Combination therapy involving diaryl macrocyclic compounds

Inventors

Cui, Jingrong Jean • Zhai, Dayong

Assignees

Turning Point Therapeutics Inc

Abstract

The present disclosure relates to methods and compositions for treating cancer with a diaryl macrocycle in combination with at least one other cancer therapeutic, such as an EGFR inhibitor.

Core Innovation

The invention relates to cancer therapeutics using diaryl macrocyclic compounds that inhibit FAK, SRC, and JAK2. The document discloses compounds having a structure defined as Formula I or Formula II, with substituent scope defined by variables such as X, R1-R6, and n, and describes methods of treating cancer in a patient in need thereof by administering a therapeutically effective amount of a compound having a structure as provided in the description, or a pharmaceutically acceptable salt thereof.

The core combination aspect is administering the FAK/SRC/JAK2 inhibitory diaryl macrocyclic compound together with an EGFR inhibitor. The document specifies that an EGFR inhibitor is administered as part of the method, with example EGFR inhibitors including cetuximab, necitumumab, panitumumab, afatinib, osimertinib, dacomitinib, and gefitinib.

The cancer is specified as lung cancer in the relevant independent claim, including non-small cell lung cancer (NSCLC), adenocarcinoma, lung squamous cell carcinoma, large cell carcinoma, large cell neuroendocrine tumor, and small cell lung cancer (SCLC). The document also describes fixed or free combination medicaments, simultaneous administration, sequential administration, and references synergistic compositions and anti-tumor activity via tyrosine kinase inhibition.

Claims Coverage

The independent claim covers a cancer treatment method for lung cancer using a therapeutically effective amount of a specific diaryl macrocyclic compound (or pharmaceutically acceptable salt) together with a therapeutically effective amount of an EGFR inhibitor selected from afatinib, dacomitinib, gefitinib, and osimertinib (or pharmaceutically acceptable salt). The claim set includes six inventive features.

The inventive coverage centers on treating lung cancer using a diaryl macrocyclic compound having a defined structure (or its pharmaceutically acceptable salt) that is administered with an EGFR inhibitor selected from afatinib, dacomitinib, gefitinib, and osimertinib (or its pharmaceutically acceptable salt). Dependent claims further narrow lung cancer histologic types, define daily dosing ranges for both components, and restrict administration timing to simultaneous or sequential regimens with EGFR inhibitor first.

Stated Advantages

Documented Applications