1264P - Real-world evidence of treatment practices and therapeutic outcomes for newly diagnosed NSCLC patients with non-classical EGFR mutations demonstrates high unmet medical need

Background

Widespread adoption of tumor sequencing in NSCLC patients has revealed a broad spectrum of oncogenic EGFR non-classical mutations (NCMs), including PACC (P loop and αC helix compressing) and other groups, in addition to classical mutations L858R and Ex19del.

Methods

Analysis of 11,434 sequenced cases of newly diagnosed and treatment naïve EGFRm NSCLC within the GuardantINFORM^tm clinical-genomic database (1L treatment information in 3,276 patients) reveals a broad spectrum of NCMs and allows association of discrete groups of mutations with real-world treatment practices and therapeutic outcomes.

Results

There are greater than 100 validated oncogenic EGFR mutations expressed in NSCLC. NCMs comprise at least 22% of newly diagnosed EGFRm NSCLC and can be cohesively grouped into families based on structural properties and pharmacology. Treatment practices for patients with NCMs remain heterogenous: 36% of patients received osimertinib or afatinib and 60% of patients received chemotherapy and/or immunotherapy. Preclinical data demonstrated weaker potency for osimertinib against NCMs compared with classical mutations, and patients expressing NCMs discontinue osimertinib sooner than patients expressing classical mutations. L858R patients with NCM co-expression discontinue osimertinib therapy sooner than patients expressing L858R alone.

Conclusions

Compared to NSCLC patients expressing classical EGFR mutations, patients expressing NCMs discontinue EGFR inhibitor treatment sooner, and chemotherapy remains the most common treatment, with poor patient outcomes. Moreover, the co-expression of osimertinib-resistant NCMs with L858R may contribute to inferior outcomes versus patients with L858R alone. These real-world data underscore the unmet medical need of patients expressing NCMs, and the opportunity for a 4^th-generation TKI that potently inhibits NCMs in the newly diagnosed setting. Table: 1264P

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Black Diamond Therapeutics.

Funding

Black Diamond Therapeutics.

Disclosure

J.V. Heymach, M. Nilsson, Y.Y. Elamin, X. Le: Financial Interests, Institutional, Research Funding: BDTX. E. Dardenne, C. Guzman, S. Eathiraj, E. Buck: Financial Interests, Institutional, Full or part-time Employment: BDTX. J. Liao, N. Zhang: Financial Interests, Institutional, Full or part-time Employment: GH.