Celgene Corporation

Agios Pharmaceuticals, Inc.

Les Laboratoires Servier

Jorge DiMartino

Kyle MacBeth

Aaron Nguyen

Samuel V Agresta

Vivek Saroj Kumar Chopra

Laurie A Kenvin

Qiang Xu

Robert Douglas Knight

Krishnan Viswanadhan

Kyle J Macbeth

Laurie Kenvin

Provided are methods and compositions for treating cancers in patients carrying an IDH2 mutation using a combination of an inhibitor of a mutant IDH2 enzyme and a DNA demethylating agent.

Combination therapy for treating malignancies

Provided are methods and compositions for treating hematological malignancies in patients carrying an IDH1 mutation using a combination of an inhibitor of mutant IDH1 enzyme, (S)-N-((S)-1-(2-chlorophenyl)-2-((3,3-difluorocyclobutyl)amino)-2-oxoethyl)-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide, or a pharmaceutically acceptable salt thereof (COMPOUND 2) and a DNA demethylating agent.

Provided herein are methods for treating subjects having a cancer, such as a relapsed or refractory solid tumor, wherein the method comprises administering to the subject a cytidine analog. In certain of the methods, the cytidine analog is administered alone or in combination with one or more anti-cancer agents. Also provided are methods for using a cytidine analog, to treat diseases and disorders including disorders related to abnormal cell proliferation, hematologic disorders, and immune disorders, among others. In certain of the methods, the cytidine analog is formulated in an oral dosage form and administered orally.

Methods for treating cancers using oral formulations of cytidine analogs

Provided herein are methods of treating cancer in a cancer patient by overcoming resistance of a cancer cell to a drug, or methods of overcoming resistance of a cancer cell to a drug, comprising administering to the patient an effective amount of (i) an EGFR tyrosine kinase inhibitor or a B-Raf kinase inhibitor, and (ii) an HDAC inhibitor. Also provided are methods for inhibiting or preventing proliferation of drug tolerant persister (DTP) cells comprising contacting these cells with an EGFR tyrosine kinase inhibitor or B-Raf kinase inhibitor in combination with an HDAC inhibitor. Yet also provided are methods for inhibiting or preventing formation of colonies of drug tolerant expanded persister (DTEP) cells comprising contacting these cells with an EGFR tyrosine kinase inhibitor or B-Raf kinase inhibitor in combination with an HDAC inhibitor.

Inhibition of drug resistant cancer cells

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Belmont, CA, United States of America

Jorge DiMartino