Novartis Ag

Array Biopharma Inc.

Novartis Vaccines & Diagnostics, Gmbh

Darrin Stuart

Giordano Caponigro

Paul A Renhowe

Daniel J Poon

Savithri Ramurthy

Cynthia Shafer

Christopher McBride

Sharadha Subramanian

Barry Haskell Levine

Payman Amiri

Teresa E Pick

Mina E Aikawa

Jeffrey H Dove

Matthew John Meyer

Vesselina Cooke

Laure De Parseval

Carlos Garcia-Echeverria

Christine Fritsch

Sunkyu Kim

Sauveur-Michel Maira

Scott Delach

Susan Wee

Tobi Nagel

Alice Loo

Meghna Das Thakur

Laure Moutouh-De Parseval

Christopher Mcbride

The present invention relates to a combination treatment which comprises (a) at least one ERK inhibitor preferably Compound B as described herein, and (b) a c-RAF inhibitor or a pharmaceutically acceptable salt thereof, preferably Compound A, which may be combined into a single pharmaceutical composition or prepared for separate or sequential administration. It includes a c-RAF inhibitor and an ERK inhibitor prepared for simultaneous, separate or sequential administration for the treatment of a proliferative disease, particularly an advanced solid tumor that harbors a Mitogen-activated protein kinase (MAPK) alteration, and includes methods of using these compounds in combination as well as a commercial package comprising such combination.

Therapeutic combinations comprising a c-RAF inhibitor

The present invention relates to a method of treating a patient with a serine/threonine kinase inhibitor wherein resistance to the treatment with a serine/threonine kinase inhibitor is suppressed by administering the serine/threonine kinase inhibitor on an intermittent dosing schedule.

Method of treating a proliferative disease

Therapeutic uses of a C-RAF inhibitor

Reversing resistance to a B-Raf inhibitor for the treatment of a proliferative disease by obtaining a tumor sample from the patient and testing it for genetic alterations in a panel of genes comprising BRAF, CRAF, CCND1, CDK4, HER2, IGF-1R, cMET, FGFR1, FGFR2, FGFR3 EGFR, MAP2K1, MAP2K2, NRAS, KRAS HRAS, PTEN, PIK3CA, and P16 and administering a drug combination therapy comprising the B-Raf inhibitor and a second inhibitor which overcomes resistance to the B-Raf inhibitor, which second inhibitor is selected based on genetic alterations discovered in the tumor sample.

Combination therapy

A pharmaceutical combination comprising (a) CDK4/6 inhibitor (b) a B-Raf inhibitor, and optionally (c) a MEK 1/2 inhibitor; combined preparations and pharmaceutical compositions thereof; the uses of such combination in the treatment of proliferative diseases; and methods of treating a subject suffering from a proliferative disease comprising administering a therapeutically effective amount of such combination.

Pharmaceutical combinations of a CDK4/6 inhibitor and a B-RAF inhibitor

A pharmaceutical combination comprising (a) a B-Raf inhibitor, (b) a EGFR inhibitor and, optionally, (c) a PI3K inhibitor; the uses of such combination in the treatment of proliferative diseases; and methods of treating a subject suffering from a proliferative disease comprising administering a therapeutically effective amount of such combination.

Pharmaceutical combinations comprising a B-RAF inhibitor, and EGFR inhibitor and optionally a PI3K-&#x3b1; inhibitor

The invention relates to a pharmaceutical combination which comprises (a) a phosphoinositide 3-kinase inhibitor compound and (b) a compound which modulates the Ras/Raf/Mek pathway for the treatment of a proliferative disease, especially a solid tumor disease; a pharmaceutical composition comprising such a combination; the use of such a combination for the preparation of a medicament for the treatment of a proliferative disease; a commercial package or product comprising such a combination as a combined preparation for simultaneous, separate or sequential use; and to a method of treatment of a warm-blooded animal, especially a human.

Combination of (a) a phosphoinositide 3-kinase inhibitor and (b) a modulator of RAS/RAF/MEK pathway

New substituted benzimidazole compounds, compositions, and methods of inhibition of kinase activity associated with tumorigenesis in a human or animal subject are provided. In certain embodiments, the compounds and compositions are effective to inhibit the activity of at least one serine/threonine kinase or receptor tyrosine kinase. The new compounds and compositions may be used either alone or in combination with at least one additional agent for the treatment of a serine/threonine kinase- or receptor tyrosine kinase-mediated disorder, such as cancer.

Substituted benzimidazoles and methods of their use

Growing community of inventors

Pleasant Hill, CA, United States of America

Darrin Stuart