On August 8, 2022 Guardant Health Inc. (Nasdaq: GH), a leading precision oncology company, and Blueprint Medicines Corporation (Nasdaq: BPMC) reported they are presenting new data demonstrating that the EGFR C797X mutation is the most common resistance mechanism to osimertinib therapy for patients with advanced non-small cell lung cancer (NSCLC) (Press release, Guardant Health, AUG 8, 2022, View Source [SID1234617805]). The results are being reported today at the International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer in Vienna.

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"This real-world study improves our understanding of how resistance mutations to osimertinib emerge over time, with new insights on when EGFR C797X mutations overtake MET amplifications as the most commonly acquired resistance mechanism," said Suresh Ramalingam, M.D., FACP, FASCO, executive director of Winship Cancer Institute of Emory University, who served as the principal investigator for the study. "The analysis characterizes the increased frequency of EGFR C797X mutations as patients are treated with first-line osimertinib for longer durations, reinforcing the need for next-generation EGFR inhibitors to address C797X-driven resistance."

A collaborative effort between Guardant Health, Blueprint Medicines and Winship Cancer Institute, the study analyzed de-identified clinical and genomic data using the GuardantINFORM real-world evidence platform, which includes more than 65,000 adults with advanced NSCLC. The analysis evaluated genomics data from the Guardant360 circulating tumor DNA (ctDNA) test for more than 2,000 patients who had any EGFR mutation and treatment with osimertinib, a third-generation EGFR TKI (tyrosine kinase inhibitor) and the current standard of care for patients with advanced-stage NSCLC with common EGFR mutations. The study incorporated ctDNA results up to five years after patients initiated osimertinib therapy.

Cumulatively, the analysis indicated that EGFR C797X mutations were 1.25 times more common than MET amplification when osimertinib was used as first-line therapy and 2.4 times more common when it was used as second-line therapy. In patients likely to experience disease progression after first-line treatment with osimertinib, the cumulative incidence of EGFR C797X mutations was 12.5 percent. MET amplifications were the most common resistance mutation in the first year of osimertinib treatment, and EGFR C797X mutations exceeded the rate of MET amplifications in years two through five.

"This study is an excellent example of how real-world data from the GuardantINFORM platform can be used to shed new light on resistance mechanisms in lung cancer therapy," said Helmy Eltoukhy, Guardant Health chairman and co-CEO. "The analysis provided critical insights about resistance mutations that can contribute to the development of more effective therapies for lung cancer."

"We are committed to developing transformative precision therapies that prevent or overcome treatment resistance, which represents an important medical need for patients with EGFR-mutant, non-small cell lung cancer," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "Our collaboration with Guardant Health advances our efforts to characterize dynamic treatment resistance patterns in lung cancer, helping inform therapeutic strategies, including novel combinations, that may prolong patient benefit."

Blueprint_Logo_RGB_full-color (1).jpg Guardant Health

About GuardantINFORM
The GuardantINFORM clinical-genomic platform is intended to help accelerate research and development of the next generation of cancer therapeutics by offering biopharma partners an in-silico platform that combines de-identified longitudinal clinical information and genomic data collected from the Guardant360 liquid biopsy test. With data from more than 225,000 patients diagnosed with locally advanced and metastatic cancers, this robust dataset offers real-world insights into anti-cancer therapy use in the clinic, tumor evolution, and treatment resistance throughout each patient’s treatment journey for many advanced solid tumor cancers, including non-small cell lung, breast, colon and prostate.