Johnson & Johnson Combo Delivers 41-Month Median OS, 55% Three-Year Rate in NSCLC
JNJ•Johnson & Johnson’s Phase 1/1b CHRYSALIS-2 study reported a median overall survival of 41.0 months for first-line RYBREVANT plus LAZCLUZE in atypical EGFR-mutated NSCLC, with 55% three-year and 46% four-year OS rates. 41% of patients remained on treatment at least two years, with mostly Grade 1-2 adverse events.
1. CHRYSALIS-2 Study Design and Patient Cohort
The Phase 1/1b CHRYSALIS-2 trial evaluated RYBREVANT plus LAZCLUZE as first-line therapy in 49 patients with advanced NSCLC harboring atypical EGFR mutations. Exon 20 insertions and common exon 19/L858R mutations were excluded. The cohort included G719X (55%), S768X (27%) and L861X (24%) mutations, with 35% of patients carrying multiple atypical alterations.
2. Efficacy Outcomes
The combination achieved a 57% objective response rate and a median overall survival of 41.0 months (95% CI, 27.7–not estimable) at a 31.3-month follow-up. Survival rates reached 55% at three years and 46% at four years, while 41% of patients remained on treatment for two years or longer, indicating durable benefit.
3. Safety Profile
Treatment-emergent adverse events were primarily Grade 1 or 2, with paronychia in 78% of patients, rash in 65%, hypoalbuminemia in 61% and infusion-related reactions in 61%. No new safety signals emerged with extended follow-up.
4. Strategic Implications and Next Steps
These long-term outcomes address a significant unmet need in atypical EGFR-mutated NSCLC and reinforce the potential of dual EGFR/MET targeting. Johnson & Johnson plans further pivotal trials and regulatory submissions to support first-line approval of the RYBREVANT plus LAZCLUZE regimen.
