PD-1 Antagonist and Multi-RTK Inhibitor Combination Therapy
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Solution Overview
Problem
Current cancer therapies, including PD-1 antagonists and multi-RTK inhibitors, often fail to achieve effective anti-tumor responses in all patients when used individually, necessitating a combination therapy to enhance treatment efficacy.
Innovation Solution
A combination therapy comprising a PD-1 antagonist, such as pembrolizumab, and a multi-RTK inhibitor, specifically lenvatinib or its pharmaceutically acceptable salts, is administered to patients with cancers that test positive for PD-L1 expression, where the PD-1 antagonist and multi-RTK inhibitor are formulated to inhibit key kinase activities and tumor growth pathways.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a PD-1 antagonist is used alone for cancer treatment, then immune action against tumor cells is enhanced, but anti-tumor response is insufficient in many patients
Solution Approach 1:
The patent combines a PD-1 antagonist with a multi-RTK inhibitor (lenvatinib) to create a combination therapy that targets both immune signaling and tumor proliferation pathways simultaneously. This merging of two therapeutic mechanisms addresses the insufficiency of single-agent therapy by attacking the tumor through multiple concurrent pathways, thereby improving overall anti-tumor response and treatment efficacy.
2Reliability
If a multi-RTK inhibitor is used alone for cancer treatment, then tumor proliferation is inhibited, but anti-tumor response is insufficient in many patients
Solution Approach 1:
The patent merges a multi-RTK inhibitor with a PD-1 antagonist to create a combination therapy that simultaneously inhibits tumor proliferation pathways and enhances immune recognition. This combination addresses the insufficiency of multi-RTK inhibitors alone by adding an immune activation component, thereby improving overall anti-tumor response and treatment efficacy.
3Productivity
If combination therapy is used to enhance treatment efficacy, then anti-tumor effect is improved, but treatment complexity increases
Solution Approach 1:
The combination therapy is administered as two separate agents with distinct mechanisms of action, allowing for segmented targeting of different pathways (immune signaling and proliferation). This segmentation enables the complexity to be managed through modular therapy design, where each agent can be optimized independently while contributing to the overall anti-tumor effect.
Data Source
AI summary
The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a multi-RTK inhibitor, and the use of the combination therapies for the treatment of cancer. The multi-RTK inhibitor may be represented by Formula (I):wherein R1 is C1-6 alkyl or C3-8 cycloalkyl, R2 is a hydrogen atom or C1-6 alkoxy, and R3 is a hydrogen atom or a halogen atom. A tumor therapeutic agent is disclosed that combines a compound or pharmaceutically acceptable salt thereof represented by Formula I and an anti-PD-1 antibody.