CHRYSALIS-2: Amivantamab in EGFR Exon 20 Insertion NSCLC

Background

Real-world comparative cohort study referencing the CHRYSALIS phase I program of amivantamab (bispecific EGFR/MET antibody) in EGFR exon 20 insertion-mutated NSCLC progressing on platinum-based chemotherapy. Taiwan real-world comparison cohort (n=44) vs CHRYSALIS amivantamab cohort (n=114).

Interventions and follow up

Arm A: Amivantamab (CHRYSALIS trial protocol)
Arm B: Real-world therapies (non-platinum chemotherapy, TKIs)
Primary endpoint: PFS, time to next treatment, ORR, OS
mFollow up: NR (median PFS/OS reported)

Results

PFS: 6.9 mo (amivantamab) vs 2.3 mo (real-world), P<.0001
Time to next treatment: 12.2 vs 3.5 mo, P<.0001
ORR: 36.8% vs 3.0%, P<.00001
OS: median 23.1 vs 7.5 mo, P=.0005 (propensity-score adjusted)

Adverse events

Dermatologic: rash typical of EGFR inhibition
Infusion: infusion-related reactions common (mostly grade 1–2)
Gastrointestinal: diarrhea
Other: grade ≥3 rates manageable in phase I setting

Conclusions

Amivantamab demonstrates substantial benefit over real-world second-line therapies in EGFR exon 20-mutated NSCLC; addresses significant unmet need in this population with limited targeted options.

Key Limitations

Observational comparison; real-world cohort not randomized; institutional and selection bias possible; small Taiwan cohort (n=44); CHRYSALIS enrolled globally but comparison to a Taiwan subset may not generalize. Cross-trial comparison rather than head-to-head randomization.

Clinical Context

EGFR exon 20 insertions comprise ~1–2% of EGFR+ NSCLC and are historically resistant to standard TKIs. FDA and EMA approved amivantamab for platinum-pretreated EGFR exon 20 insertion NSCLC based on CHRYSALIS, a major therapeutic advance for this genotype. Per ASCO and ESMO, amivantamab (or mobocertinib historically) is a preferred targeted option in this setting. CHRYSALIS-2 and ongoing trials refine dosing and combinations.

References