KRasG12C Combination Therapy Without PI3KCA Pretesting

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Solution Overview

Problem

There is a need for effective therapies, including combination therapies, to treat cancers such as lung cancer, colorectal cancer, and pancreatic cancer harboring KRasG12C mutations, as current treatments provide limited benefit for advanced stage KRasG12C-positive tumors.

Innovation Solution

A combination therapy comprising GDC-6036, a KRasG12C inhibitor, and inavolisib, a PI3K inhibitor, administered daily for multiple cycles, without the need for pretesting for PI3KCA mutations, to treat cancers with KRasG12C mutations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If combination therapy with GDC-6036 and inavolisib is used to treat KRasG12C-positive cancers, then therapeutic efficacy is improved, but treatment complexity increases

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidtreatment complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines two therapeutic agents (GDC-6036, a KRasG12C inhibitor, and inavolisib, a PI3K inhibitor) into a single combination therapy regimen. This merging of multiple treatment mechanisms targets both the KRasG12C mutation and the PI3K pathway simultaneously, thereby improving therapeutic efficacy through synergistic action while managing the complexity through coordinated administration protocols

Inventive Principle:

Principle #5Merging (Combining)

2Measurement precision

If pretesting for PI3KCA mutations is required before administering inavolisib, then treatment precision is improved, but treatment time is increased

Engineering Contradiction:

Improvetreatment precisionVSAvoidtreatment time

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent establishes a universal treatment protocol where inavolisib can be administered in combination with GDC-6036 to patients with KRasG12C-positive cancers regardless of their PI3KCA mutation status. This multi-functional approach allows the combination therapy to be effective both in patients with PI3KCA mutations and those without, thereby eliminating the need for separate pretesting and reducing treatment initiation time while maintaining therapeutic precision through the coordinated action of both agents

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20260053802A1TREATMENT OF CANCER USING COMBINATION THERAPIES COMPRISING GDC-6036 and GDC-0077

Publication Date: 2026.02.26 GENENTECH INC

AI summary

Provided herein are combination therapies comprising GDC-6036 and inavolisib and methods of using the same to treat cancer.