A phase II trial of defactinib and VS-6766 in diffuse gastric cancer

Summary:

Globally there are over 1 million cases and nearly 780,000 deaths from gastric cancer each year. ​The long-term survival rates for patients with advanced disease remain abysmal with less than 5% alive at 5-year from diagnosis. There are currently no therapies for diffuse type gastric cancer which represents a third of new gastric cancer diagnoses. There is a lack of conventional oncoproteins that are mutated in diffuse gastric cancer which hinders the development of targeted therapies. Thus, there is a large unmet clinical need and scientific knowledge gap. ​Additionally, there are large disparities when it comes to gastric cancers. Hispanic and black patients are almost twice as likely to develop gastric cancer and die of the disease than non-Hispanic whites. Furthermore, Hispanics are more often diagnosed with advanced stage disease.​ In preclinical models, it has been discovered that the protein FAK is highly active in diffuse gastric cancers and drives tumor progression. ​Additionally, preclinical models found that inhibiting the FAK protein stopped tumor growth. However, using a drug that targeted FAK alone led to compensatory uncontrolled growth of cancer cells through the MAPK pathway. Fortunately, this could be overcome by combining a FAK targeting drug with a drug that targets the protein MEK, a vital step in MAPK pathway. ​This phase II trial will assess the overall response rate of defactinib (a FAK targeting agent) with VS-6766 (RAF/MEK targeting drug) in patients with advanced diffuse gastric cancer. To their knowledge, this trial will be one of the first studies to evaluate a targeted treatment regimen selectively for diffuse gastric cancer.

Trial Registration: ClinicalTrials.gov Identifier: NCT06487221