FGFR4 and CDK4/6 Inhibitor Combination for HCC

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Solution Overview

Problem

Current treatments for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC) lack effective solutions, particularly in addressing the overactivation of signaling pathways such as FGF19/FGFR4 and CDK4/6, which contribute to tumor growth and progression.

Innovation Solution

A combination therapy involving a selective FGFR4 inhibitor, Compound 1, and a CDK4/6 inhibitor, such as ribociclib or palbociclib, administered orally to inhibit tumor growth by targeting these pathways simultaneously.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If combination therapy with Compound 1 and CDK4/6 inhibitor is used, then antitumor effect is enhanced, but treatment complexity increases

Engineering Contradiction:
Improveantitumor effectVSAvoidtreatment complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines Compound 1 (FGFR4 inhibitor) with CDK4/6 inhibitors in a single treatment regimen, merging two therapeutic agents that target different signaling pathways (FGF19/FGFR4 and CDK4/6) to achieve synergistic antitumor effects while managing the complexity through coordinated administration protocols

Inventive Principle:
Principle #5Merging (Combining)

2Volume of moving object

If combination therapy with Compound 1 and CDK4/6 inhibitor is used, then tumor volume reduction is increased, but dosage optimization difficulty increases

Engineering Contradiction:
Improvetumor volumeVSAvoiddosage optimization
Core Design Contradiction:
Volume of moving objectVSManufacturing precision

Solution Approach 1:

The patent systematically varies the dosage parameters of Compound 1 and CDK4/6 inhibitors to identify optimal treatment regimens, adjusting concentrations and administration schedules to maximize tumor volume reduction while establishing standardized dosage protocols to manage optimization complexity

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP3503923B1Combination therapies for the treatment of hepatocellular carcinoma
Publication Date: 2023.10.04 EISAI R&D MANAGEMENT CO LTD
  • EP3503923B1 patent drawingFigure 1A~1B
  • EP3503923B1 patent drawingFigure 1C
  • EP3503923B1 patent drawingFigure 2A~2B

AI summary

Provided herein is a combination therapy useful for the treatment hepatocellular carcinoma and/or intrahepatic cholangiocarcinoma. The combination comprises an FGFR4 inhibitor and a CDK 4/6 inhibitor.