an inhibitor of SHP2 if the biological sample is classified as an Class 3 BRAF mutant.

(canceled)

A method for treating or preventing drug resistance in a subject receiving administration of a RAS pathway inhibitor, comprising administering to the subject an inhibitor of SHP2.

(canceled)

The method of any one of the preceding claims, wherein the inhibitor of SHP2 is selected from (i) Compound A;

(ii) Compound B;
(iii) SHP099;
(iv)NSC-87877;
(v) a SHP2 inhibitor compound of any one of Formula I, of Formula II, of Formula III, of Formula I-V1, of Formula I-V2, of Formula I-W, of Formula I-X, of Formula I-Y, of Formula I-Z, of Formula IV, of Formula V, of Formula VI, of Formula IV-X, of Formula IV-Y, of Formula IV-Z, of Formula VII, of Formula VIII, of Formula IX, and of Formula X;
(vi) TNO155;
(vii) Compound C, (viii) a compound from Table 1, disclosed herein;
(ix) a compound from Table 2, disclosed herein;
and (x) a combination thereof.

5 more elements

A combination therapy comprising a RAS pathway inhibitor and an inhibitor of SHP2.

(canceled)

A pharmaceutical composition comprising a RAS pathway inhibitor, an inhibitor of SHP2, and one or more pharmaceutically acceptable carrier, excipient, diluent, and/or surfactant.

(canceled)

The method of any one of the preceding claims, wherein the inhibitor of SHP2 is selected from (i) Compound A;

(ii) Compound B;
(iii) SHP099;
(iv)NSC-87877;
(v) a SHP2 inhibitor compound of any one of Formula I, of Formula II, of Formula III, of Formula I-V1, of Formula I-V2, of Formula I-W, of Formula I-X, of Formula I-Y, of Formula I-Z, of Formula IV, of Formula V, of Formula VI, of Formula IV-X, of Formula IV-Y, of Formula IV-Z, of Formula VII, of Formula VIII, of Formula IX, and of Formula X;
(vi) TNO155;
(vii) Compound C, (viii) a compound from Table 1, disclosed herein;
(ix) a compound from Table 2, disclosed herein;
and (x) a combination thereof.

5 more elements

(canceled)

A method of treating a subject having a tumor, comprising contacting a tumor cell in the tumor in the subject with a combination therapy comprising a MEK inhibitor and a inhibitor of SHP2.

(canceled)

A method of treating a subject having a tumor, comprising contacting a tumor cell of the tumor in the subject with a combination therapy comprising trametinib (GSK1120212) and Compound C.

(canceled)

Dependencies are inferred from the claim text.

Shp2 inhibitor compositions and methods for treating cancer

Life of this patent

Shp2 inhibitor compositions and methods for treating cancer

Life of this patent

Abstract

Claims147