Johnson & Johnson: RYBREVANT + LAZCLUZE yields 41‑month median OS in first‑line atypical EGFR‑mutant NSCLC
- CHRYSALIS-2 cohort C (n=49) evaluated IV amivantamab (RYBREVANT, Janssen) plus oral lazertinib (LAZCLUZE; Janssen/Yuhan) as first-line therapy for atypical EGFR-mutant advanced NSCLC
- Efficacy: ORR 57%; median OS 41.0 months (95% CI 27.7–NE) with 3-yr OS 55% and 4-yr OS 46% at median follow-up 31.3 months; common atypical mutations were G719X 55%, S768X 27%, L861X 24%, and 35% had multiple atypical mutations; 41% remained on RYBREVANT ≥2 years
- Safety: most TEAEs were Grade 1-2—paronychia 78%, rash 65%, hypoalbuminemia 61%, infusion-related reactions 61%—and the combination carries VTE and ILD/pneumonitis risks, with prophylactic anticoagulation advised for the first four months
Study overview
CHRYSALIS-2 is an open-label Phase 1/1b evaluating IV amivantamab plus oral lazertinib; Cohort C tested this combination as first-line therapy in atypical EGFR‑mutated advanced NSCLC (excluding exon 20 insertions); cohort C included 49 patients and the overall study enrolled 460; patients were treatment‑naïve or had up to two prior lines.
Patient and mutation profile
Common atypical mutations were G719X (55%), S768X (27%) and L861X (24%); 35% of patients had multiple atypical mutations; analyses included subgroups with CNS metastases and different TP53 status.
Efficacy
Objective response rate was 57% (previously reported); at median follow‑up 31.3 months median overall survival was 41.0 months (95% CI 27.7–not estimable); estimated OS was 55% at three years and 46% at four years; 41% remained on amivantamab ≥2 years; consistent activity was observed across mutation subgroups and baseline characteristics.
Safety
Safety was consistent with prior reports and mostly Grade 1–2 events; common treatment‑emergent events (>30%) included paronychia (78%), rash (65%), hypoalbuminemia (61%) and infusion‑related reactions (61%); notable risks include interstitial lung disease/pneumonitis and venous thromboembolism, with recommendations to monitor and consider prophylactic anticoagulation during the first four months of treatment.
Source: J&J