Background: Somatic mutations in the epidermal growth factor receptor (EGFR) are detected in nearly 15% of patients with lung adenocarcinoma. These mutations are critical for tumor development and maintenance; some but not all are sensitive to EGFR tyrosine kinase inhibitors (TKI). EGFR mutations fall into 3 major categories: 1) Exon 19 deletions and L858R which are detected in 85% of patients; 2) Atypical EGFR mutations including G719X, L861Q which are detected in 5 to 8% of patients and 3) Exon 20 insertion mutations which are also detected in 5 to 8% of patients. These different subtypes exhibit varying responses to TKI treatment, with osimertinib being the standard of care for patients with exon 19 deletion or L858R mutations. However, no currently-approved TKI is available for patients with Exon 20/EGFR mutant lung cancer.

Method: Patient advocacy groups representing oncogene-driver mutations in lung cancer (ALK, EGFR, Exon 20, RET, ROS1) have assembled with the objectives of providing patient education/support and driving research into lung cancer’s causes and treatments. The EGFR Resisters represent over 775 patients from 26 countries. In an effort to understand mechanisms of resistance and develop new treatments, EGFR Resisters embarked on a collaboration with Dr. Pasi Jänne, the Addario Lung Cancer Medical Institute, the Bonnie J. Addario Lung Cancer Foundation, and Champions Oncology to develop patient-derived xenograft (PDX) models for EGFR mutant lung cancer.

Result: In mid-2018 the EFGR Resisters assembled a coalition of key leaders in the lung cancer space to advance development of research models for EGFR mutant lung cancer. The IRB-approved study, “A Prospective Biospecimen Collection Study from Patients with EGFR mutant Tumors” was launched in November 2018 with a goal of developing at least ten EGFR mutant PDX models with full characterization including whole exome sequencing (WES) and RNA sequencing. Model development will be divided among three cohorts: 1) EGFR T790M patients who have progressed on osimertinib or other third-generation TKIs; 2) EGFR exon 19 del or L858R patients who have progressed on first-line osimertinib; 3) patients with Exon 20 insertion mutations (includes EGFR Exon 20 and HER2 Exon 20). The models will be made available to the scientific community.

Conclusion: Understanding mechanisms of resistance in EGFR mutant lung cancer is high priority as most patients will ultimately develop resistance to currently-approved TKIs. Additionally, there is an urgent need to develop next-generation TKIs since some EGFR mutation subtypes do not respond to current therapies. By leveraging the skills and expertise of diverse partners, the EGFR Resisters have advanced an initiative to create a unique cohort of PDX models that will provide a rich resource for clinical and translational research to understand mechanisms of resistance and develop new therapies for patients with EGFR mutant lung cancer.

Citation Format: Ivy B. Elkins, Jill Feldman, Anita Figueras, Teri Kennedy, Allen Lee, Ildiko Medve, Colleen Sturdivant, Pasi Janne, Tony Addario, Alicia Sable-Hunt, Bonnie Addario, David LeDuc, Amy Moore, Jennifer Jaskowiak, Maria Mancini. A prospective biospecimen collection study from patients with EGFR mutant tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4744.