Johnson & Johnson (NYSE: JNJ) reported updated results from the Phase 1/1b CHRYSALIS-2 study evaluating RYBREVANT plus LAZCLUZE as first-line treatment for patients with advanced non-small cell lung cancer harboring atypical EGFR mutations. The combination achieved a median overall survival of nearly 3.5 years (41.0 months) in this patient population.

The study enrolled 49 patients with atypical EGFR-mutated advanced NSCLC, excluding EGFR exon 20 insertion mutations. The most common atypical EGFR mutations included G719X (55%), S768X (27%) and L861X (24%), with 35% of patients harboring multiple atypical mutations. The previously reported objective response rate was 57%.

Overall survival rates were 55% at three years and 46% at four years. Clinical activity was observed across atypical EGFR mutation subgroups and patient characteristics. Notably, 41% of patients remained on RYBREVANT for two years or longer.

Atypical EGFR mutations represent approximately 10-20% of all EGFR-mutated cases and are associated with poorer outcomes than common EGFR mutations. Median overall survival with current standard therapies remains under two years for this population.

The safety profile was consistent with previous reports, with no new safety signals observed. Most adverse events were Grade 1 or 2. The most common treatment-emergent adverse events occurring in more than 30% of patients included paronychia (78%), rash (65%), hypoalbuminemia (61%) and infusion-related reactions (61%).

The results were presented at the 2026 American Society of Clinical Oncology Annual Meeting. RYBREVANT-based regimens are already approved for patients with EGFR-mutated advanced NSCLC across common and exon 20 insertion mutations in the first-line setting.