EGFR T790M

After resolution with corticosteroids, treatment was switched to afatinib. This study highlights the heterogeneous approaches to OILI and the potential feasibility of rechallenge in selected patients. Given the expanding osimertinib use for early and advanced stage NSCLC, further research is warranted to refine treatment decisions and optimize patient safety.

P1/2, N=37, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

P1, N=105, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2026 --> Oct 2026 | Trial primary completion date: Mar 2026 --> Oct 2026

P2, N=42, Active, not recruiting, AIO-Studien-gGmbH | Trial completion date: Dec 2026 --> Mar 2027

Compound 19 was the most potent inhibitor of WT EGFR (3.0 nM) observed, more potent than the EGFR WT inhibitor Erlotinib (5.9 nM). Compounds 48 and 49 demonstrated better activity for the double-mutant EGFR (3.0 & 2.0 nM, respectively) than Osimertinib (12.8 nM)...Kinetic evaluation of 48 (propenamide moiety) vs 49 (acrylamide electrophile) confirms kinact/Ki values consistent with a covalent mode of action for the latter, but not the former. 2009 Elsevier Ltd.

P2, N=171, Completed, AstraZeneca | Active, not recruiting --> Completed

P3, N=744, Recruiting, AstraZeneca | Active, not recruiting --> Recruiting

The addition of osimertinib to curative-intent strategies have demonstrated improvements in disease-free survival and overall survival (OS) as adjuvant therapy in resected stage IB-IIIa patients, major pathological responses compared to chemotherapy when used as neoadjuvant therapy, and progression-free survival (PFS) compared to placebo when used as consolidation therapy in unresectable stage III patients. Currently, subsequent treatment recommendations include chemotherapy or datopotamab deruxtecan following progression on a third-generation EGFR-TKI combination and amivantamab plus platinum-based chemotherapy following progression on monotherapy. The treatment landscape for NSCLC with common EGFR mutations is rapidly evolving and third-generation EGFR-TKIs play an integral role in both the curative-intent and palliative settings.

P2, N=60, Not yet recruiting, Jonsson Comprehensive Cancer Center

P2, N=15, Not yet recruiting, Hunan Cancer Hospital

The patient eventually developed resistance to both first-line gefitinib and later almonertinib...He received ivonescimab monotherapy, achieving disease control for nearly 5 months before transitioning to ivonescimab plus pemetrexed with continued benefit and a manageable safety profile. This case illustrates the potential benefit of ivonescimab in patients with EGFR-mutant LUAD and baseline MPE who develop complex, non-canonical resistance to EGFR-TKIs. These findings support further clinical evaluation of ivonescimab in this poor-prognosis subgroup and highlight the importance of repeated molecular profiling in guiding treatment strategy.

CfDNA sampling from pleural effusion is a less invasive and more effective method for genomic profiling in NSCLC with disease progression, offering valuable insights to guide personalized treatment strategies.