WCLC 2025 - Posters & ePosters-P3.18.69 Efficacy and Safety of Befotertinib Plus Icotinib in Advanced NSCLC With Uncommon EGFR Mutations: A Phase II Study (Icombine)

P3.18.69 Efficacy and Safety of Befotertinib Plus Icotinib in Advanced NSCLC With Uncommon EGFR Mutations: A Phase II Study (Icombine)

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This Phase II, single-arm trial (IcomBine; NCT06517953) evaluates the efficacy and safety of combining befotertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), with icotinib, a first-generation EGFR-TKI, in treatment-naïve patients with advanced non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutations (G719X, L861Q, S768I). These uncommon mutations account for 10-15% of EGFR-mutant NSCLC and currently lack a standardized optimal therapy, as most targeted treatments focus on classical EGFR mutations like exon 19 deletions and exon 21 L858R. <br /><br />The study employs Simon’s two-stage design, initially enrolling 8 patients who receive befotertinib 75 mg once daily plus icotinib 125 mg three times daily. Dose escalation of befotertinib to 100 mg is permitted after 21 days if no significant toxicity (grade 2 thrombocytopenia or headache) occurs. If at least 2 patients respond, an additional 15 patients will be enrolled (total n=23). Treatment continues until disease progression, unacceptable toxicity, or withdrawal. <br /><br />Primary endpoint is objective response rate (ORR) by RECIST v1.1; secondary endpoints include progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Patient enrollment is ongoing. <br /><br />Background highlights that while approved EGFR-TKIs like afatinib and osimertinib show some efficacy in uncommon EGFR mutations, the optimal strategy is unclear. Prior studies suggest combining EGFR-TKIs of different generations (e.g., osimertinib plus gefitinib) can delay resistance with high response rates, but this approach remains untested for uncommon mutations. Befotertinib has previously demonstrated superior PFS versus icotinib in classical EGFR-mutant NSCLC.<br /><br />This study aims to fill the unmet need by assessing whether the befotertinib and icotinib combination improves outcomes and is safe for patients with advanced NSCLC bearing uncommon EGFR mutations.

Asset Subtitle

Xue Hou

Meta Tag

Speaker Xue Hou

Topic Clinical Trials in Progress

Keywords

Phase II trial

befotertinib

icotinib

EGFR tyrosine kinase inhibitor

non-small cell lung cancer

uncommon EGFR mutations

G719X

L861Q

S768I

objective response rate