Background
Phase I (CHRYSALIS); N=81 EGFR exon20 insertion+ NSCLC after progression on platinum-based chemotherapy; single-arm.
Interventions and follow up
Treatment: Amivantamab 1050 mg (1400 mg if ≥80 kg) IV weekly ×4 weeks, then every 2 weeks
Primary endpoint: ORR by investigator assessment
mFollow up: 9.7mo
Primary endpoint: ORR by investigator assessment
mFollow up: 9.7mo
Results
ORR: 40% (CR in 3 patients)
mDOR: 11.1mo
mPFS: 8.3mo
mDOR: 11.1mo
mPFS: 8.3mo
Adverse events
Any grade: rash 86%, infusion-related reactions 66%, paronychia 45%.
Grade ≥3: hypokalemia 5%, rash 4%, pulmonary embolism 4%, diarrhea 4%, neutropenia 4%.
Ocular: rare; refer to ophthalmology if symptomatic.
Grade ≥3: hypokalemia 5%, rash 4%, pulmonary embolism 4%, diarrhea 4%, neutropenia 4%.
Ocular: rare; refer to ophthalmology if symptomatic.
Conclusions
Amivantamab provided durable responses as a second-line option for EGFR exon20 insertion+ NSCLC.
Key Limitations
Single-arm phase I, no comparator; investigator-assessed ORR; modest N; high infusion-reaction rate requires management.
Clinical Context
Amivantamab received FDA accelerated approval (May 2021) for EGFR exon20 insertion+ NSCLC after platinum chemo. PAPILLON later established 1L amivantamab + chemo. ESMO endorses amivantamab in this subset. Amivantamab = EGFR-MET bispecific IgG1; infusion reactions cluster on day 1.
References