Anti-ctla4 antibody and indolinone combination therapy for...

A - Human Necessities – 61 – K

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A61K 39/395 (2006.01) A61P 35/00 (2006.01) C07K 16/28 (2006.01)

Patent

CA 2602316

The invention relates to administration of an anti-CTLA4 antibody, particularly human antibodies to human CTLA4, such as those having amino acid sequences of antibodies 3.1.1 , 4.1.1 , 4.8.1 , 4.10.2, 4.13.1 , 4.14.3, 6.1.1 , ticilimumab (also referred to as 11.2.1 or CP- 675,206), 11.6.1 , 11.7.1 , 12.3.1.1 , 12.9.1.1 , and ipilimumab (also referred to as 10D1 or MDX-010), in combination with an indolinone receptor tyrosine kinase inhibitor (RTKI), e.g., N-[2-diethylamino]ethyl]-5-[(Z)-(5-fluoro-2-oxo-1 ,2-dihydro-3H-indol-3- ylidene)methyl]-2,4- dimethyl-1 H-pyrrole-3-carboxamide (compound 1 ), N-[2- (ethylamino)ethyl]-5-[(Z)-(5-fluoro-2- oxo-1 ,2-dihydro-3H-indol-3- ylidene)methyl]-2,4-dimethyl-1 H-pyrrole-3-carboxamide (compound 2), and 5- [(Z)-(5-fluoro-2-oxo-1 ,2-dihydro-3H-indol-3-ylidene)methyl]-N-[(2S)-2- hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1 H-pyrrole-3-carboxamide (compound 3), for treatment of cancer. The invention relates to administering a combination of an anti-CTLA4 antibody and an indolinone RTKI such as, inter alia, compound 1. The invention relates to neoadjuvant, adjuvant, first-line, second-line, and third-line therapy of cancer, whether localized or metastasized, and at any point(s) along the disease continuum (e.g., at any stage of the cancer).

L'invention concerne l'administration d'un anticorps anti-CTLA4, en particulier des anticorps humains du CTLA4 humain, tels que ceux comprenant des séquences d'acides aminés d'anticorps 3.1.1, 4.1.1, 4.8.1, 4.10.2, 4.13.1, 4.14.3, 6.1.1, ticilimumab (également appelé 11.2.1 ou CP-675,206), 11.6.1, 11.7.1, 12.3.1.1, 12.9.1.1 et ipilimumab (également appelé 10D1 ou MDX-010), associé à un inhibiteur des récepteurs tyrosine kinases de l'indolinone (RTKI), par exemple N-[2-diéthylamino]éthyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidène)méthyl]-2,4-diméthyl-1H-pyrrole-3-carboxamide (composé 1), N-[2-(éthylamino)éthyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidène)méthyl]-2,4-diméthyl-1H-pyrrole-3-carboxamide (composé 2), et 5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidène)méthyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-diméthyl-1H-pyrrole-3-carboxamide (composé 3), dans le traitement du cancer. L'invention concerne également l'administration d'une association d'anticorps anti-CTLA4 et de RTKI d'indolinone, tel que, entre autres, le composé 1. L'invention concerne encore un traitement néoadjuvant, adjuvant, de première ligne, de deuxième ligne et de troisième ligne du cancer, qu'il s'agisse d'un cancer localisé ou métastasé, mis en oeuvre à n'importe quel moment de l'évolution de la maladie (à n'importe quel stade du cancer, par exemple).

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