The present invention is directed to imidazo[1,2-b][1,2,4]triazines and imidazo[1,2-a]pyrimidines, and pharmaceutical compositions thereof, which are inhibitors of kinases such as c-Met and are useful in the treatment of cancer and other diseases related to the dysregulation of kinase pathways.

The present disclosure provides treatment modalities, e.g., strategies, treatment methods, patient stratification methods, combinations, and compositions that are useful for the treatment of disorders, e.g., proliferative disorders, such as certain cancer. Some aspects of this disclosure provide treatment modalities, methods, strategies, compositions, combinations, and dosage forms for the treatment of cell proliferative disorders, e.g., cancers with decreased activity or function, or loss of function, of SMARCA4 with a SMARCA2 antagonist.

The present disclosure provides treatment modalities, e.g., strategies, treatment methods, patient stratification methods, combinations, and compositions that are useful for the treatment of disorders, e.g., proliferative disorders, such as certain cancer. Some aspects of this disclosure provide treatment modalities, methods, strategies, compositions, combinations, and dosage forms for the treatment of cell proliferative disorders, e.g., cancers with decreased activity or function, or loss of function, of SMARCA4 with a SMARCA2 antagonist.

The present disclosure provides a method of treating cancer in a subject in need thereof comprising administering a checkpoint inhibitor to the subject, and administering a MALT-1 inhibitor according to an intermittent dosage regimen.

The present disclosure provides a method of treating cancer in a subject in need thereof comprising administering a checkpoint inhibitor to the subject, and administering a MALT-1 inhibitor according to an intermittent dosage regimen.

The present invention includes methods of monitoring measurable residual disease in patients suffering from a proliferative disorder, determining which patients could benefit from treatment or intervention with crenolanib or salt in reducing residual disease and maintaining remission, and administering a therapeutically effective amount of crenolanib as a single agent or sequentially or concomitantly with another therapeutic agent.

The present invention includes methods of monitoring measurable residual disease in patients suffering from a proliferative disorder, determining which patients could benefit from treatment or intervention with crenolanib or salt in reducing residual disease and maintaining remission, and administering a therapeutically effective amount of crenolanib as a single agent or sequentially or concomitantly with another therapeutic agent.

The present invention includes methods of monitoring measurable residual disease in patients suffering from a proliferative disorder, determining which patients could benefit from treatment or intervention with crenolanib or salt in reducing residual disease and maintaining remission, and administering a therapeutically effective amount of crenolanib as a single agent or sequentially or concomitantly with another therapeutic agent.

A composition of substituted crotonamide pharmaceutical and a preparation method therefor. The pharmaceutical composition comprises 5-50 parts of (E)-N-(3-cyano-7-ethoxy-4-(3-ethynylphenylamino)quinolin-6-yl)-4-(dimethylamino)but-2-enamide maleate, 40-120 parts of a filler, 2-20 parts of a disintegrant, 0-6 parts of an adhesive, and 0.5-5 parts of a lubricant. The filler is selected from carbohydrates.

A composition of substituted crotonamide pharmaceutical and a preparation method therefor. The pharmaceutical composition comprises 5-50 parts of (E)-N-(3-cyano-7-ethoxy-4-(3-ethynylphenylamino)quinolin-6-yl)-4-(dimethylamino)but-2-enamide maleate, 40-120 parts of a filler, 2-20 parts of a disintegrant, 0-6 parts of an adhesive, and 0.5-5 parts of a lubricant. The filler is selected from carbohydrates.