Triple Combination Therapy for Advanced Cancer Treatment
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Solution Overview
Problem
Current cancer therapies, including PD-1 antagonists and multi-RTK inhibitors like lenvatinib, and CBP/β-catenin inhibitors, often have limited efficacy when used individually, necessitating combination therapies to enhance treatment outcomes for cancers such as renal cell carcinoma, colorectal cancer, and melanoma.
Innovation Solution
A combination therapy comprising a PD-1 antagonist (e.g., pembrolizumab), lenvatinib, and a CBP/β-catenin inhibitor (E7386) is administered to patients, where the PD-1 antagonist is not atezolizumab, with lenvatinib and E7386 being used in various dosages and treatment regimens to target solid tumors effectively.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a PD-1 antagonist is used alone, then immune response is enhanced, but anti-tumor efficacy is limited
Solution Approach 1:
The patent combines a PD-1 antagonist with a multi-RTK inhibitor (lenvatinib) and a CBP/β-catenin inhibitor (E7386) into a triple combination therapy. This merging of multiple therapeutic agents with different mechanisms of action synergistically enhances anti-tumor efficacy while overcoming the limitations of monotherapy or dual therapy approaches.
2Productivity
If a multi-RTK inhibitor like lenvatinib is used alone, then tumor proliferation is inhibited, but immune response enhancement is insufficient
Solution Approach 1:
The patent integrates lenvatinib (multi-RTK inhibitor) with a PD-1 antagonist and E7386 (CBP/β-catenin inhibitor). This combination merges anti-proliferation effects with immune response enhancement, where lenvatinib inhibits tumor growth while the PD-1 antagonist and E7386 work synergistically to enhance immune-mediated tumor destruction.
3Productivity
If a CBP/β-catenin inhibitor E7386 is used alone, then tumor growth is suppressed, but overall anti-tumor effect is limited
Solution Approach 1:
The patent combines E7386 (CBP/β-catenin inhibitor) with a PD-1 antagonist and lenvatinib (multi-RTK inhibitor). This triple combination merges tumor growth suppression with immune response enhancement and anti-angiogenic effects, creating a synergistic therapeutic effect that overcomes the limitations of E7386 monotherapy.
4Reliability
If combination therapy is used, then anti-tumor effect is enhanced, but treatment complexity increases
Solution Approach 1:
The patent merges three therapeutic agents (PD-1 antagonist, lenvatinib, and E7386) into a coordinated triple combination therapy. While this increases treatment complexity, the synergistic effects of combining agents with complementary mechanisms of action produce significantly enhanced anti-tumor efficacy that outweighs the increased complexity, particularly for advanced and metastatic cancers.
Data Source
AI summary
The present disclosure describes a combination therapy comprising an antagonist of Programmed Death 1 receptor (PD-1), a lenvatinib or a pharmaceutically acceptable salt thereof, and (6S,9aS)-N-benzyl-8-({6-[3-(4-ethylpiperazin-1-yl)azetidin-1-yl]pyridin-2-yl}methyl)-6-(2-fluoro-4-hydroxybenzyl)-4,7-dioxo-2-(prop-2-en-1-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide (E7386) or a pharmaceutically acceptable salt thereof,—and the use of the combination therapies for the treatment of a cancer.