Treatment outcomes in patients (pts) with advanced/metastatic non-small cell lung cancer (NSCLC) harboring MET amplification as a secondary oncogenic driver

e21056 Background: There is limited published evidence on the treatment outcomes of pts with oncogene driven NSCLC who have developed resistance to targeted therapies or novel therapies such as immune checkpoint inhibitors (ICIs) and have MET amplification ( METamp). METamp has been identified as a secondary driver of EGFR TKI resistance. We report here on real-world (rw) outcomes for these pts. Methods: A non-interventional, descriptive cohort study design was applied using ConcertAI electronic medical record data derived from US community oncology centers and linked with ASCO/CancerLinQ data. Eligible pts had stage IIIB–IV NSCLC, and METamp. Study period: Jan 1, 2004 – Oct 31, 2021. Subgroup analyses included 1: pts with oncogene driven NSCLC who received targeted therapy or ICIs after diagnosis of advanced NSCLC, then progressed and had a positive test for METamp, and 2: pts from subgroup 1 who received an EGFR TKI after diagnosis of advanced NSCLC, then progressed and had a positive test for METamp. The presence of METamp after progression on a therapy was hypothesized to indicate METamp as a secondary driver of resistance. Outcomes were analyzed for pts who received a subsequent line of systemic therapy after progression. Results: Of 8,454 pts with lung cancer and minimum 1 molecular test including MET alterations, 164 had METamp (1.9%) and were included in the study cohort. In subgroup 1, 35 pts had METamp detected (21.3%) after disease progression on a targeted therapy or ICIs (EGFR TKI n = 17, ICIs n = 11, other n = 7). Of those pts, 27 received a subsequent systemic therapy after disease progression. The rw overall response rate (ORR) was 18.5% (95% CI: 6.3, 38.1), the median rw progression-free survival (PFS) was 2.2 months (95% CI: 1.6, 4.2) and the median overall survival (OS) from start of the subsequent therapy was 11.3 months (95% CI: 3.4, 21.3). In subgroup 2, 17 pts had METamp detected after disease progression on an EGFR TKI (erlotinib or afatinib n = 13, osimertinib n = 4). Of those pts, 15 received a subsequent systemic therapy after disease progression. The rw-ORR was 13.3% (95% CI: 1.7, 40.5), median rw-PFS was 2.1 months (95% CI: 1.1, 4.6), and median OS from start of the subsequent therapy was 8.5 months (95% CI: 1.7, 15.2). Conclusions: METamp as a secondary driver of resistance is a new target for systemic therapy in pts with EGFR-mutant NSCLC who have developed resistance to EGFR TKIs. Overcoming this resistance using combinations with MET inhibitors is currently under investigation in several clinical trials. The analyses reported here suggests that the treatments available and current standard of care result in poor outcome for pts with METamp, highlighting the high medical unmet need in this population.