Skip to content

CHRYSALIS-2 (Cohort C) — Amivantamab + lazertinib, first-line atypical EGFR-mutated advanced NSCLC

Abstract: 8501 · Session: Lung Cancer—Non-Small Cell Metastatic (oral), 2026 ASCO Annual Meeting, Chicago · Presenter: Joel W. Neal, MD, PhD (Stanford Cancer Institute) · Embargo: per ASCO

At a glance

  • Sponsor: Janssen Research & Development (Johnson & Johnson)
  • PI / presenter: Joel W. Neal, MD, PhD — Stanford Cancer Institute, Palo Alto, CA
  • NCT ID: NCT04077463
  • Phase: 1/1b
  • Design: Open-label, single-arm cohort (Cohort C of CHRYSALIS-2) — first-line amivantamab IV + oral lazertinib in treatment-naïve atypical EGFR-mutated advanced NSCLC
  • N: 49 (treatment-naïve, atypical EGFR mutations)
  • Primary endpoint(s): ORR (investigator-assessed); key secondary OS, PFS, DOR, safety
  • Comparator: None (single-arm)
  • Indication: Advanced NSCLC with atypical (non-classical) EGFR mutations — G719X, S768I, L861Q, and compound mutations
  • Line: First-line

Headline result

At a median follow-up of 31.3 months (data cutoff Oct 31, 2025), first-line amivantamab + lazertinib produced a median OS of 41.0 months (95% CI, 27.7–NE) in 49 treatment-naïve patients with atypical EGFR-mutated advanced NSCLC. Landmark OS rates were 85% at 12 months, 72% at 24 months, and 55% at 36 months, with 46% of patients alive at 4 years. Investigator-assessed ORR was 57% and median PFS 19.5 months (95% CI, 11.2–NE). Mutation distribution included G719X (55%), S768I/S768X (27%), and L861Q/L861X (24%), with compound mutations in 35%. The presenter reported durable responses across demographic and tumor subgroups with no new safety signals on longer follow-up. As a single-arm cohort there is no comparator HR or p-value.

Mechanism / class

Amivantamab (Rybrevant) is a bispecific EGFR × MET antibody; lazertinib (Lazcluze) is a third-generation EGFR TKI. The combination is approved in the US/EU for first-line classical EGFR-mutant (exon 19 del / L858R) advanced NSCLC (MARIPOSA). Cohort C extends the regimen to atypical EGFR mutations, a subgroup historically associated with worse outcomes on classical EGFR TKIs than exon 19 del or L858R disease.

Practice-changing?

Pending. Best reported survival to date in an uncommon, hard-to-treat EGFR subgroup with limited prospective data, but the evidence is a single-arm, 49-patient cohort without a randomized comparator. Supports amivantamab + lazertinib as a viable first-line option for atypical EGFR-mutant NSCLC and strengthens the rationale for a dedicated randomized/registrational study; not by itself a new standard.

Sources

  • ASCO Meeting Library (Abstract 8501): https://meetings.asco.org/abstracts-presentations/search?q=8501
  • OncLive: https://www.onclive.com/view/amivantamab-plus-lazertinib-produces-clinically-meaningful-os-in-atypical-egfr-mutated-advanced-nsclc
  • CancerNetwork: https://www.cancernetwork.com/view/amivantamab-regimen-boosts-survival-in-egfr-nsclc-subtype
  • J&J press release: https://www.jnj.com/media-center/press-releases/rybrevant-amivantamab-vmjw-plus-lazcluze-lazertinib-demonstrates-prolonged-clinical-benefit-as-a-first-line-treatment-for-atypical-egfr-mutated-non-small-cell-lung-cancer
  • Prior data (JCO, CHRYSALIS-2): https://ascopubs.org/doi/10.1200/JCO-24-02835