KRASG12C Inhibitor–VEGF Antagonist Combination for Solid Tumors

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Solution Overview

Problem

There is a need for effective therapies and combination therapies for treating cancers such as lung cancer, colorectal cancer, hepatocellular carcinoma, breast cancer, renal cell carcinoma, endometrial cancer, ovarian cancer, and pancreatic cancer harboring KRasG12C mutations, as existing treatments provide limited benefit and are incurable.

Innovation Solution

A combination therapy comprising a KRasG12C inhibitor (Compound 1) and an anti-VEGF antibody, such as bevacizumab, administered in specific dosing schedules to target KRasG12C-positive tumors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing chemotherapies and targeted therapies are used for KRasG12C-positive tumors, then treatment options are available, but the benefit is limited and tumors remain incurable

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidtumor response to therapy

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines a KRasG12C inhibitor with a VEGF inhibitor in a dual-agent therapy regimen. This combination targets two different pathways simultaneously: the KRAS signaling pathway (cell proliferation) and the VEGF pathway (angiogenesis), thereby overcoming the limited efficacy of single-agent therapies and improving overall treatment effectiveness for KRasG12C-positive tumors

Inventive Principle:

Principle #5Merging (Combining)

2Reliability

If KRasG12C inhibitor and VEGF inhibitor are administered in combination, then treatment effectiveness is improved, but dosing schedule complexity increases

Engineering Contradiction:

Improvetreatment effectivenessVSAvoiddosing schedule complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent implements a periodic dosing schedule where the KRasG12C inhibitor is administered daily for 21 days followed by a 7-day break, and the VEGF inhibitor is administered every 3 weeks. This periodic regimen with defined cycles simplifies the management of combination therapy by establishing predictable intervals for each agent, reducing the perceived complexity while maintaining treatment effectiveness

Inventive Principle:

Principle #19Periodic action

Data Source

PatentUS12409178B2Methods and compositions comprising a KRas<sup>G12C </sup>inhibitor and a VEGF inhibitor for treating solid tumors

Publication Date: 2025.09.09 GENENTECH INC

AI summary

Provided herein are combination therapies comprising a KRasG12C inhibitor (e.g. Compound 1 or a pharmaceutically acceptable salt thereof) and a VEGF antagonist (e.g., bevacizumab) and methods of using such combination therapies.