Background
Phase II (POSITION20); N=25 EGFR exon20 insertion+, T790M-negative NSCLC (48% treatment-naïve); single-arm.
Interventions and follow up
Treatment: Osimertinib 160 mg PO daily
Primary endpoint: overall response rate (ORR)
mFollow up: NR
Primary endpoint: overall response rate (ORR)
mFollow up: NR
Results
ORR: 28%
mDoR: 5.3mo
mPFS: 6.8mo
mOS: 15.2mo
mDoR: 5.3mo
mPFS: 6.8mo
mOS: 15.2mo
Adverse events
Gastrointestinal: diarrhea 72%.
Dermatologic: dry skin 44%.
Constitutional: fatigue 44%.
Dermatologic: dry skin 44%.
Constitutional: fatigue 44%.
Conclusions
High-dose osimertinib (160 mg) demonstrated modest activity in EGFR exon20 insertion+ NSCLC.
Key Limitations
Small single-arm phase II (N=25); no comparator; modest, short-lived responses; heterogeneous prior-treatment status.
Clinical Context
Standard osimertinib is poorly active against EGFR exon20 insertions. ESMO favors exon20-directed agents (amivantamab) or platinum chemo; high-dose osimertinib is not a guideline-endorsed standard.