Therapeutic agent for solid cancers, which comprises Axl inhibitor as active ingredient
Inventors
Takayama, Koichi • Yamada, Tadaaki • Yasuhiro, Tomoko • Tanaka, Kohei
Assignees
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Publication Number
US-11826363-B2
Publication Date
2023-11-28
Expiration Date
Abstract
A therapeutic agent for treatment of solid cancers, including, as an effective component, N-{5-[(6,7-dimethoxy-4-quinolinyl)oxy]-2-pyridinyl}-2,5-dioxo-1-phenyl-1,2,5,6,7,8-hexahydro-3-quinolinecarboxamide, a pharmaceutically acceptable salt thereof, or a hydrate of the compound or the salt in combination with osimertinib or a pharmaceutically acceptable salt thereof. The combination of the present invention has strong antitumor effect and is therefore useful for treatment of solid cancers.
Core Innovation
The invention discloses a therapeutic combination for solid cancers comprising an Axl inhibitor, N-{5-[(6,7-dimethoxy-4-quinolinyl)oxy]-2-pyridinyl}-2,5-dioxo-1-phenyl-1,2,5,6,7,8-hexahydro-3-quinolinecarboxamide (compound A, including salts and hydrates) administered with osimertinib. The invention is directed to treating EGFR inhibitor-resistant non-small cell lung cancer (NSCLC) in a subject in need thereof.
The problem addressed is EGFR inhibitor-resistant NSCLC, specifically including EGFR T790M mutation-positive NSCLC as an EGFR inhibitor-resistant form. The disclosed combination is positioned as a way to provide strong antitumor activity and improved clinical outcomes in the setting of resistance to EGFR inhibitors.
The combination is described as suppressing metastasis and recurrence, and as reducing toxicity via dose reduction. The document also includes in vitro evidence using an EGFR exon 19 deletion NSCLC cell line, reporting a synergistic antitumor effect, with a median combination index (CI) of less than 0.30 for compound A plus osimertinib.
Claims Coverage
The independent claim covers a treatment method for EGFR inhibitor-resistant NSCLC, comprising a specified Axl inhibitor (compound A or its pharmaceutically acceptable salt or hydrate) in combination with osimertinib (or its pharmaceutically acceptable salt), with the resistance limited to EGFR T790M mutation-positive NSCLC. Dependent claims refine the osimertinib-related context and narrow the resistance subtype to gefitinib-resistant lung cancer.
Axl inhibitor in combination with osimertinib for EGFR inhibitor-resistant NSCLC
Administering an effective amount of N-{5-[(6,7-dimethoxy-4-quinolinyl)oxy]-2-pyridinyl}-2,5-dioxo-1-phenyl-1,2,5,6,7,8-hexahydro-3-quinolinecarboxamide (compound), a pharmaceutically acceptable salt thereof, or a hydrate of the compound or the salt, in combination with osimertinib or a pharmaceutically acceptable salt thereof, to treat an EGFR inhibitor-resistant NSCLC subject in need thereof.
EGFR inhibitor-resistant NSCLC limited to EGFR T790M mutation-positive NSCLC
Wherein the EGFR inhibitor-resistant NSCLC is EGFR T790M mutation-positive NSCLC.
Osimertinib treatment refinement
The method further includes treating the subject with osimertinib or a pharmaceutically acceptable salt thereof.
Gefitinib-resistant lung cancer refinement
The EGFR inhibitor-resistant lung cancer is gefitinib-resistant lung cancer.
Overall, the claim set centers on combining compound A (or salts/hydrates) with osimertinib for EGFR inhibitor-resistant NSCLC, with the resistance subtype specified as EGFR T790M mutation-positive NSCLC, and further refined by dependent claims to include gefitinib-resistant lung cancer and an osimertinib treatment context.
Stated Advantages
Strong antitumor activity.
Improved clinical outcomes including PFS, OS, DFS, TTP, EFS, and RFS.
Metastasis suppression.
Recurrence suppression.
Reduced toxicity via dose reduction.
Documented Applications
Treating EGFR inhibitor-resistant non-small cell lung cancer (NSCLC) in a subject in need thereof, including EGFR T790M mutation-positive NSCLC, using compound A (including salts/hydrates) with osimertinib.
Addressing EGFR inhibitor resistance settings described as gefitinib-resistant lung cancer and EGFR T790M mutation-positive NSCLC.
Solid cancers (broad set of solid tumor types is described) using the compound A plus osimertinib combination.
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