TMB-Guided Immunotherapy Selection for Gastroesophageal Cancer
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need to identify groups of patients with gastroesophageal cancer who have comparable or superior outcomes on immune checkpoint inhibitor monotherapy compared to ICPI with chemotherapy, as direct outcome comparisons in phase III clinical trials are limited.
Innovation Solution
Determine a tumor mutational burden (TMB) score for a biopsy sample from an individual with gastroesophageal cancer and administer an immune checkpoint inhibitor without chemotherapy if the TMB score is at or higher than a threshold, or with chemotherapy if the TMB score is below the threshold.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint inhibitor monotherapy is used, then treatment efficacy and survival outcomes are improved for high TMB patients, but treatment options are limited for low TMB patients who require chemotherapy combination
Solution Approach 1:
The patent applies local quality by tailoring the treatment approach to the specific TMB characteristics of each patient group. High TMB patients receive ICPI monotherapy to maximize survival benefits, while low TMB patients receive ICPI-chemotherapy combination therapy to address their different biological needs. This localized treatment strategy optimizes outcomes for each subgroup rather than applying a uniform approach.
Solution Approach 2:
The patent utilizes parameter changes by using TMB score as a critical parameter to determine treatment selection. By measuring and comparing TMB scores against established thresholds, the system dynamically adjusts the treatment regimen (monotherapy vs. combination therapy) based on the measured parameter value, enabling adaptive treatment decisions that improve both reliability and versatility.
2Loss of time
If TMB scoring is performed on small biopsy samples, then diagnostic speed is improved, but measurement precision may be compromised due to limited tissue availability
Solution Approach 1:
The patent applies preliminary action by performing TMB scoring on small biopsy samples obtained during initial diagnostic procedures. This allows TMB status to be determined early in the treatment decision-making process, enabling rapid treatment selection without requiring additional time-consuming procedures. The preliminary TMB assessment on available biopsy material guides immediate treatment planning.
Solution Approach 2:
The patent utilizes copying by creating comprehensive TMB assessments from limited biopsy material through next-generation sequencing techniques. The sequencing process generates multiple data copies and comprehensive mutational profiles from the small sample, effectively amplifying the information content available from limited tissue and maintaining measurement precision despite small sample size.
Data Source
AI summary
Disclosed herein are methods of treating an individual having a gastroesophageal cancer, of treating or identifying an individual having gastroesophageal cancer for a treatment, or stratifying individuals having a gastroesophageal cancer for a treatment based on a tumor mutational burden (TMB) score or a TMB score.