Compound 1 and Checkpoint Inhibitor Combination for Cancer Treatment
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Solution Overview
Problem
Current cancer treatments, particularly those involving immune checkpoint inhibitors, face limitations in efficacy as they only achieve durable clinical responses in a small percentage of patients and many tumors are resistant or become refractory, highlighting the need for new therapies targeting AXL and Mer tyrosine kinases.
Innovation Solution
Administration of Compound 1, either as a single agent or in combination with checkpoint inhibitors like PD-1, PD-L1, or CTLA-4 inhibitors, to treat cancer, including urothelial carcinoma, with dosages ranging from 5 mg to 100 mg, aiming to enhance anti-tumor immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint inhibitors are used to treat cancer, then clinical responses are improved in some patients, but durable responses only occur in 10-45% of patients and many tumors become resistant
Solution Approach 1:
The patent combines immune checkpoint inhibitors with AXL tyrosine kinase inhibitors in a dual-target therapy approach. This merging of two different therapeutic mechanisms addresses the limitation of single-agent checkpoint inhibitors by simultaneously blocking immune suppression while inhibiting tumor growth pathways, thereby improving durable response rates and overcoming tumor resistance.
Solution Approach 2:
The invention creates a composite therapeutic regimen combining two distinct drug classes (checkpoint inhibitors and AXL inhibitors). This composite approach leverages the complementary mechanisms of action to achieve synergistic anti-tumor effects, where the AXL inhibitor component addresses resistance mechanisms that limit checkpoint inhibitor efficacy alone.
2Adaptability or versatility
If AXL inhibitors are developed to target multiple kinase receptors, then cancer therapy options are expanded, but selectivity for AXL is reduced
Solution Approach 1:
The patent employs AXL inhibitors with optimized binding characteristics that demonstrate preferential affinity for AXL over other kinase receptors. This local quality approach ensures that the inhibitor selectively targets the AXL receptor at the molecular level while maintaining the ability to treat multiple cancer types that express AXL, thus achieving both selectivity and versatility.
Data Source
AI summary
The present invention relates to combinations comprising a checkpoint inhibitor and a c-Met inhibitor, Compound 1. The invention also relates to crystalline forms of the free base of Compound 1, as well as crystalline forms of salts of Compound 1, in combination with a checkpoint inhibitor. The invention also relates to pharmaceutical compositions comprising these combinations. The invention further relates to methods of treating cancer by administering Compound 1 as a single agent or a combination described herein.