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Methods for treating cancer using PI3K inhibitor and MEK inhibitor

A cancer, dose technique, applied in for reference. , including at least one periodic field

Inactive Publication Date: 2015-02-04
SANOFI SA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] However, there remains a need for cancer therapies that more effectively inhibit cell proliferation and tumor growth while minimizing patient toxicity

Method used

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  • Methods for treating cancer using PI3K inhibitor and MEK inhibitor
  • Methods for treating cancer using PI3K inhibitor and MEK inhibitor
  • Methods for treating cancer using PI3K inhibitor and MEK inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0076] Example 1: Preclinical experiments

[0077] Six patient-derived colorectal cancer (CRC) xenograft models were used to study the antitumor activity and terminal Pharmacodynamic (PD) effects. The selected models contained KRAS mutations alone, KRAS and BRAF double mutations, or KRAS and PIK3CA double mutations (Table 1).

[0078] Table 1. Selected patient-derived CRC xenograft models for activity studies with compound (2) or compound (3) in combination with compound (1)

[0079]

[0080]The standard experimental design for these studies involved oral administration of Compound (2) (20 mg / kg qd), Compound (3) (75 mg / kg qd), and Compound (1) (20 mg / kg qd), except for 1 model, CR- IGR-0032-P (where a dose of 10 mg / kg qd was used)). A single dose of compound (2) or compound (3) was combined with a certain dose of compound (1) in the combination group. Once established solid tumors are staged (staging size is approximately 150-170 mm for most subcutaneous xenograft mode...

Embodiment 2

[0111] Example 2: Phase Ib Trial in Patients with Solid Tumors

[0112] A non-comparative open-label, non-randomized combination dose-escalation phase Ib trial was conducted using a classic "3+3" design in the dose-escalation cohort. In parallel with the dose escalation cohort, additional subjects may enter the lower dose level (LDL) cohort for further evaluation of safety, PK, antitumor and Pd as determined by the Safety Monitoring Committee (SMC) active. After reaching the maximum tolerated dose (MTD), the MTD population(s) will be expanded with additional subjects to confirm the MTD(s). Following confirmation of the MTD(s), additional subjects with specific tumor diagnoses will be entered into up to four disease-specific expansion cohorts as determined by the SMC.

[0113] A maximum of 90 subjects are expected to enter and receive treatment in the dose escalation and LDL / MTD cohorts of the trial. Approximately 80 additional subjects are planned to enter the four disease-...

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Abstract

Methods of treating patients with cancer are provided, wherein the methods comprise administering to the patient an effective amount of a MEK inhibitor and an effective amount of a PI3K inhibitor. Compositions in which the MEK and PI3K inhibitors are combined also are described.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of priority of U.S. Provisional Application 61 / 621,252 filed April 6, 2012, U.S. Provisional Application 61 / 771,457, filed March 1, 2013, and French Patent Application 1351158, filed February 12, 2013 , the above application is incorporated into this application by reference. Background technique [0003] There is a continuing need in the art for more effective methods and compositions for the treatment of cancer. The present application relates generally to compositions and methods for treating cancer and more particularly to compositions and methods comprising mitogen activated protein kinase (MEK) pathway inhibitors and / or phosphoinositide 3-kinase (phosphoinositide 3-kinase) Kinase (PI3K) pathway inhibitor compositions and methods. [0004] Tumor cells treated with MEK kinase inhibitors typically respond by inhibiting ERK phosphorylation, downregulating cyclin D, inducing G1 arre...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61P35/00A61K31/44A61K31/519
CPCA61K31/519A61K31/44A61K45/06A61P1/00A61P11/00A61P15/08A61P35/00A61P43/00A61K2300/00
Inventor K·许J·拉格尔J·A·M·奥格登
Owner SANOFI SA